Campbell Biology

The Immune System 43

Figure 43.1  What triggered this attack by an immune cell on a clump of bacteria?

Key Concepts Recognition and Response

43.1 In innate immunity, recognition For a pathogen—a bacterium, fungus, virus, or other disease-causing agent—the
internal environment of an animal offers a ready source of nutrients, a protected
and response rely on traits setting, and a means of transport to new environments. From the perspective of a
common to groups of pathogens cold or flu virus, we are in many ways wonderful hosts. From our vantage point, the
situation is not so ideal. Fortunately, adaptations have arisen over the course of
43.2 In adaptive immunity, receptors evolution that protect animals against many pathogens.

provide pathogen-specific Dedicated immune cells in the body fluids and tissues of most animals specifi-
recognition cally interact with and destroy pathogens. In Figure 43.1, for example, an immune
cell called a macrophage (brown) is engulfing rod-shaped bacteria (green). Some
43.3 Adaptive immunity defends immune cells are types of white blood cells called lymphocytes (such as the one
shown below with bacteria). Most lymphocytes recognize and respond to specific
against infection of body fluids types of pathogens. Together, the body’s defenses make up the immune system,
and body cells which enables an animal to avoid or limit many infections. A foreign molecule or
cell doesn’t have to be pathogenic to elicit an immune response, but we’ll focus in
43.4 Disruptions in immune system this chapter on the immune system’s role in defending against pathogens.

function can elicit or exacerbate The first lines of defense offered by immune systems help prevent pathogens
disease from gaining entrance to the body. For example, an outer covering, such as a skin or
shell, blocks entry by many pathogens. Sealing off the entire body surface is impos-
sible, however, because gas exchange, nutrition, and reproduction require openings

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950

to the environment. Secretions that trap or kill pathogens In adaptive immunity, molecular recognition relies
guard the body’s entrances and exits, while the linings of the on a vast arsenal of receptors, each of which recognizes a fea-
digestive tract, airway, and other exchange surfaces provide ture typically found only on a particular part of a particular
additional barriers to infection. molecule in a particular pathogen. As a result, recognition
and response in adaptive immunity occur with remarkable
If a pathogen breaches barrier defenses and enters specificity.
the body, the problem of how to fend off attack changes
substantially. Housed within body fluids and tissues, the The adaptive immune response, also known as the
invader is no longer an outsider. To fight infections, an ani- acquired immune response, is activated after the innate
mal’s immune system must detect foreign particles and cells immune response and develops more slowly. As reflected by
within the body. In other words, a properly functioning the names adaptive and acquired, this immune response is
immune system distinguishes nonself from self. How is this enhanced by previous exposure to the infecting pathogen.
accomplished? Immune cells produce receptor molecules Examples of adaptive responses include the synthesis of
that bind specifically to molecules from foreign cells or proteins that inactivate a bacterial toxin and the targeted
viruses and activate defense responses. The specific bind- killing of a virus-infected body cell.
ing of immune receptors to foreign molecules is a type of
molecular recognition and is the central event in identifying In this chapter, we’ll examine how each type of immu-
nonself molecules, particles, and cells. nity protects animals from disease. We’ll also investigate how
pathogens can avoid or overwhelm the immune system and
Two types of molecular recognition provide the basis how defects in the immune system can imperil health.
for the two types of immune defense found among animals:
innate immunity, which is common to all animals, and adap- Concept  43.1
tive immunity, which is found only in vertebrates. Figure 43.2
summarizes these two types of immunity, highlighting funda- In innate immunity, recognition
mental similarities and differences. and response rely on traits common
to groups of pathogens
In innate immunity, which includes barrier defenses,
molecular recognition relies on a small set of receptor pro- Innate immunity is found in all animals (as well as in plants).
teins that bind to molecules or structures that are absent from In exploring innate immunity, we’ll begin with inverte-
animal bodies but common to a group of viruses, bacteria, brates, which repel and fight infection with only this type of
or other pathogens. Binding of an innate immune receptor immunity. We’ll then turn to vertebrates, in which innate
to a foreign molecule activates internal defenses, enabling immunity serves both as an immediate defense against infec-
responses to a very broad range of pathogens. tion and as the foundation for adaptive immune defenses.

Figure 43.2  Overview of animal Pathogens Innate Immunity of Invertebrates
immunity. Innate immunity offers (such as bacteria,
a primary defense in all animals and fungi, and viruses) The great success of insects in terrestrial and freshwater habi-
sets the stage for adaptive immunity tats teeming with diverse pathogens highlights the effective-
in vertebrates. ness of invertebrate innate immunity. In any environment,
insects rely on their exoskeleton as a physical barrier against
INNATE IMMUNITY Barrier defenses: infection. Composed largely of the polysaccharide chitin,
(all animals) Skin the exoskeleton provides an effective barrier defense against
• Recognition of traits shared Mucous membranes most pathogens. Chitin also lines the insect intestine, where
Secretions it blocks infection by many pathogens ingested with food.
by broad ranges of Internal defenses: Lysozyme, an enzyme that breaks down bacterial cell walls,
pathogens, using a small Phagocytic cells further protects the insect digestive system.
set of receptors Natural killer cells
Antimicrobial proteins Any pathogen that breaches an insect’s barrier defenses
• Rapid response Inflammatory response encounters internal immune defenses. Insect immune cells
produce a set of recognition proteins, each of which binds
ADAPTIVE IMMUNITY Humoral response: to a molecule common to a broad class of pathogens. Many
(vertebrates only) Antibodies defend against of these molecules are components of fungal or bacterial cell
• Recognition of traits infection in body fluids. walls. Because such molecules are not normally found in
Cell-mediated response: animal cells, they function as “identity tags” for pathogen
specific to particular Cytotoxic cells defend recognition. Once bound to a pathogen molecule, a recogni-
pathogens, using a vast against infection in body cells. tion protein triggers an innate immune response.
array of receptors

• Slower response

chapter 43  The Immune System 951

The major immune cells of insects are called hemocytes. Figure 43.3  Phagocytosis. This diagram depicts events in the
Like amoebas, some hemocytes ingest and break down ingestion and destruction of pathogens by a typical phagocytic cell.
microorganisms, a process known as phagocytosis
(Figure 43.3). One class of hemocytes produces a defense Pathogen 1 Pseudopodia
molecule that helps entrap large pathogens, such as surround
Plasmodium, the single-celled parasite of mosquitoes that pathogens.
causes malaria in humans. Many other hemocytes release
antimicrobial peptides, which circulate throughout the body PHAGOCYTIC CELL 2 Pathogens
of the insect and inactivate or kill fungi and bacteria by are engulfed
disrupting their plasma membranes. Vacuole Lysosome by endocytosis.
containing
The innate immune response of insects is specific for par- enzymes 3 Vacuole
ticular classes of pathogens. For example, if a fungus infects forms,
an insect, binding of recognition proteins to fungal cell wall enclosing
molecules activates a transmembrane receptor called Toll. pathogens.
Toll in turn activates production and secretion of antimicro- 4 Vacuole
bial peptides that specifically kill fungal cells. Remarkably, and lysosome
phagocytic mammalian cells use receptor proteins very simi- fuse.
lar to the Toll receptor to recognize viral, fungal, and bacte-
rial components, a discovery that was recognized with the 5 Toxic
Nobel Prize in Physiology or Medicine in 2011. compounds
and lysosomal
Insects also have specific defenses that protect against infec- enzymes destroy
tion by viruses. Many viruses that infect insects have a genome pathogens.
consisting of a single strand of RNA. When the virus replicates 6 Debris from
in the host cell, this RNA strand is the template for synthesis of pathogens is
double-stranded RNA. Because animals do not produce double- released by
stranded RNA, its presence can trigger a specific defense against exocytosis.
the invading virus, as illustrated in Figure 43.4.

Figure 43.4  Antiviral defense in insects. In defending against an infecting RNA virus,
an insect cell turns the viral genome against itself, cutting the viral genome into small fragments
that it then uses as guide molecules to find and destroy viral messenger RNAs (mRNAs).

Viral infection Host defense Double-stranded viral RNA 1 The host enzyme Dicer-2
During infection, the single-stranded viral HOST CELL recognizes the double-
RNA genome is replicated. A double strand stranded RNA structure
of viral RNA forms briefly during replication. formed during the
replicative cycle of an RNA
RNA virus 1 Dicer-2 virus. Dicer-2 cuts the viral
enzyme RNA into fragments, each
21 nucleotides long.
HOST CELL
2 A protein complex
Viral RNA Single-stranded viral mRNA 2 Argo containing the host
genome protein enzyme Argo binds to an
complex RNA fragment, displacing
one of the two strands.

3 The Argo complex uses
the bound single-stranded
fragment as a guide,
3 matching it to the

VISUAL SKILLS Based on this figure and the complementary sequence
accompanying text, define the specificity of the Dicer-2 in a viral mRNA. Argo
then cuts the viral mRNA,
and Argo enzymes in terms of the size, number of inactivating it and thus
blocking synthesis of viral
strands, and sequence of the RNA molecules they proteins.

each bind or act upon.

952 unit seven  Animal Form and Function

Innate Immunity of Vertebrates EXTRACELLULAR Lipopolysaccharide
FLUID
In jawed vertebrates, innate immune defenses coexist with
the more recently evolved system of adaptive immunity. Helper TLR4 Flagellin
Because most discoveries regarding vertebrate innate immu- protein TLR5
nity have come from studies of mice and humans, we’ll
focus here on mammals. In this section, we’ll consider first PHAGOCYTIC CELL
the innate defenses that are similar to those found among
invertebrates: barrier defenses, phagocytosis, and antimi- CpG DNA
crobial peptides. We’ll then examine some unique aspects
of vertebrate innate immunity, such as natural killer cells, VESICLE TLR9 Innate immune
interferons, and the inflammatory response. responses

Barrier Defenses dsRNA

The barrier defenses of mammals, which block the entry of TLR3
many pathogens, include the mucous membranes and skin.
The mucous membranes that line the digestive, respiratory, Figure 43.5  TLR signaling. Each mammalian Toll-like receptor
urinary, and reproductive tracts produce mucus, a viscous (TLR) recognizes a molecular pattern characteristic of a group of
fluid that traps pathogens and other particles. In the airway, pathogens. Lipopolysaccharide, flagellin, CpG DNA (DNA containing
ciliated epithelial cells sweep mucus and any entrapped unmethylated CG sequences), and double-stranded (ds) RNA are all
material upward, helping prevent infection of the lungs. found in bacteria, fungi, or viruses but not in animal cells. Together
Saliva, tears, and mucous secretions that bathe various with other recognition and response factors, TLR proteins trigger
exposed epithelia provide a washing action that also inhib- internal innate immune defenses, including production of cytokines
its colonization by fungi and bacteria. and antimicrobial peptides.

Beyond their physical role in inhibiting microbial entry, VISUAL SKILLS Look at the locations of the TLR proteins and then
body secretions create an environment that is hostile to suggest a possible benefit of their distribution.
many pathogens. Lysozyme in tears, saliva, and mucous
secretions destroys the cell walls of susceptible bacteria The two main types of phagocytic cells in the mamma-
as they enter the openings around the eyes or the upper lian body are neutrophils and macrophages. Neutrophils,
respiratory tract. Pathogens in food or water and those in which circulate in the blood, are attracted by signals from
swallowed mucus must also contend with the acidic envi- infected tissues and then engulf and destroy the infecting
ronment of the stomach (pH 2), which kills most of them pathogens. Macrophages (“big eaters”), like the one shown
before they can enter the intestines. Similarly, secretions in Figure 43.1, are larger phagocytic cells. Some migrate
from oil and sweat glands give human skin a pH ranging throughout the body, whereas others reside permanently in
from 3 to 5, acidic enough to prevent the growth of organs and tissues where they are likely to encounter patho-
many bacteria. gens. For example, some macrophages are located in the
spleen, where pathogens in the blood are often trapped.
Cellular Innate Defenses
Two other types of cells—dendritic cells and eosinophils—
In mammals, as in insects, there are innate immune cells also have roles in innate defense. Dendritic cells mainly
dedicated to detecting, devouring, and destroying invading populate tissues, such as skin, that contact the environ-
pathogens. In doing so, these cells often rely on a Toll-like ment. They stimulate adaptive immunity against pathogens
receptor (TLR), a mammalian recognition protein similar that they encounter and engulf, as we’ll explore shortly.
to the Toll protein of insects. Upon recognizing pathogens, Eosinophils, often found in tissues underlying an epithelium,
TLR proteins produce signals that initiate responses tuned are important in defending against multicellular invaders,
to the invading microorganism. such as parasitic worms. Upon encountering such parasites,
eosinophils discharge destructive enzymes.
Each TLR protein binds to fragments of molecules char-
acteristic of a set of pathogens (Figure 43.5). For example,
TLR3, on the inner surface of vesicles formed by endocytosis,
binds to double-stranded RNA, a form of nucleic acid produced
by certain viruses. Similarly, TLR4, located on immune cell
plasma membranes, recognizes lipopolysaccharide, a type of
molecule found on the surface of many bacteria, and TLR5
recognizes flagellin, the main protein of bacterial flagella.

chapter 43  The Immune System 953

Cellular innate defenses in vertebrates also involve natural membrane integrity. Others, including the interferons and
killer cells. These cells circulate through the body and detect complement proteins, are unique to vertebrate immune
the abnormal array of surface proteins characteristic of some systems.
virus-infected and cancerous cells. Natural killer cells do not
engulf stricken cells. Instead, they release chemicals that lead Interferons are proteins that provide innate defense by
to cell death, inhibiting further spread of the virus or cancer. interfering with viral infections. Virus-infected body cells
secrete interferon proteins that induce nearby uninfected
Many cellular innate defenses in vertebrates involve cells to produce substances that inhibit viral replication.
the lymphatic system, a network that distributes the fluid In this way, these interferons limit the cell-to-cell spread of
called lymph throughout the body (Figure 43.6). Some viruses in the body, helping control viral infections such as
macrophages reside in lymph nodes, where they engulf colds and influenza. Some white blood cells secrete a different
pathogens that have entered the lymph from the interstitial type of interferon that helps activate macrophages, enhanc-
fluid. Dendritic cells reside outside the lymphatic system but ing their phagocytic ability. Pharmaceutical companies now
migrate to the lymph nodes after interacting with pathogens. use recombinant DNA technology to mass-produce interfer-
Within the lymph nodes, dendritic cells interact with other ons to help treat certain viral infections, such as hepatitis C.
immune cells, stimulating adaptive immunity.
The infection-fighting complement system consists of
Antimicrobial Peptides and Proteins roughly 30 proteins in blood plasma. These proteins circulate
in an inactive state and are activated by substances on the
In mammals, pathogen recognition triggers the production surface of many pathogens. Activation results in a cascade
and release of a variety of peptides and proteins that attack of biochemical reactions that can lead to lysis (bursting) of
pathogens or impede their reproduction. As in insects, some invading cells. The complement system also functions in the
of these defense molecules function as antimicrobial pep- inflammatory response, our next topic, as well as in the adap-
tides, damaging broad groups of pathogens by disrupting tive defenses discussed later in the chapter.

Figure 43.6  The human lymphatic system. The lymphatic system consists of lymphatic
vessels (shown in green), through which lymph travels, and structures that trap foreign substances.
These structures include lymph nodes (orange) and lymphoid organs (yellow): the adenoids, tonsils,
thymus, spleen, Peyer’s patches, and appendix. Steps 1–4 trace the flow of lymph and illustrate
the role of lymph nodes in activating adaptive immunity. (Concept 42.3 describes the relationship
between the lymphatic and circulatory systems.)

4 Lymphatic vessels Blood Interstitial 1 Interstitial fluid bathing
return lymph to the capillary fluid the tissues, along with the
blood via two large white blood cells in it,
ducts that drain into Adenoid Lymphatic continually enters lymphatic
Tonsils vessel vessels.
veins near the 2 Fluid inside the lymphatic
shoulders. Lymphatic system, called lymph, flows
vessels through lymphatic vessels
Thymus throughout the body.

Tissue 3 Within lymph nodes,
cells pathogens and foreign
particles in the circulating
Spleen Lymphatic lymph encounter and
vessel activate macrophages and
other cells that carry out
Peyer’s patches Lymph defensive actions.
(in small intestine) nodes

Appendix
(cecum)

Masses of
Lymph node defensive cells

954 unit seven  Animal Form and Function

Inflammatory Response stimulate the release of additional neutrophils from the bone
marrow. In the case of a severe infection, such as meningitis
When a splinter lodges under your skin, the surrounding or appendicitis, the number of white blood cells in the blood-
area becomes swollen and warm to the touch. Both changes stream may increase several-fold within only a few hours.
reflect a local inflammatory response, a set of events
triggered by signaling molecules released upon injury or A systemic inflammatory response sometimes involves
infection (Figure 43.7). Activated macrophages discharge fever. In response to certain pathogens, substances released
cytokines, signaling molecules that recruit neutrophils to the by activated macrophages cause the body’s thermostat to
site of injury or infection. In addition, mast cells, immune reset to a higher temperature (see Concept 40.3). There is
cells found in connective tissue, release the signaling mol- good evidence that fever can be beneficial in fighting cer-
ecule histamine at sites of damage. Histamine triggers tain infections, although the underlying mechanism is still
nearby blood vessels to dilate and become more permeable. a subject of debate. One hypothesis is that an elevated body
The resulting increase in local blood supply produces the red- temperature may enhance phagocytosis and, by speeding up
ness and increased skin temperature typical of the inflamma- chemical reactions, accelerate tissue repair.
tory response (from the Latin inflammare, to set on fire).
Certain bacterial infections can induce an overwhelming
During inflammation, cycles of signaling and response systemic inflammatory response, leading to a life-threatening
transform the site of injury and infection. Activated comple- condition known as septic shock. Characterized by very high
ment proteins promote further release of histamine, attracting fever, low blood pressure, and poor blood flow through capil-
more phagocytic cells (see Figure 43.7) that carry out addi- laries, septic shock occurs most often in the very old and the
tional phagocytosis. At the same time, enhanced blood flow very young. It is fatal in roughly one-third of cases and con-
to the site helps deliver antimicrobial peptides. The result is tributes to the death of more than 200,000 people each year
an accumulation of pus, a fluid rich in white blood cells, dead in the United States alone.
pathogens, and debris from damaged tissue.
Chronic (ongoing) inflammation can also threaten human
A minor injury or infection causes a local inflammatory health. For example, millions of individuals worldwide suffer
response, but more extensive tissue damage or infection may from Crohn’s disease and ulcerative colitis, often debilitating
lead to a response that is systemic (throughout the body). disorders in which an unregulated inflammatory response
Cells in injured or infected tissue often secrete molecules that disrupts intestinal function.

Figure 43.7  Major events in a local inflammatory response.

Pathogen Splinter

Signaling Macrophage
molecules
Mast cell Movement
of fluid

Capillary Phagocytosis

Red blood cells Neutrophil

1 At the injury site, mast cells release histamines, 2 Capillaries widen and become more permeable, 3 Neutrophils digest pathogens and
which cause nearby capillaries to dilate. allowing neutrophils and fluid containing cell debris at the site of injury, and
Macrophages release other signaling molecules antimicrobial peptides to enter the tissue. the tissue heals.
that attract neutrophils.

? From your experience with splinters, deduce whether the signals mediating Animation: Overview of the Inflammatory Response
an inflammatory response are short- or long-lived. Explain your answer.

chapter 43  The Immune System 955

Evasion of Innate Immunity by Pathogens B cell or T cell binds to an antigen, such as a bacterial or viral
protein, via a protein called an antigen receptor. Each anti-
Adaptations have evolved in some pathogens that enable gen receptor binds to just one part of one molecule from a par-
them to avoid destruction by phagocytic cells. For example, ticular pathogen, such as a species of bacteria or strain of virus.
the outer capsule that surrounds certain bacteria interferes
with molecular recognition and phagocytosis. One such The cells of the immune system produce millions of dif-
bacterium, Streptococcus pneumoniae, is a major cause of ferent antigen receptors. A given lymphocyte, however,
pneumonia and meningitis in humans (see Concept 16.1). produces just one variety; all of the antigen receptors made
by a single B or T cell are identical. Infection by a virus, bac-
Some bacteria are recognized but resist breakdown after terium, or other pathogen triggers activation of B and T cells
being engulfed by a host cell. One example is Mycobacterium with antigen receptors specific for parts of that pathogen.
tuberculosis, the bacterium shown in Figure 43.1. Rather than Although drawings of B and T cells typically include just a
being destroyed, this bacterium grows and reproduces within few antigen receptors, a single B or T cell actually has about
host cells, effectively hidden from the body’s immune defenses. 100,000 antigen receptors on its surface.
The result of this infection is tuberculosis (TB), a disease that
attacks the lungs and other tissues. Worldwide, TB kills more Antigens are usually large foreign molecules, either proteins
than 1 million people a year. or polysaccharides. Many antigens protrude from the surface of
foreign cells or viruses. Other antigens, such as toxins secreted
Concept Check 43.1 by bacteria, are released into the extracellular fluid.

1. Pus is both a sign of infection and an indicator of The small, accessible portion of an antigen that binds to
immune defenses in action. Explain. an antigen receptor is called an epitope. An example is a
group of amino acids in a particular protein. A single antigen
2. MAKE CONNECTIONS How do the molecules that usually has several epitopes, each binding a receptor with a
activate the vertebrate TLR signal transduction pathway different specificity. Because all antigen receptors produced
differ from the ligands in most other signaling pathways by a single B cell or T cell are identical, they bind to the same
(see Concept 11.2)? epitope. Each B or T cell thus displays specificity for a particu-
lar epitope, enabling it to respond to any pathogen that
3. WHAT IF? Parasitic wasps inject their eggs into host produces molecules containing that epitope.
larvae of other insects. If the host immune system doesn’t
kill the wasp egg, the egg hatches and the wasp larva The antigen receptors of B cells and T cells have similar
devours the host larva as food. Why can some insect components, but they encounter antigens in different ways.
species initiate an innate immune response to a wasp We’ll consider the two processes in turn.
egg, but others cannot?
For suggested answers, see Appendix A.

Concept  43.2 Antigen Recognition by B Cells and Antibodies

In adaptive immunity, receptors Each B cell antigen receptor is a Y-shaped protein consisting
provide pathogen-specific recognition of four polypeptide chains: two identical heavy chains and
two identical light chains. Disulfide bridges link the chains
together (Figure 43.9).

Vertebrates are unique in Figure 43.8  B and T Figure 43.9  The structure of a B cell antigen receptor.
having both adaptive and lymphocytes.
Antigen- Antigen-
innate immunity. The adap- Antigen binding binding site
tive response relies on T cells receptors site

and B cells, which are types VC Disulfide CV
V bridge V
of white blood cells called Variable
regions
lymphocytes (Figure 43.8).

Like all blood cells, lympho- B cell Constant
antigen regions
cytes originate from stem cells Mature B cell Mature T cell receptor Transmembrane
region
in the bone marrow. Some Light C C
chain
migrate from the bone marrow to the thymus, an organ in the

thoracic cavity above the heart (see Figure 43.6). These lym-

phocytes mature into T cells. Lymphocytes that remain and

mature in the bone marrow develop as B cells. (Lymphocytes

of a third type remain in the blood and become the natural Heavy Plasma
chain membrane
killer cells active in innate immunity.) Cytoplasm of B cell

Any substance that elicits a B or T cell response is called an B cell

antigen. In adaptive immunity, recognition occurs when a

956 unit seven  Animal Form and Function

Each light chain or heavy chain has a constant (C) region, structure as B cell antigen receptors but lack a membrane
where amino acid sequences vary little among the receptors anchor. As you’ll see later, antibodies provide a direct defense
on different B cells. The constant region of heavy chains con- against pathogens in body fluids.
tains a transmembrane region, which anchors the receptor
in the cell’s plasma membrane. As shown in Figure 43.9, each The antigen-binding site of a membrane-bound
light or heavy chain also has a variable (V) region, so named receptor or antibody has a unique shape that provides a
because its amino acid sequence varies extensively from one lock-and-key fit for a particular epitope. This stable inter-
B cell to another. Together, parts of a heavy-chain V region action involves any noncovalent bonds between an epit-
and a light-chain V region form an asymmetric binding site ope and the surface of the binding site. Differences in the
for an antigen. Therefore, each B cell antigen receptor has amino acid sequences of variable regions provide the
two identical antigen-binding sites. variation in binding surfaces that enables binding to be
highly specific.
Binding of a B cell antigen receptor to an antigen is an
early step in B cell activation, leading to formation of cells B cell antigen receptors and antibodies bind to intact anti-
that secrete a soluble form of the receptor (Figure 43.10a). gens in the blood and lymph. As illustrated in Figure 43.10b
This secreted protein is called an antibody, also known as an for antibodies, they can bind to antigens on the surface of
immunoglobulin (Ig). Antibodies have the same Y-shaped pathogens or free in body fluids.

Figure 43.10  Antigen recognition by B cells and antibodies. Antigen Recognition by T Cells

Antigen Antibody For a T cell, the antigen receptor consists of two different
receptor polypeptide chains, an a chain and a b chain, linked by a
disulfide bridge (Figure 43.11). Near the base of the T cell
B cell antigen receptor (often called simply a T cell receptor) is a
transmembrane region that anchors the molecule in the cell’s
Antigen Epitope plasma membrane. At the outer tip of the molecule, the vari-
able (V) regions of the α and β chains together form a single
Pathogen antigen-binding site. The remainder of the molecule is made
(a) B cell antigen receptors and antibodies. An antigen receptor up of the constant (C) regions.

of a B cell binds to an epitope, a particular part of an antigen. Whereas the antigen receptors of B cells bind to epitopes
Following binding, the B cell gives rise to cells that secrete a of intact antigens protruding from pathogens or circulating
soluble form of the antigen receptor. This soluble receptor, called free in body fluids, antigen receptors of T cells bind only
an antibody, is specific for the same epitope as the original B cell. to fragments of antigens that are displayed, or presented,
on the surface of host cells. The host protein that displays
the antigen fragment on the cell surface is called a major
histocompatibility complex (MHC) molecule. By dis-
playing antigen fragments, MHC molecules are essential for
antigen recognition by T cells.

Antibody A Antibody C Figure 43.11  The structure Antigen-
Antibody B of a T cell antigen receptor. binding
site
T cell VV
antigen CC Variable
receptor regions
Antigen Constant
Disulfide regions
(b) Antigen receptor specificity. Different antibodies can bridge Transmembrane
recognize distinct epitopes on the same antigen. Furthermore, region
antibodies can recognize free antigens as well as antigens on a
pathogen’s surface. T cell α chain β chain
Cytoplasm of T cell Plasma
MAKE CONNECTIONS The interactions depicted here involve a highly membrane
specific binding between antigen and receptor (see Figure 5.17). How is this
similar to an enzyme-substrate interaction (see Figure 8.15)?

chapter 43  The Immune System 957

The display and recognition of protein antigens begin right specificity, the antigen receptor on the T cell can bind
when a pathogen infects a cell of the animal host or parts of to both the antigen fragment and the MHC molecule. This
a pathogen are taken in by an immune cell (Figure 43.12a). interaction of an MHC molecule, an antigen fragment, and
Inside the animal cell, enzymes cleave each antigen into an antigen receptor triggers an adaptive immune response,
antigen fragments, which are smaller peptides. Each anti- as we’ll explore in Concept 43.3.
gen fragment binds to an MHC molecule, which transports
the bound peptide to the cell surface. The result is antigen B Cell and T Cell Development
presentation, the display of the antigen fragment in an
exposed groove of the MHC protein. Figure 43.12b shows a Now that you know how B cells and T cells recognize anti-
close-up view of antigen presentation, a process advertising gens, let’s consider four major characteristics of adaptive
the fact that a host cell contains a foreign substance. If the cell immunity. First, the immense repertoire of lymphocytes and
displaying an antigen fragment encounters a T cell with the receptors enables detection of antigens and pathogens never
before encountered. Second, adaptive immunity normally
Figure 43.12  Antigen recognition by T cells. has self-tolerance, the lack of reactivity against an animal’s
own molecules and cells. Third, cell proliferation triggered
Displayed T cell by activation greatly increases the number of B and T cells
antigen T cell antigen specific for an antigen. Fourth, there is a stronger and more
fragment receptor rapid response to an antigen encountered previously, due to a
MHC feature known as immunological memory, which we’ll explore
molecule later in the chapter.

Antigen Receptor diversity and self-tolerance arise as a lympho-
fragment cyte matures. Proliferation of cells and the formation of
immunological memory occur later, after a mature lym-
Pathogen phocyte encounters and binds to a specific antigen. We’ll
consider these four characteristics in the order in which
Host cell they develop.
(a) Antigen recognition by a T cell. Inside the host cell, an
Generation of B Cell and T Cell Diversity
antigen fragment from a pathogen binds to an MHC molecule
and is brought up to the cell surface, where it is displayed. The Each person makes more than 1 million different B cell anti-
combination of MHC molecule and antigen fragment is gen receptors and 10 million different T cell antigen recep-
recognized by a T cell. tors. Yet there are only about 20,000 protein-coding genes
in the human genome. How, then, do we generate so many
Top view different antigen receptors? The answer lies in combinations.
Antigen Think of selecting a cell phone that comes in three sizes and
fragment six colors. There are 18 (3 * 6) combinations to consider.
MHC Similarly, by combining variable elements, the immune
molecule system assembles millions of different receptors from a very
Host cell small collection of parts.

(b) A closer look at antigen presentation. As shown in this To understand the origin of receptor diversity, let’s con-
ribbon model, the top of the MHC molecule cradles an antigen sider an immunoglobulin (Ig) gene that encodes the light
fragment, like a bun holding a hot dog. An MHC molecule can chain of both membrane-bound B cell antigen receptors and
display many different antigen fragments, but the antigen secreted antibodies (immunoglobulins). Although we’ll ana-
receptor of a T cell is specific for a single antigen fragment. lyze only a single Ig light-chain gene, all B and T cell antigen
receptor genes undergo very similar transformations.

The capacity to generate diversity is built into the struc-
ture of Ig genes. A receptor light chain is encoded by three
gene segments: a variable (V) segment, a joining ( J ) seg-
ment, and a constant (C) segment. The V and J segments
together encode the variable region of the receptor chain,
while the C segment encodes the constant region. The
light-chain gene contains a single C segment, 40 differ-
ent V segments, and 5 different J segments. The alterna-
tive copies of the V and J segments are arrayed along the

958 unit seven  Animal Form and Function

Figure 43.13  Immunoglobulin (antibody) gene rearrangement. The joining of randomly
selected V and J gene segments (V39 and J5 in the example shown) results in a functional gene that
encodes the light-chain polypeptide of a B cell antigen receptor. Transcription, splicing, and translation
result in a light chain that combines with a polypeptide produced from an independently rearranged
heavy-chain gene to form a functional receptor. Mature B cells (and T cells) are exceptions to the
generalization that all nucleated cells in the body have exactly the same DNA.

DNA of V37 V38 V39 V40 J1 J2 J3 J4 J5 Intron C
undifferentiated
B cell

1 Recombination deletes DNA between
randomly selected V segment and J segment

DNA of V37 V38 V39 J5 Intron C
differentiated
B cell

Functional gene
2 Transcription of permanently

rearranged, functional gene

pre-mRNA V39 J5 Intron C

3 RNA processing (removal of intron;
addition of cap and poly-A tail)

mRNA Cap V39 J5 C Poly-A tail

4 Translation V V
V V

C C

Light-chain polypeptide V C Antigen receptor C C
B cell
Variable Constant
region region

MAKE CONNECTIONS Both alternative splicing and joining of V and J segments by recombination generate
diverse gene products from a limited set of gene segments (see Figure 18.13). How do these processes differ?

gene in a series (Figure 43.13). Because a functional gene The rearranged genes are transcribed, and the transcripts
is built from one copy of each type of segment, the pieces are processed for translation. Following translation, the
can be combined in 200 different ways (40 V * 5 J * 1 C). light chain and heavy chain assemble together, forming an
The number of different heavy-chain combinations is even antigen receptor (see Figure 43.13). Each pair of randomly
greater, resulting in even more diversity. rearranged heavy and light chains results in a different
antigen-binding site. For the total population of B cells in
Assembling a functional Ig gene requires rearranging the a human body, the number of such combinations has been
DNA. Early in B cell development, an enzyme complex called calculated as 3.5 * 106. Furthermore, mutations introduced
recombinase links one light-chain V gene segment to one J gene during VJ recombination add additional variation, making
segment. This recombination event eliminates the long stretch the number of antigen-binding specificities even greater.
of DNA between the segments, forming a single exon that is
part V and part J. Origin of Self-Tolerance

Recombinase acts randomly, linking any one of the 40 V In adaptive immunity, how does the body distinguish self
gene segments to any one of the 5 J gene segments. Heavy- from nonself? Because antigen receptor genes are randomly
chain genes undergo a similar rearrangement. In any given rearranged, some immature lymphocytes produce receptors
cell, however, only one allele of a light-chain gene and one specific for epitopes on the organism’s own molecules. If these
allele of a heavy-chain gene are rearranged. Furthermore, self-reactive lymphocytes were not eliminated or inactivated,
the rearrangements are permanent and are passed on to the the immune system could not distinguish self from nonself
daughter cells when the lymphocyte divides. and would attack body proteins, cells, and tissues. Instead,
as lymphocytes mature in the bone marrow or thymus, their
After both a light-chain and a heavy-chain gene have
been rearranged, antigen receptors can be synthesized.

chapter 43  The Immune System 959

antigen receptors are tested for self-reactivity. Some B and For T cells, the effector forms are helper T cells and cytotoxic
T cells with receptors specific for the body’s own molecules T cells, whose roles we’ll explore in Concept 43.3. The remain-
are destroyed by apoptosis, which is a programmed cell death ing cells in the clone become memory cells, long-lived cells
(see Concept 11.5). The remaining self-reactive lymphocytes that can give rise to effector cells if the same antigen is encoun-
are typically rendered nonfunctional, leaving only those that tered later in the animal’s life.
react to foreign molecules. Since the body normally lacks
mature lymphocytes that can react against its own compo- The proliferation of a B cell or T cell into a clone of cells
nents, the immune system is said to exhibit self-tolerance. occurs in response to a specific antigen and to immune cell
signals. The process is called clonal selection because an
Proliferation of B Cells and T Cells encounter with an antigen selects which lymphocyte will
divide to produce a clonal population of thousands of cells
Despite the enormous variety of antigen receptors, only a tiny specific for a particular epitope. Cells that have antigen
fraction are specific for a given epitope. How then does an receptors specific for other antigens do not respond.
effective adaptive response develop? To begin with, an antigen
is presented to a steady stream of lymphocytes in the lymph Figure 43.14 summarizes the process of clonal selection,
nodes (see Figure 43.6) until a match is made. A successful using the example of B cells, which generate memory cells
match between an antigen receptor and an epitope initiates and plasma cells. When T cells undergo clonal selection, they
events that activate the lymphocyte bearing the receptor. generate memory T cells and effector T cells (cytotoxic T cells
and helper T cells).
Once activated, a B cell or T cell undergoes multiple cell
divisions. For each activated cell, the result of this proliferation Immunological Memory
is a clone, a population of cells that are identical to the original
cell. Some cells from this clone become effector cells, mostly Immunological memory is responsible for the long-term
short-lived cells that take effect immediately against the anti- protection that a prior infection provides against many dis-
gen and any pathogens producing that antigen. For B cells, eases, such as chicken pox. This type of protection was noted
the effector forms are plasma cells, which secrete antibodies. almost 2,400 years ago by the Greek historian Thucydides. He
observed that individuals who had recovered from the plague

Figure 43.14  Clonal selection of B cells. B cells that differ
in antigen specificity

Antigen Antigen
receptor

1 Antigens bind to
the antigen receptors

of only one of the
three B cells shown.
2 The selected B cell
proliferates, forming
a clone of identical

cells bearing
receptors for the

antigen.

3 Some daughter cells Antibody 3 (continued) … and
develop into Plasma cells other daughter cells
develop into short-lived
long-lived memory plasma cells that secrete
cells that can respond antibodies specific
for the antigen.
rapidly upon Animation: Clonal Selection
subsequent exposure
to the same antigen …

Memory cells

VISUAL SKILLS For the purpose of illustration, this figure shows only a few of each
type of cell or molecule. Based on what you have read in Concept 43.2, provide estimates

of the number of different B cells and number of antigen receptors on each B cell.

960 unit seven  Animal Form and Function

could safely care for those who were sick or dying, “for the and T cells, these two classes of lymphocytes fight infection
same man was never attacked twice—never at least fatally.” in different ways and in different settings, as we’ll explore in
Concept 43.3.
Prior exposure to an antigen alters the speed, strength, and
duration of the immune response. The effector cells formed Concept Check 43.2
by clones of lymphocytes after an initial exposure to an anti-
gen produce a primary immune response. The primary 1. DRAW IT Sketch a B cell antigen receptor. Label the V
response peaks about 10–17 days after the initial exposure. and C regions of the light and heavy chains. Label the
If the same antigen is encountered again later, there is a antigen-binding sites, disulfide bridges, and transmem-
secondary immune response, a response that is faster brane region. Where are these features located relative
(typically peaking only 2–7 days after exposure), of greater to the V and C regions?
magnitude, and more prolonged. These differences between
primary and secondary immune responses are readily appar- 2. Explain two advantages of having memory cells when a
ent in a graph of the concentrations of specific antibodies in pathogen is encountered for a second time.
blood over time (Figure 43.15).
3. WHAT IF? If both copies of a light-chain gene and
The secondary immune response relies on the reservoir a heavy-chain gene recombined in each (diploid)
of T and B memory cells generated upon initial exposure to B cell, how would this affect B cell development
an antigen. Because these cells are long-lived, they provide and function?
the basis for immunological memory, which can span many
decades. (Most effector cells have much shorter life spans.) For suggested answers, see Appendix A.
If an antigen is encountered again, memory cells specific for
that antigen enable the rapid formation of clones of thou- Concept  43.3
sands of effector cells also specific for that antigen, thus
generating a greatly enhanced immune defense. Adaptive immunity defends
against infection of body fluids
Although the processes for antigen recognition, clonal and body cells
selection, and immunological memory are similar for B cells
Having considered how clones of lymphocytes arise, we now
Figure 43.15  The specificity of immunological memory. explore how these cells help fight infections and minimize
Long-lived memory cells that are generated in the primary response to damage by pathogens. The defenses provided by B and T
antigen A give rise to a heightened secondary response to the same lymphocytes can be divided into humoral and cell-mediated
antigen but don’t affect the primary response to another antigen (B). immune responses. The humoral immune response
occurs in the blood and lymph (once called body humors, or
Primary immune response Secondary immune response fluids). In this response, antibodies help neutralize or eliminate
to antigen A produces to antigen A produces antibodies to A; toxins and pathogens in body fluids. In the cell-mediated
antibodies to A. primary immune response to antigen immune response, specialized T cells destroy infected host
B produces antibodies to B. cells. Both humoral and cellular immunity can include a pri-
mary immune response and a secondary immune response,
104 with memory cells enabling the secondary response.

Antibody concentration 103 Helper T Cells: Activating Adaptive Immunity
(arbitrary units)
Antibodies A type of T cell called a helper T cell activates humoral
to A and cell-mediated immune responses. Before this can hap-
102 Antibodies pen, however, two conditions must be met. First, a foreign
to B molecule must be present that can bind specifically to the
antigen receptor of the helper T cell. Second, this antigen
101 must be displayed on the surface of an antigen-presenting
cell. An antigen-presenting cell can be a dendritic cell,
100 7 14 21 28 35 42 49 56 macrophage, or B cell.
0
Like immune cells, infected cells can display antigens on
Exposure Exposure to their surface. What then distinguishes an antigen-presenting
to antigen A antigens A and B cell? The answer lies in the existence of two classes of MHC
Time (days) molecules. Most body cells have only the class I MHC mol-
ecules, but antigen-presenting cells have class I and class II
INTERPRET THE DATA Assume that on average one out of every 105 MHC molecules. Class II molecules provide a molecular sig-
B cells in the body is specific for antigen A on day 16 and that the number nature by which an antigen-presenting cell is recognized.

of B cells producing a specific antibody is proportional to the concentration

of that antibody. What would you predict is the frequency of B cells specific

for antigen A on day 36?

chapter 43  The Immune System 961

Figure 43.16  The central role of helper T cells in humoral and cell-mediated BioFlix® Animation: Activation of a Helper T Cell by
immune responses. Here, a helper T cell responds to a dendritic cell displaying an antigen. a Dendritic Cell (Example: Infection by a Rhinovirus)

Antigen- Antigen Clone of activated helper T cells
presenting fragment
cell

Pathogen

Antigen Class II MHC + + +
receptor molecule Cytokines B cell Cytotoxic
Accessory HUMORAL
protein (CD4) IMMUNITY T cell
(secretion of CELL-MEDIATED
+ antibodies
by plasma cells) IMMUNITY
Helper T cell (attack on
infected

cells)

1 An antigen-presenting cell engulfs a 2 Binding of the helper T cell promotes 3 Cell proliferation produces a clone of
pathogen, degrades it, and displays secretion of cytokines by the antigen- activated helper T cells. All cells in the clone
antigen fragments complexed with class II presenting cell. These cytokines, along with have receptors for the same antigen
MHC molecules on the cell surface. A cytokines from the helper T cell itself, fragment complex with the same antigen
specific helper T cell binds to this complex activate the helper T cell and stimulate its specificity. These cells secrete other
via its antigen receptor and an accessory proliferation. cytokines, which help activate B cells and
protein called CD4. cytotoxic T cells.

A helper T cell and the antigen-presenting cell displaying Stimulated by both an antigen and cytokines, the B cell pro-
its specific epitope have a complex interaction (Figure 43.16).
The antigen receptors on the surface of the helper T cell bind liferates and differentiates into memory B cells and antibody-
to the antigen fragment and to the class II MHC molecule
displaying that fragment on the antigen-presenting cell. At secreting plasma cells.
the same time, an accessory protein called CD4 on the helper
T cell surface binds to the class II MHC molecule, helping The pathway for antigen processing and display in B cells dif-
keep the cells joined. As the two cells interact, signals in the
form of cytokines are exchanged. For example, the cytokines fers from that in other antigen-presenting cells. A macrophage
secreted from a dendritic cell act in combination with the
antigen to stimulate the helper T cell, causing it to produce its or dendritic cell can present fragments from a wide variety of
own set of cytokines. Also, extensive contact between the cell
surfaces enables further information exchange. protein antigens, whereas a B cell presents only the antigen

Antigen-presenting cells interact with helper T cells in sev- to which it specifically binds. When an antigen first binds to
eral contexts. Antigen presentation by a dendritic cell or mac-
rophage activates a helper T cell, which proliferates, forming receptors on the surface of a B cell, the cell takes in a few foreign
a clone of activated cells. In contrast, B cells present antigens
to already activated helper T cells, which in turn activate the molecules by receptor-mediated endocytosis (see Figure 7.19).
B cells themselves. Activated helper T cells also help stimulate
cytotoxic T cells, as you’ll see shortly. The class II MHC protein of the B cell then presents an antigen

B Cells and Antibodies: fragment to a helper T cell. This direct cell-to-cell contact is
A Response to Extracellular Pathogens
usually critical to B cell activation (see step 2 in Figure 43.17).
Secretion of antibodies is the hallmark of the humoral
immune response. It begins with activation of the B cells. B cell activation leads to a robust humoral immune

Activation of B Cells response: A single activated B cell gives rise to thousands of

As illustrated in Figure 43.17, activation of B cells involves identical plasma cells. These plasma cells stop expressing a
both helper T cells and proteins on the surface of pathogens.
membrane-bound antigen receptor and begin producing and
962 unit seven  Animal Form and Function
secreting antibodies (see step 3 in Figure 43.17). Each plasma

cell secretes approximately 2,000 antibodies every second

during its four- to five-day life span, nearly a trillion antibody

molecules in total. Furthermore, most antigens recognized by

B cells contain multiple epitopes. Plasma
An exposure to a single antigen cell

therefore normally activates a

variety of B cells, which give rise

to different plasma cells produc-

ing antibodies directed against

different epitopes on the com-

mon antigen. 2 μm

Figure 43.17  Activation of a B cell in the humoral immune response. Most protein antigens
require activated helper T cells to trigger a humoral response. A macrophage (shown here) or a dendritic cell
can activate a helper T cell, which in turn can activate a B cell to give rise to antibody-secreting plasma cells.

Antigen-presenting cell Pathogen

Antigen B cell
fragment

Class II MHC Memory B cells
molecule
Antigen Accessory protein +
receptor (CD4) Cytokines

Helper T cell Activated Plasma cells Secreted antibodies
helper T cell

1 After an antigen-presenting cell engulfs and 2 When a B cell with receptors for the same 3 The activated B cell proliferates and
degrades a pathogen, it displays an antigen epitope internalizes the antigen, it displays differentiates into memory B cells and
fragment complexed with a class II MHC an antigen fragment on the cell surface in a antibody-secreting plasma cells. The
molecule. A helper T cell that recognizes complex with a class II MHC molecule. An secreted antibodies are specific for the
the complex is activated with the aid of activated helper T cell bearing receptors same antigen that initiated the response.
cytokines secreted from the antigen- specific for the displayed fragment binds to
presenting cell. and activates the B cell. BioFlix® Animation: Adaptive Defenses: B Cells
(Example: Infection by a Rhinovirus)
? Laonotikgienng at the steps in this figure, propose a function for the cell-surface
receptors of memory B cells.

Antibody Function thereby promoting phagocytosis (Figure 43.19). Because
each antibody has two antigen-binding sites, antibodies can
Antibodies do not directly kill pathogens, but by binding to also facilitate phagocytosis by linking bacterial cells, viruses,
antigens, they interfere with pathogen activity or mark patho- or other foreign substances into aggregates.
gens in various ways for inactivation or destruction. Consider,
for example, neutralization, a process in which antibodies When antibodies facilitate phagocytosis, as in opsoniza-
bind to proteins on the surface of a virus (Figure 43.18). tion, they also help fine-tune the humoral immune response.
The bound antibodies prevent infection of a host cell, thus Recall that phagocytosis enables macrophages and dendritic
neutralizing the virus. Similarly, antibodies sometimes bind cells to present antigens to and stimulate helper T cells, which
to toxins released in body fluids, preventing the toxins from in turn stimulate the very B cells whose antibodies contribute
entering body cells. to phagocytosis. This positive feedback between innate and
adaptive immunity contributes to a coordinated, effective
In opsonization, antibodies that are bound to antigens on response to infection.
bacteria do not block infection, but instead present a read-
ily recognized structure for macrophages or neutrophils, Figure 43.19  Opsonization

Figure 43.18  Neutralization

Antibody

Antibodies bound to Bacterium
antigens on the surface
Virus of a virus neutralize it by
blocking its ability to
bind to a host cell.

Macrophage

Binding of antibodies to antigens on the
surface of bacteria promotes phagocytosis
by macrophages and neutrophils.

chapter 43  The Immune System 963

Figure 43.20  Activation of complement system complement protein activity results in the lysis of foreign
and pore formation. cells and produces factors that promote inflammation or
stimulate phagocytosis.
Complement proteins
Formation of Although antibodies are the cornerstones of the response
membrane in body fluids, there is also a mechanism by which they can
attack complex bring about the death of infected body cells. When a virus
uses a cell’s biosynthetic machinery to produce viral pro-
Flow of water teins, these viral products can appear on the cell surface. If
and ions antibodies specific for epitopes on these viral proteins bind
to the exposed proteins, the presence of bound antibody at
Pore the cell surface can recruit a natural killer cell. The natural
killer cell then releases proteins that cause the infected cell
Foreign Antigen to undergo apoptosis. Thus the activities of the innate and
cell adaptive immune systems are once again closely linked.

Binding of antibodies to After activation of the complement B cells can express five types, or classes, of immunoglobu-
antigens on the surface system, the membrane attack lin (IgA, IgD, IgE, IgG, and IgM). For a given B cell, each class
of a foreign cell activates complex forms pores in the cell’s has an identical antigen-binding specificity but a distinct
the complement system. membrane, allowing water and ions heavy-chain C region. The B cell antigen receptor, known as
to rush in. The cell swells and lyses. IgD, is exclusively membrane bound. The other four classes
have soluble forms, such as the antibodies found in blood,
Antibodies sometimes work together with the proteins of tears, saliva, and breast milk.
the complement system (Figure 43.20). (The name complement
reflects the fact that these proteins add to the effectiveness of Cytotoxic T Cells:
antibody-directed attacks on bacteria.) Binding of a comple- A Response to Infected Host Cells
ment protein to an antigen-antibody complex on a foreign
cell triggers the generation of a membrane attack complex that In the absence of an immune response, pathogens can
forms a pore in the membrane of the cell. Ions and water reproduce in and kill infected cells (Figure 43.21). In the
rush into the cell, causing it to swell and lyse. Whether acti- cell-mediated immune response, cytotoxic T cells use toxic
vated as part of innate or adaptive defenses, this cascade of proteins to kill cells infected by viruses or other intracellular
pathogens before pathogens fully mature. To become active,
cytotoxic T cells require signals from helper T cells and inter-
action with an antigen-presenting cell. Fragments of foreign

Figure 43.21  The killing action of cytotoxic T cells on an infected host cell. BioFlix® Animation: Adaptive Defenses: Cytotoxic
An activated cytotoxic T cell releases molecules that make pores in an infected cell’s T Cells (Example: Infection by a Rhinovirus)
membrane and enzymes that break down proteins, promoting the cell’s death.
Released
Cytotoxic T cell cytotoxic T cell

Accessory Antigen Perforin Dying infected cell
protein (CD8) receptor Pore
Class I MHC Granzymes
molecule

Infected Antigen
cell fragment

1 An activated cytotoxic T cell binds to a 2 The T cell releases perforin molecules, 3 The granzymes initiate apoptosis within the
class I MHC–antigen fragment complex on which form pores in the infected cell infected cell, leading to fragmentation of
an infected cell via its antigen receptor and membrane, and granzymes, enzymes that the nucleus and cytoplasm and eventual cell
an accessory protein called CD8. break down proteins. Granzymes enter the death. The released cytotoxic T cell can
infected cell by endocytosis. attack other infected cells.

964 unit seven  Animal Form and Function

proteins produced in infected host cells associate with class I Summary of the Humoral and Cell-Mediated
MHC molecules and are displayed on the cell surface, where Immune Responses
they can be recognized by cytotoxic T cells. As with helper
T cells, cytotoxic T cells have an accessory protein that binds As noted earlier, both humoral and cell-mediated immu-
to the MHC molecule. This accessory protein, called CD8, nity can include primary and secondary immune responses.
helps keep the two cells in contact while the cytotoxic T cell Memory cells of each type—helper T cell, B cell, and cytotoxic
is activated. T cell—enable the secondary response. For example, when
body fluids are reinfected by a pathogen encountered previ-
The targeted destruction of an infected host cell by a cyto- ously, memory B cells and memory helper T cells initiate a
toxic T cell involves the secretion of proteins that disrupt secondary humoral response. Figure 43.22 summarizes adap-
membrane integrity and trigger cell death (apoptosis; see tive immunity, reviews the events that initiate humoral and
Figure 43.21). The death of the infected cell not only deprives cell-mediated immune responses, highlights the difference in
the pathogen of a place to multiply but also exposes cell con- response to pathogens in body fluids versus in body cells, and
tents to circulating antibodies, which mark released antigens emphasizes the central role of the helper T cell.
for disposal.

Figure 43.22  An overview of the adaptive immune response.

HUMORAL IMMUNE RESPONSE CELL-MEDIATED IMMUNE RESPONSE

Antigen (1st exposure) Key
Taken in by + Stimulates
Gives rise to

Antigen-
presenting cell
+ +

+

B cell + Helper T cell + Cytotoxic T cell

Memory
helper T cells

+++

Antigen (2nd exposure)

Plasma cells + Memory Active
Memory B cells cytotoxic T cells cytotoxic T cells

Secreted
antibodies

Defend against extracellular pathogens in blood and lymph by Defend against intracellular pathogens
binding to antigens, thereby neutralizing pathogens or making them and certain cancers by binding to and
better targets for phagocytic cells and complement proteins. lysing the infected cells.

VISUAL SKILLS Identify each arrow as representing part of the BioFlix® Animation: Summary of the Adaptive Immune Response
primary response or secondary response. (Example: Infection by a Rhinovirus)

chapter 43  The Immune System 965

Immunization Active and Passive Immunity

The protection provided by a second immune response The discussion of adaptive immunity has to this point

provides the basis for immunization, the use of antigens focused on active immunity, the defenses that arise

artificially introduced into the body to generate an adap- when a pathogen infection or immunization prompts an

tive immune response and memory cell formation. In 1796, immune response. A different type of immunity results

Edward Jenner noted that milkmaids who had cowpox, a when the IgG antibodies in the blood of a pregnant female

mild disease usually seen only in cows, did not contract cross the placenta to her fetus. This protection is called

smallpox, a far more dangerous disease. In the first docu- passive immunity because the antibodies in the recipient

mented immunization (or vaccination, from the Latin vacca, (in this case, the fetus) are produced by another individual

cow), Jenner used the cowpox virus to induce adaptive (the mother). IgA antibodies present in breast milk provide

immunity against the closely related smallpox virus. Today, additional passive immunity to the infant’s digestive tract

immunizations are carried out with vaccines—preparations while the infant’s immune system develops. Because pas-

of antigen—obtained from many sources, including inacti- sive immunity does not involve the recipient’s B and T

vated bacterial toxins, killed or weakened pathogens, and cells, it persists only as long as the transferred antibodies

even genes encoding microbial proteins. Because all of these last (a few weeks to a few months).

agents induce a primary immune response and immunologi- In artificial passive immunization, antibodies from an

cal memory, an encounter with the pathogen from which immune animal are injected into a nonimmune animal.

the vaccine was derived triggers a rapid and strong second- For example, humans bitten by venomous snakes are some-

ary immune response (see Figure 43.15). times treated with antivenin, serum from sheep or horses

Vaccination programs have been successful against many that have been immunized against a snake venom. When

infectious diseases that once killed or incapacitated large injected immediately after a snakebite, the antibodies in

numbers of people. A worldwide vaccination campaign led antivenin can neutralize toxins in the venom before the

to eradication of smallpox in the late 1970s. In industrial- toxins do massive damage.

ized nations, routine immunization of

infants and children has dramatically Figure 43.23  Vaccine-based protection against two life-threatening communicable
reduced the incidence of sometimes diseases. The graphs show deaths by year in the United States caused by polio and measles.
devastating diseases, such as polio and The maps show examples of the global progress against these two diseases.
measles (Figure 43.23). Unfortunately,
not all pathogens are easily managed Annual deaths from polio in U.S. 3,500 Vaccine 1988 2014
by vaccination. Furthermore, some vac- 3,000 introduced

cines are not readily available in impov- 2,500
erished areas of the globe. 2,000

Misinformation about vaccine safety

and disease risk has led to a grow- 1,500

ing public health problem. Consider 1,000 Countries that have eliminated polio
measles as just one example. Side effects 500
of immunization are remarkably rare,

with fewer than one in a million chil- 01950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 2015
dren suffering a significant allergic Year
reaction to the measles vaccine. The

disease remains quite dangerous to Annual deaths from measles in U.S. 700 Vaccine Rates of measles vaccination for infants in 2014
this day, however, killing more than 600 introduced 90–100%
200,000 people worldwide each year. 500 80–89%
Declines in vaccination rates in parts 400 50–79%
of the United Kingdom, Russia, and the 300 <50%
United States have resulted in a number Data not
of recent measles outbreaks and many available

preventable deaths. In 2014–2015, a 200

measles outbreak triggered by a visi- 100
tor to a Disney theme park in Southern 01950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 2015
California spread to multiple states

and affected people ranging in age Year

from 6 weeks to 70 years.

966 unit seven  Animal Form and Function

Antibodies as Tools can stimulate an immune response in the recipient of a graft
or transplant, causing rejection. To minimize rejection of a
Antibodies that an animal produces after exposure to an anti- transplant or graft, surgeons use donor tissue bearing MHC
gen are the products of many different clones of plasma cells, molecules that match those of the recipient as closely as pos-
each specific for a different epitope. However, antibodies can sible. In addition, the recipient takes medicines that suppress
also be prepared from a single clone of B cells grown in culture. immune responses (but as a result leave the recipient more
The monoclonal antibodies produced by such a culture are susceptible to infections).
identical and specific for the same epitope on an antigen.

Monoclonal antibodies have provided

the basis for many recent advances in Figure 43.24  A comprehensive test for past viral encounters. By combining the
medical diagnosis and treatment. For power of DNA sequencing with the specificity of antigen recognition by antibodies, researchers
example, home pregnancy test kits use can identify every virus that an immune system has encountered during the person’s lifetime.

monoclonal antibodies to detect human

chorionic gonadotropin (hCG). Because

hCG is produced as soon as an embryo

implants in the uterus (see Concept 46.5),

the presence of this hormone in a wom- Bacteriophage 1 Viruses that infect humans
an’s urine is a reliable indicator for a very Peptide have unique peptides on
early stage of pregnancy. Monoclonal their surface (insets). By
antibodies are injected as a therapy for introducing short DNA
a number of human diseases, including sequences from all known
certain cancers. human viruses into copies of
a bacteriophage genome,
One of the most recently developed researchers generated a
antibody tools uses a single drop of blood collection of 100,000
to identify every virus that a person has bacteriophages, each
encountered through infection or vac- displaying many copies of
one viral peptide.

cination. To detect the antibodies formed

against these viruses, researchers generate Drop of blood
a set of nearly 100,000 bacteriophages,
each of which displays a different peptide Mixture of 2 The bacteriophages are
from one of the roughly 200 species of bacteriophages combined with serum from a
viruses that infect humans. Figure 43.24 and antibodies drop of a person’s blood. The
provides an overview of how this serum contains antibodies,
technique works. Unbound some of which were
antibodies produced in response to
Immune Rejection exposure to viruses. Any
antibody that is specific for a
Like pathogens, cells from another viral peptide binds to a
person can be recognized as foreign bacteriophage displaying
and attacked by immune defenses. For that peptide. Bacteriophages
example, skin transplanted from one displaying peptides from
viruses never encountered
are not recognized.

person to a genetically nonidentical Antibodies
person will look healthy for a week or bound to
so but will then be destroyed (rejected) viral peptides

by the recipient’s immune response.

It turns out that MHC molecules are a DNA sequencing
primary cause of rejection. Why? Each

of us expresses MHC proteins from more

than a dozen different MHC genes. 3 DNA sequencing of
Furthermore, there are more than 100 bacteriophages to which
different versions, or alleles, of human Virus antibodies are bound
MHC genes. As a consequence, the sets Prior identifies the complete set
of MHC proteins on cell surfaces are exposure? of viruses to which a person
Yes No Yes has been exposed.

likely to differ between any two people, WHAT IF? All of the antibodies are shown with just one antigen binding site occupied. If a single antibody
except identical twins. Such differences bound to two bacteriophages, how would this affect the results?

chapter 43  The Immune System 967

Blood Groups we’ll first examine the disorders and diseases that arise
when adaptive immunity is blocked or misregulated. We’ll
In the case of blood transfusions, the recipient’s immune sys- then turn to some of the evolutionary adaptations of patho-
tem can recognize carbohydrates on the surface of blood cells gens that diminish the effectiveness of adaptive immune
as foreign, triggering an immediate and devastating reaction. responses in the host.
To avoid this danger, the so-called ABO blood groups of the
donor and recipient must be taken into account. Red blood Exaggerated, Self-Directed, and Diminished
cells are designated as type A if they have the A carbohydrate Immune Responses
on their surface. Similarly, the B carbohydrate is found on the
surface of type B red blood cells; both A and B carbohydrates The highly regulated interplay among lymphocytes, other
are found on type AB red blood cells; and neither carbohy- body cells, and foreign substances generates an immune
drate is found on type O red blood cells (see Figure 14.11). response that provides extraordinary protection against
many pathogens. When allergic, autoimmune, or immuno-
Why does the immune system recognize particular sugars deficiency disorders disrupt this delicate balance, the effects
on red blood cells? It turns out that we are frequently exposed are frequently severe.
to certain bacteria that have epitopes very similar to the car-
bohydrates on blood cells. A person with type A blood will Allergies
respond to the bacterial epitope similar to the B carbohydrate
and make antibodies that will react with any B carbohydrate Allergies are exaggerated (hypersensitive) responses to cer-
encountered upon a transfusion. However, that same person tain antigens called allergens. The most common allergies
doesn’t make antibodies against the bacterial epitope similar involve antibodies of the IgE class. Hay fever, for instance,
to the A carbohydrate because lymphocytes that would be occurs when plasma cells secrete IgE antibodies specific
reactive with the body’s own cells and molecules were for antigens on the surface of pollen grains (Figure 43.25).
inactivated or eliminated during development. Some IgE antibodies attach by their base to mast cells in
connective tissues. Pollen grains that enter the body later
To understand how ABO blood groups affect transfusions, attach to the antigen-binding sites of these IgE antibodies.
let’s consider further the example of a person with type A
blood receiving a transfusion of type B blood. The person’s Figure 43.25  Mast cells, IgE, and
anti-B antibodies would cause the transfused red blood cells the allergic response. In this example,
to undergo lysis, triggering chills, fever, shock, and perhaps IgE pollen grains act as the allergen.
kidney malfunction. At the same time, anti-A antibodies in
the donated type B blood would act against the recipient’s red Mast Allergen
blood cells. Applying the same logic to a type O person, we cell (second
can see that such interactions would cause a problem upon 1 IgE antibodies exposure)
transfusion of any other blood type. Fortunately, the discov- produced in response
ery of enzymes that can cleave the A and B carbohydrates to initial exposure
from red blood cells may eliminate this problem in the future. to an allergen bind to
receptors on mast cells.
Concept Check 43.3
2 On subsequent exposure Vesicle
1. If a child were born without a thymus gland, what cells to the same allergen, IgE Histamine
and functions of the immune system would be deficient? molecules attached to a
Explain. mast cell recognize and
bind the allergen.
2. Treatment of antibodies with a particular protease clips the
heavy chains in half, releasing the two arms of the Y-shaped 3 Cross-linking of adjacent IgE
molecule. How might the antibodies continue to function? molecules triggers release of
histamine and other chemicals,
3. WHAT IF? Suppose that a snake handler bitten by a leading to allergy symptoms.
particular venomous snake species was treated with
antivenin. Why might the same treatment for a second
such bite have a harmful side effect?

For suggested answers, see Appendix A.

Concept  43.4

Disruptions in immune system function
can elicit or exacerbate disease

Although adaptive immunity offers significant protection
against a wide range of pathogens, it is not fail-safe. Here

968 unit seven  Animal Form and Function

Such attachment cross-links adjacent IgE molecules, induc- Figure 43.26  X-ray of hands that are deformed
ing the mast cell to release histamine and other inflam- by rheumatoid arthritis.
matory chemicals. Acting on a variety of cell types, these
chemicals bring about the typical allergy symptoms: immune system function and significantly reduces sus-
sneezing, runny nose, teary eyes, and smooth muscle con- ceptibility to the common cold and other infections of the
tractions in the lungs that can inhibit effective breathing. upper respiratory tract. In contrast, exercise to the point
Drugs known as antihistamines block receptors for hista- of exhaustion leads to more frequent infections and more
mine, diminishing allergy symptoms (and inflammation). severe symptoms. Studies of marathon runners support the
conclusion that exercise intensity is the critical variable.
An acute allergic response sometimes leads to a life- On average, such runners get sick less often than their more
threatening reaction called anaphylactic shock. Inflammatory sedentary peers during training, a time of moderate exer-
chemicals released from immune cells trigger constriction of tion, but markedly more often in the period immediately
bronchioles and sudden dilation of peripheral blood vessels, following the grueling race itself. Similarly, psychological
which causes a precipitous drop in blood pressure. Death may stress has been shown to disrupt immune system regulation
occur within minutes due to the inability to breathe and lack by altering the interplay of the hormonal, nervous, and
of blood flow. Substances that can cause anaphylactic shock immune systems (see Figure 45.20). Research also confirms
in allergic individuals include bee venom, penicillin, peanuts, that rest is important for immunity: Adults who averaged
and shellfish. People with severe hypersensitivities often fewer than 7 hours of sleep got sick three times as often
carry an autoinjector containing the hormone epinephrine. when exposed to a cold virus as those who averaged
An injection of epinephrine rapidly counteracts this allergic at least 8 hours.
response, constricting peripheral blood vessels, reducing
swelling in the throat, and relaxing muscles in the lungs Immunodeficiency Diseases
to help breathing (see Figure 45.20b).
A disorder in which an immune system response to anti-
Autoimmune Diseases gens is defective or absent is called an immunodeficiency.
Whatever its cause and nature, an immunodeficiency can
In some people, the immune system is active against par- lead to frequent and recurrent infections and increased
ticular molecules of the body, causing an autoimmune susceptibility to certain cancers.
disease. Such a loss of self-tolerance has many forms. In
systemic lupus erythematosus, commonly called lupus, the An inborn immunodeficiency results from a genetic or
immune system generates antibodies against histones and developmental defect in the production of immune system
DNA released by the normal breakdown of body cells. These cells or of specific proteins, such as antibodies or the pro-
self-reactive antibodies cause skin rashes, fever, arthritis, teins of the complement system. Depending on the specific
and kidney dysfunction. Other targets of autoimmunity defect, either innate or adaptive defenses—or both—may be
include the insulin-producing beta cells of the pancreas impaired. In severe combined immunodeficiency (SCID),
(in type 1 diabetes) and the myelin sheaths that encase functional lymphocytes are rare or absent. Lacking an adap-
many neurons (in multiple sclerosis). tive immune response, SCID patients are susceptible to infec-
tions that can cause death in infancy, such as pneumonia and
Heredity, gender, and environment all influence suscep- meningitis. Treatments include bone marrow and stem cell
tibility to autoimmune disorders. For example, members of transplantation.
certain families show an increased susceptibility to particular
autoimmune disorders. In addition, many autoimmune dis-
eases afflict females more often than males. Women are nine
times as likely as men to suffer from lupus and two to three
times as likely to develop rheumatoid arthritis, a damaging
and painful inflammation of the cartilage and bone in joints
(Figure 43.26). The causes of this sex bias, as well as the rise
in autoimmune disease frequency in industrialized countries,
are areas of active research and debate.

An additional focus of current research on autoimmune
disorders is the activity of regulatory T cells, nicknamed Tregs.
These specialized T cells help modulate immune system activ-
ity and prevent response to self-antigens.

Exertion, Stress, and the Immune System

Many forms of exertion and stress influence immune
system function. For example, moderate exercise improves

chapter 43  The Immune System 969

Later in life, exposure to chemicals or biological agents Latency
can cause an acquired immunodeficiency. Drugs used to fight
autoimmune diseases or prevent transplant rejection suppress Some viruses avoid an immune response by infecting cells
the immune system, leading to an immunodeficient state. and then entering a largely inactive state called latency.
Certain cancers also suppress the immune system, especially In latency, the production of most viral proteins and free
Hodgkin’s disease, which damages the lymphatic system. viruses ceases; as a result, latent viruses do not trigger an
Acquired immunodeficiencies range from temporary states adaptive immune response. Nevertheless, the viral genome
that may arise from physiological stress to the devastating persists in the nuclei of infected cells, either as a separate
disease AIDS (acquired immune deficiency syndrome), which DNA molecule or as a copy integrated into the host genome.
we’ll explore in the next section. Latency typically persists until conditions arise that are
favorable for viral transmission or unfavorable for host
Evolutionary Adaptations of Pathogens survival, such as when the host is infected by another
That Underlie Immune System Avoidance pathogen. Such circumstances trigger the synthesis and
release of free viruses that can infect new hosts.
Evolution Just as immune systems that ward off pathogens
have evolved in animals, mechanisms that thwart immune Herpes simplex viruses, which establish themselves in
responses have evolved in pathogens. Using human patho- human sensory neurons, provide a good example of latency.
gens as examples, we’ll examine some common mechanisms: The type 1 virus causes most oral herpes infections, whereas
antigenic variation, latency, and direct attack on the immune the type 2 virus is responsible for most cases of genital herpes.
system. Because sensory neurons express relatively few MHC I mol-
ecules, the infected cells are inefficient at presenting viral
Antigenic Variation antigens to circulating lymphocytes. Stimuli such as fever,
emotional stress, or menstruation reactivate the virus to rep-
One mechanism for escaping the body’s defenses is for a licate and infect surrounding epithelial tissues. Activation
pathogen to alter how it appears to the immune system. of the type 1 virus can result in blisters around the mouth
Immunological memory is a record of the foreign epitopes that are called “cold” sores. The type 2 virus can cause geni-
an animal has encountered. If the pathogen that expressed tal sores, but people infected with either the type 1 or type 2
those epitopes no longer does so, it can reinfect or remain in virus often have no symptoms. Infections of the type 2 virus,
a host without triggering the rapid and robust response that which is sexually transmitted, pose a serious threat to the
memory cells provide. Such changes in epitope expression babies of infected mothers and can increase transmission of
are called antigenic variation. The parasite that causes sleep- the virus that causes AIDS.
ing sickness (trypanosomiasis) provides an extreme example,
periodically switching at random among 1,000 versions of Attack on the Immune System: HIV
the protein found over its entire surface. In the Scientific
Skills Exercise, you’ll interpret data on this form of antigenic The human immunodeficiency virus (HIV), the patho-
variation and the body’s response. gen that causes AIDS, both escapes and attacks the adaptive
immune response. Once introduced into the body, HIV infects
Antigenic variation is the main reason the influenza, helper T cells with high efficiency by binding specifically to
or “flu,” virus remains a major public health problem. As the CD4 accessory protein (see Figure 43.17). HIV also infects
it replicates in one human host after another, the virus some cell types that have low levels of CD4, such as macro-
undergoes frequent mutations. Because any change that phages and brain cells. Inside cells, the HIV RNA genome is
lessens recognition by the immune system provides a selec- reverse-transcribed, and the product DNA is integrated into
tive advantage, the virus steadily accumulates mutations the host cell’s genome (see Figure 19.8). In this form, the viral
that change its surface proteins, reducing the effectiveness genome can direct the production of new viruses.
of the host immune response. As a result, a new flu vaccine
must be developed, produced, and distributed each year. Although the body responds to HIV with an immune
In addition, the human influenza virus occasionally forms response sufficient to eliminate most viral infections, some
new strains by exchanging genes with influenza viruses HIV invariably escapes. One reason HIV persists is that it has
that infect domesticated animals, such as pigs or chickens. a very high mutation rate. Altered proteins on the surface of
When this exchange of genes occurs, the new strain may some mutated viruses reduce interaction with antibodies and
not be recognized by any of the memory cells in the cytotoxic T cells. Such viruses replicate and mutate further.
human population. The resulting outbreak can be deadly: HIV thus evolves within the body. The continued presence of
The 1918–1919 influenza outbreak killed more than HIV is also helped by latency while the viral DNA is integrated
20 million people. in the host cell’s genome. This latent DNA is shielded from the
immune system as well as from antiviral agents currently used
against HIV, which attack only actively replicating viruses.

970 unit seven  Animal Form and Function

Scientific Skills Exercise 3. Assume that a drop in parasite abundance reflects an effective
immune response by the host. Formulate a hypothesis to explain
Comparing Two Variables the pattern you described in question 2.
on a Common x-Axis
Part B: Data from a Study of Antibody Levels  Many decades
How Does the Immune System Respond to a Changing after scientists first observed the pattern of Trypanosoma abundance
Pathogen?  Natural selection favors parasites that are able to main- over the course of infection, researchers identified antibodies specific
tain a low-level infection in a host for a long time. Trypanosoma, to different forms of the parasite’s surface glycoprotein. The table
the unicellular parasite that causes sleeping sickness, is one example. below lists the relative abundance of two such antibodies during
The glycoproteins covering a trypanosome’s surface are encoded by the early period of chronic infection, using an index ranging from
a gene that is duplicated more than 1,000 times in the organism’s 0 (absent) to 1.
genome. Each copy is slightly different. By periodically switching
among these genes, the trypanosome can display a series of surface Antibody Specific Antibody Specific
glycoproteins with different molecular structures. In this exercise, to Glycoprotein to Glycoprotein
you will interpret two data sets to explore hypotheses about the Day Variant A Variant B
benefits of the trypanosome’s ever-shifting surface glycoproteins
and the host’s immune response.  4 0 0
 6 0 0
Part A: Data from a Study of Parasite Levels This study mea-  8 0.2 0
sured the abundance of parasites in the blood of one human patient 10 0.5 0
during the first few weeks of a chronic infection. 12 1 0
14 1 0.1
Number of Parasites (in millions) 16 1 0.3
Day per mL of Blood 18 1 0.9
 4 0.1 20 1 1
 6 0.3 22 1 1
 8 1.2 24 1 1
10 0.2
12 0.2 Part B: Interpret The Data
14 0.9
16 0.6 4. Note that these data were collected over the same period
18 0.1 of infection (days 4–24) as the parasite abundance data you
20 0.7 graphed in part A. Therefore, you can incorporate these new
22 1.2 data into your first graph, using the same x-axis. However,
24 0.2 since the antibody level data are measured in a different way
than the parasite abundance data, add a second set of y-axis
Part A: Interpret The Data labels on the right side of your graph. Then, using different
1. Plot the data in the above table as a line graph. Which column is colors or sets of symbols, add the data for the two antibody
types. Labeling the y-axis two different ways enables you to
the independent variable, and which is the dependent variable? compare how two dependent variables change relative to a
Put the independent variable on the x-axis. (For additional shared independent variable.
information about graphs, see the Scientific Skills Review in
Appendix F.) 5. Describe any patterns you observe by comparing the two data sets
2. Visually displaying data in a graph can help make patterns in over the same period. Do these patterns support your hypothesis
the data more noticeable. Describe any patterns revealed by from part A? Do they prove that hypothesis? Explain.
your graph.
6. Scientists can now also distinguish the abundance of trypano-
somes recognized specifically by antibodies type A and
type B. How would incorporating such information change
your graph?

Instructors: A version of this Scientific Skills Exercise
can be assigned in MasteringBiology.

Data from  L. J. Morrison et al., Probabilistic order in antigenic variation of Trypanosoma
brucei, International Journal for Parasitology 35:961–972 (2005); and L. J. Morrison et al.,
Antigenic variation in the African trypanosome: molecular mechanisms and phenotypic
complexity, Cellular Microbiology 1:1724–1734 (2009).

chapter 43  The Immune System 971

Figure 43.27  The progress of an untreated HIV infection. of developing Kaposi’s sarcoma is 20,000 times greater for

Latency AIDS untreated AIDS patients than for healthy people. This obser-

vation was at first puzzling. If the immune system recognizes

Relative anti-HIV antibody only nonself, it should fail to recognize the uncontrolled
800 concentration
Helper T cell concentration growth of self cells that is the hallmark of cancer. It turns
in blood (cells/mm3)
out, however, that viruses are involved in about 15–20% of

600 Relative HIV all human cancers. Because the immune system can recog-
concentration
nize viral proteins as foreign, it can act as a defense against
Helper T cell
400 concentration viruses that can cause cancer and against cancer cells that

harbor viruses. A vaccine introduced in 1986 for hepatitis B

virus helps prevent liver cancer, the first cancer for which a

200 human vaccine became available.

In the 1970s, Harald zur Hausen, working in Heidelberg,

0 Germany, proposed that human papillomavirus (HPV) causes
0123456789
Years after untreated infection 10 cervical cancer. Many scientists were skeptical that cancer

Animation: HIV Reproductive Cycle could result from infection by HPV, the most common sexually
Interview with Flossie Wong-Staal: Characterizing HIV
transmitted pathogen. However, after more than a decade of

work, zur Hausen isolated two

particular types of HPV from Figure 43.28  Human
patients with cervical cancer. papillomavirus

Over time, an untreated HIV infection not only avoids He quickly made samples
the adaptive immune response but also abolishes it
(Figure 43.27). Viral replication and cell death triggered available to other scientists,
by the virus lead to loss of helper T cells, impairing both
humoral and cell-mediated immune responses. The even- leading in 2006 to the devel-
tual result is acquired immunodeficiency syndrome
(AIDS), an impairment in immune responses that leaves opment of highly effective
the body susceptible to infections and cancers that a
healthy immune system would usually defeat. For example, vaccines against HPV. The
Pneumocystis jirovecii, a common fungus that does not cause
disease in healthy individuals, can result in severe pneu- computer graphic image of an
monia in people with AIDS. Such opportunistic diseases,
as well as nerve damage and body wasting, are the primary HPV particle in Figure 43.28
causes of death in AIDS patients, rather than HIV itself.
illustrates the abundant copies
Transmission of HIV requires the transfer of virus particles
or infected cells from person to person via body fluids such as of the capsid protein (yellow)
semen, blood, or breast milk. Unprotected sex (that is, with-
out using a condom) and transmission via HIV-contaminated that is used as the antigen in
needles (typically among intravenous drug users) cause the
vast majority of HIV infections. The virus can enter the body vaccination.
through mucosal linings of the vagina, vulva, penis, or rec-
tum during intercourse or via the mouth during oral sex. Cervical cancer kills more than 4,000 women annually in
People infected with HIV can transmit the disease in the first
few weeks of infection, before they produce HIV-specific anti- the United States and is the fifth-most common cause of can-
bodies that can be detected in a blood test. Currently, 10–50%
of all new HIV infections appear to be caused by recently cer deaths among women worldwide. Administering an HPV
infected individuals. Although no cure has been found for
HIV infection, drugs that can significantly slow HIV replica- vaccine, either Gardasil or Cervarix, to young adults greatly
tion and the progression to AIDS have been developed.
reduces their chance of being infected with the HPV viruses
Cancer and Immunity
that cause cervical and oral cancers, as well as genital warts.
When adaptive immunity is inactivated, the frequency of
certain cancers increases dramatically. For example, the risk In 2008, zur Hausen shared the Nobel Prize in Physiology

or Medicine for his discovery.

Interview with Harald zur Hausen: Discovering the cause
of cervical cancer (see the interview before Chapter 40)

Concept Check 43.4

1. In the muscular disease myasthenia gravis, antibodies
bind to and block certain receptors on muscle cells, pre-
venting muscle contraction. Is this disease best classified
as an immunodeficiency disease, an autoimmune disease,
or an allergic reaction? Explain.

2. People with herpes simplex type 1 viruses often get
mouth sores when they have a cold or similar infection.
How might this location benefit the virus?

3. WHAT IF? How would a macrophage deficiency likely
affect a person’s innate and adaptive defenses?
For suggested answers, see Appendix A.

972 unit seven  Animal Form and Function

43 Chapter Review Go to MasteringBiology™ for Videos, Animations, Vocab Self-Quiz,
Practice Tests, and more in the Study Area.
Summary of Key Concepts
The four major characteristics of B and T cell development are
Concept  43.1 the generation of cell diversity, self-tolerance, proliferation, and
immunological memory. Proliferation and memory are both
In innate immunity, recognition and based on clonal selection, illustrated here for B cells:
Stem cell
response rely on traits common to Cell division and
gene rearrangement
groups of pathogens (pp. 951–956) VOCAB
SELF-QUIZ
In both invertebrates and vertebrates, innate goo.gl/6u55ks
immunity is mediated by physical and chemi-
cal barriers as well as cell-based defenses. Activation of innate
immune responses relies on recognition proteins specific for
broad classes of pathogens. Pathogens that penetrate barrier Elimination of
defenses are ingested by phagocytic cells, which in vertebrates self-reactive
include macrophages and dendritic cells. Additional B cells
cellular defenses include natural killer cells, which can Antigen
induce the death of virus-infected cells. Complement system
proteins, interferons, and other antimicrobial peptides also Clonal
act against pathogens. In the inflammatory response, selection
histamine and other chemicals that are released at the injury
site promote changes in blood vessels that enhance immune
cell access.
Pathogens sometimes evade innate immune defenses. For example,
some bacteria have an outer capsule that prevents recognition,
while others are resistant to breakdown within lysosomes. Formation of
activated cell Antibody
populations
? In what ways does innate immunity protect the mammalian
digestive tract?

Concept  43.2 Memory B cells Plasma cells
Pathogen
In adaptive immunity, receptors provide
pathogen-specific recognition (pp. 956–961)

Adaptive immunity relies on two types of lymphocytes that Receptors bind to antigens

arise from stem cells in the bone marrow: B cells and T cells. ? Why is the adaptive immune response to an initial infection slower than
Lymphocytes have cell-surface antigen receptors for foreign the innate response?
molecules (antigens). All receptor proteins on a single B or
T cell are the same, but there are millions of B and T cells in the
body that differ in the foreign Concept  43.3
molecules that their receptors Antigen
recognize. Upon infection, B and receptor Adaptive immunity defends against
infection of body fluids and body cells
T cells specific for the pathogen (pp. 961–968)
are activated. Some T cells help
other lymphocytes; others kill
infected host cells. B cells called Helper T cells interact with antigen fragments displayed by
plasma cells produce soluble B cell class II MHC molecules on the surface of antigen-presenting
cells: dendritic cells, macrophages, and B cells. Activated helper
proteins called antibodies, T cells secrete cytokines that stimulate other lymphocytes. In
which bind to foreign molecules the cell-mediated immune response, activated cytotoxic
and cells. Activated B and T cells Antigen Epitope T cells trigger destruction of infected cells. In the humoral
immune response, antibodies help eliminate antigens by
called memory cells defend promoting phagocytosis and complement-mediated lysis.
against future infections by the
Pathogen Active immunity develops in response to infection or to
immunization. The transfer of antibodies in passive
same pathogen. immunity provides immediate, short-term protection.
Recognition of foreign molecules by B cells and T cells involves
the binding of variable regions of receptors to an epitope, a Tissues or cells transferred from one person to another are subject
small region of an antigen. B cells and antibodies recognize to immune rejection. In tissue grafts and organ transplants, MHC
epitopes on the surface of antigens circulating in the blood or molecules stimulate rejection. Lymphocytes in bone marrow
lymph. T cells recognize epitopes in small antigen fragments transplants may cause a graft-versus-host reaction.
(peptides) that are presented on the surface of host cells by
proteins called major histocompatibility complex (MHC)
molecules This interaction activates a T cell, enabling it to ?
participate in adaptive immunity. Is immunological memory after a natural infection fundamentally
different from immunological memory after vaccination? Explain.

chapter 43  The Immune System 973

Concept  43.4 Level 3: Synthesis/Evaluation

Disruptions in immune system function 6. Vaccination increases the number of
can elicit or exacerbate disease (A) different receptors that recognize a pathogen.
(pp. 968–972) (B) lymphocytes with receptors that can bind to the pathogen.
(C) epitopes that the immune system can recognize.
In allergies, such as hay fever, the interaction of antibodies and (D) MHC molecules that can present an antigen.
allergens triggers immune cells to release histamine and other
mediators that cause vascular changes and allergic symptoms. 7. Which of the following would not help a virus avoid triggering
Loss of self-tolerance can lead to autoimmune diseases, an adaptive immune response?
such as multiple sclerosis. Inborn immunodeficiencies (A) having frequent mutations in genes for surface proteins
result from defects that interfere with innate, humoral, or cell- (B) infecting cells that produce very few MHC molecules
mediated defenses. AIDS is an acquired immunodeficiency (C) producing proteins very similar to those of other viruses
caused by HIV. (D) infecting and killing helper T cells

Antigenic variation, latency, and direct assault on the immune 8. DRAW IT  Consider a pencil-shaped protein with two epitopes,
system allow some pathogens to thwart immune responses. HIV Y (the “eraser” end) and Z (the “point” end). They are
infection destroys helper T cells, leaving the patient prone to recognized by antibodies A1 and A2, respectively. Draw and
disease. Immune defense against cancer appears to primarily label a picture showing the antibodies linking proteins into a
involve action against viruses that can cause cancer and cancer complex that could trigger endocytosis by a macrophage.
cells that harbor viruses.
9. MAKE CONNECTIONS  Contrast clonal selection with
? Is being infected with HIV the same as having AIDS? Explain. Lamarck’s idea for the inheritance of acquired characteristics
(see Concept 22.1).
Test Your Understanding
10. EVOLUTION CONNECTION  Describe one invertebrate
Level 1: Knowledge/Comprehension mechanism of defense against pathogens and discuss how it is
an evolutionary adaptation retained in vertebrates.
1. Which of these is not part of insect immunity? PRACTICE
(A) enzyme activation of pathogen-killing TEST 11. SCIENTIFIC INQUIRY  A major cause of septic shock is the
chemicals presence of lipopolysaccharide (LPS) from bacteria in the blood.
(B) activation of natural killer cells goo.gl/CUYGKD Suppose you have available purified LPS and several strains of
(C) phagocytosis by hemocytes mice, each with a mutation that inactivates a particular TLR
(D) production of antimicrobial peptides gene. How might you use these mice to test the feasibility of
treating septic shock with a drug that blocks TLR signaling?
2. An epitope associates with which part of an antigen receptor
or antibody? 12. WRITE ABOUT A THEME: INFORMATION  Among all
(A) the tail nucleated body cells, only B and T cells lose DNA during their
(B) the heavy-chain constant regions only development and maturation. In a short essay (100–150 words),
(C) variable regions of a heavy chain and light chain discuss the relationship between this loss and DNA as heritable
combined biological information, focusing on similarities between
(D) the light-chain constant regions only cellular and organismal generations.

3. Which statement best describes the difference between 13. Synthesize Your Knowledge
responses of effector B cells (plasma cells) and those of
cytotoxic T cells? This photo shows a child receiving an oral vaccine against
(A) B cells confer active immunity; cytotoxic T cells confer polio, a disease caused by a virus that infects neurons. Given
passive immunity. that the body cannot readily replace most neurons, why is
(B) B cells respond the first time a pathogen is present; it important that a polio vaccine stimulate not only a
cytotoxic T cells respond subsequent times. cell-mediated response but also a humoral response?
(C) B cells secrete antibodies against a pathogen; cytotoxic For selected answers, see Appendix A.
T cells kill pathogen-infected host cells.
(D) B cells carry out the cell-mediated response; cytotoxic For additional practice questions, check out the Dynamic Study
T cells carry out the humoral response. Modules in MasteringBiology. You can use them to study on
your smartphone, tablet, or computer anytime, anywhere!
Level 2: Application/Analysis

4. Which of the following statements is not true?
(A) An antibody has more than one antigen-binding site.
(B) A lymphocyte has receptors for multiple different
antigens.
(C) An antigen can have different epitopes.
(D) A liver or muscle cell makes one class of MHC molecule.

5. Which of the following should be the same in
identical twins?
(A) the set of antibodies produced
(B) the set of MHC molecules produced
(C) the set of T cell antigen receptors produced
(D) the set of immune cells eliminated as self-reactive

974 unit seven  Animal Form and Function

44Osmoregulation and Excretion

Figure 44.1  How does an albatross drink salt water without ill effect?

Key Concepts A Balancing Act

44.1 Osmoregulation balances At 3.5 m, the wingspan of a wandering albatross (Diomedea exulans) is the largest of
any living bird. But the albatross commands attention for more than just its size.
the uptake and loss of water This massive bird remains at sea day and night throughout the year, returning to
and solutes land only to reproduce. A human with only seawater to drink would die of dehydra-
tion, but faced with the same conditions, the albatross thrives (Figure 44.1).
44.2 An animal’s nitrogenous wastes
For both albatross and human, maintaining the fluid balance of their tissues
reflect its phylogeny and habitat requires that the relative concentrations of water and solutes be kept within fairly
narrow limits. In addition, ions such as sodium and calcium must be maintained
44.3 Diverse excretory systems are at concentrations that permit normal activity of muscles, neurons, and other
body cells. Homeostasis thus requires osmoregulation, the general term for the
variations on a tubular theme processes by which animals control solute concentrations and balance water gain
and loss.
44.4 The nephron is organized for
A number of mechanisms for water and solute control have arisen during evo-
stepwise processing of blood lution, reflecting the varied and often severe osmoregulatory challenges presented
filtrate by an animal’s surroundings. Animals living in the arid conditions of a desert, for
instance, can quickly lose body water. So too can albatrosses and other marine
44.5 Hormonal circuits link kidney animals. Survival in these dehydrating environments depends on conserving body

function, water balance, and water and, for marine birds and fishes, eliminating excess salts. Freshwater
blood pressure animals face a distinct challenge: a watery environment that threatens

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and go to the Study Area for digital resources.

975

to dilute their body fluids. These organisms survive by con- membrane at equal rates in both directions. Thus, there is no
serving solutes and absorbing salts from their surroundings. net movement of water by osmosis between isoosmotic solu-
tions. When two solutions differ in osmolarity, the solution
In safeguarding their internal fluids, animals must deal with the higher concentration of solutes is said to be hyperos-
with ammonia, a toxic metabolite produced by the disman- motic, and the more dilute solution is said to be hypoosmotic.
tling of nitrogenous (nitrogen-containing) molecules, chiefly Water flows by osmosis from a hypoosmotic solution to a
proteins and nucleic acids. Several mechanisms have evolved hyperosmotic one, thus reducing the concentration differ-
for ridding the body of nitrogenous metabolites and other ence for both solutes and free water (see Figure 44.2).
metabolic waste products, a process called excretion. Because
systems for excretion and osmoregulation are structurally and In this chapter, we use the terms isoosmotic, hypoosmotic,
functionally linked in many animals, we’ll consider both of and hyperosmotic, which refer specifically to osmolarity,
these processes in this chapter. instead of isotonic, hypotonic, and hypertonic. The latter set of
terms applies to the response of animal cells—whether they
Concept  44.1 swell or shrink—in solutions of known solute concentrations.

Osmoregulation balances the uptake Osmoregulatory Challenges
and loss of water and solutes and Mechanisms

Just as thermoregulation depends on balancing heat loss and An animal can maintain water balance in two ways. One is to
gain (see Concept 40.3), regulating the chemical composition be an osmoconformer: to be isoosmotic with its surround-
of body fluids depends on balancing the uptake and loss of ings. All osmoconformers are marine animals. Because an
water and solutes. If water uptake is excessive, animal cells osmoconformer’s internal osmolarity is the same as that of
swell and burst; if water loss is substantial, cells shrivel and its environment, there is no tendency to gain or lose water.
die. Ultimately, the driving force for the movement of both Many osmoconformers live in water that has a stable compo-
water and solutes—in animals as in all other organisms—is sition and hence have a constant internal osmolarity.
a concentration gradient of one or more solutes across the
plasma membrane. The second way to maintain water balance is to be an
osmoregulator: to control internal osmolarity independent
Osmosis and Osmolarity of that of the external environment. Osmoregulation enables
animals to live in environments that are uninhabitable for
Water enters and leaves cells by osmosis, which occurs when osmoconformers, such as freshwater and terrestrial habitats,
two solutions separated by a membrane differ in total solute or to move between marine and freshwater environments
concentration (Figure 44.2). The unit of measurement for (Figure 44.3).
solute concentration is osmolarity, the number of moles of
solute per liter of solution. The osmolarity of human blood is In a hypoosmotic environment, an osmoregulator must
about 300 milliosmoles per liter (mOsm/L), whereas that of discharge excess water. In a hyperosmotic environment, it must
seawater is about 1,000 mOsm/L. instead take in water to offset osmotic loss. Osmoregulation
allows many marine animals to maintain an internal osmolar-
Two solutions with the same osmolarity are said to be ity different from that of seawater.
isoosmotic. If a selectively permeable membrane separates
the solutions, water molecules will continually cross the Figure 44.3  Sockeye salmon (Oncorhynchus nerka),
osmoregulators that migrate between rivers and the ocean.

Figure 44.2  Solute concentration and osmosis.

Selectively permeable
membrane

Solutes Water

Hyperosmotic side: Hypoosmotic side:
• Higher solute • Lower solute

concentration concentration
• Lower free H2O • Higher free H2O

concentration concentration

Net water flow
976 Unit seven  Animal Form and Function

Whether osmoconformers or osmoregulators, most animals Eliminating urea is important because high concentrations
cannot tolerate substantial changes in external osmolarity and of urea can denature (unfold) proteins and thus disrupt cel-
are said to be stenohaline (from the Greek stenos, narrow, and lular functions. Sharks, however, have a high concentration
halos, salt). In contrast, euryhaline animals (from the Greek eurys, of urea in their body. Why isn’t urea toxic for these animals?
broad) can survive large fluctuations in external osmolarity. The answer lies in an organic molecule, trimethylamine oxide
Euryhaline osmoconformers include barnacles and mussels in (TMAO), produced by shark tissues. TMAO protects proteins
estuaries that are alternately exposed to fresh and salt water; from the denaturing effect of urea.
euryhaline osmoregulators include striped bass and the various
species of salmon (see Figure 44.3). TMAO has another function in sharks: osmoregulation.
Like bony fishes, sharks have an internal salt concentration
Next we’ll examine adaptations for osmoregulation that much lower than that of seawater. Thus, salt tends to diffuse
have evolved in marine, freshwater, and terrestrial animals. from the water into their bodies, especially across their gills.
However, the combination of TMAO with salts, urea, and
Marine Animals other compounds results in a solute concentration in shark
tissues that is actually somewhat higher than 1,000 mOsm/L.
Most marine invertebrates are osmoconformers. Their osmo- For this reason, water slowly enters the shark’s body by osmo-
larity is the same as that of seawater. Therefore, they face sis and in food (sharks do not drink).
no substantial challenges in water balance. Nevertheless,
they actively transport specific solutes that establish levels in The small influx of water into the shark’s body is disposed
hemolymph (circulatory fluid) different from those in the of in urine produced by the kidneys. The urine also removes
ocean. For example, homeostatic mechanisms in the Atlantic some of the salt that diffuses into the shark’s body; the rest
lobster (Homarus americanus) maintain a magnesium ion is lost in feces or is secreted from a specialized gland.
(Mg2+) concentration of less than 9 mM (millimolar, or
10-3 mol/L), far below the 50 mM concentration of Mg2+ in Freshwater Animals
their environment.
The osmoregulatory problems of freshwater animals are
Two osmoregulatory strategies evolved among marine the opposite of those of marine animals. The body fluids of
vertebrates that address the challenges of a strongly dehydrat- freshwater animals must be hyperosmotic because animal
ing environment. One is found among marine “bony fishes,” cells cannot tolerate salt concentrations as low as that of
a group that includes ray-finned and lobe-finned fishes. The lake or river water. Since freshwater animals have internal
other is found in marine sharks and most other chondrich- fluids with an osmolarity higher than that of their surround-
thyans (cartilaginous animals; see Concept 34.3). ings, they face the problem of gaining water by osmosis.
In many freshwater animals, including bony fishes such as
Cod, shown in Figure 44.4a, and other marine bony fishes the perch, shown in Figure 44.4b, water balance relies on
constantly lose water by osmosis. They balance water loss by excreting large amounts of very dilute urine and drinking
drinking a lot of seawater. The excess salts ingested with sea- almost no water. In addition, salts lost by diffusion and in
water are eliminated through the gills and kidneys. the urine are replenished by eating and by salt uptake across
their gills.
As noted earlier, osmoregulation is frequently coupled
to elimination of nitrogenous waste products, such as urea.

Figure 44.4  Osmoregulation in marine and freshwater bony fishes: a comparison.

(a) Osmoregulation in a marine fish (b) Osmoregulation in a freshwater fish

Gain of water and Excretion Osmotic water Gain of water and Uptake Osmotic water
salt ions from food of salt ions loss through gills some ions in food of salt ions gain through gills
from gills and other parts by gills and other parts
of body surface of body surface

SALT WATER Key FRESH WATER
Excretion of salt ions and
Gain of water small amounts of water in Water Excretion of salt ions and
and salt ions from scanty urine from kidneys Salt large amounts of water in
drinking seawater dilute urine from kidneys

chapter 44  Osmoregulation and Excretion 977

Salmon and other euryhaline fishes that migrate between with proteins and membrane lipids. Many insects that sur-
fresh water and seawater undergo dramatic changes in osmo- vive freezing in the winter also use trehalose as a membrane
regulatory status. When living in rivers and streams, salmon protectant, as do some plants resistant to desiccation.
osmoregulate like other freshwater fishes, producing large
amounts of dilute urine and taking up salt from the dilute Recently, scientists began applying lessons learned from
environment through their gills. When they migrate to the the study of anhydrobiosis to the preservation of biological
ocean, salmon acclimatize (see Concept 40.2). They produce materials. Traditionally, samples of protein, DNA, and cells
more of the steroid hormone cortisol, which increases the have been kept in ultracold freezers (-80°C), consuming large
number and size of specialized salt-secreting cells. As a result amounts of energy and space. Now, however, the manu-
of these and other physiological changes, salmon in salt facture of materials modeled after the protectants found in
water excrete excess salt from their gills and produce only anhydrobiotic species has enabled such samples to be stored
small amounts of urine—just like bony fishes that spend in compact chambers at room temperature.
their entire lives in salt water.
Land Animals
Animals That Live in Temporary Waters
The threat of dehydration is a major regulatory problem for
Extreme dehydration, or desiccation, is fatal for most animals. terrestrial plants and animals. Adaptations that reduce water
However, a few aquatic invertebrates that live in temporary loss are key to survival on land. Much as a waxy cuticle con-
ponds and in films of water around soil particles can lose tributes to the success of land plants, the body coverings of
almost all their body water and survive. These animals enter most terrestrial animals help prevent dehydration. Examples
a dormant state when their habitats dry up, an adaptation are the waxy layers of insect exoskeletons, the shells of land
called anhydrobiosis (“life without water”). Among the snails, and the layers of dead, keratinized skin cells covering
most striking examples are the tardigrades, or water bears, most terrestrial vertebrates, including humans. Many terres-
tiny invertebrates less than 1 mm long (Figure 44.5). In trial animals, especially desert-dwellers, are nocturnal, which
their active, hydrated state, they contain about 85% water by reduces evaporative water loss because of the lower tempera-
weight, but they can dehydrate to less than 2% water and sur- ture and higher humidity of night air.
vive in an inactive state, dry as dust, for a decade or more. Just
add water, and within hours the rehydrated tardigrades are Despite these and other adaptations, most terrestrial ani-
moving about and feeding. mals lose water through many routes: in urine and feces,
across the skin, and from the surfaces of gas exchange organs.
Anhydrobiosis requires adaptations that keep cell mem- Land animals maintain water balance by drinking and eating
branes intact. Researchers are just beginning to learn how moist foods and by producing water metabolically through
tardigrades survive drying out, but studies of anhydrobiotic cellular respiration.
roundworms (phylum Nematoda; see Concept 33.4) show
that desiccated individuals contain large amounts of sugars. A number of desert animals are well enough adapted for
In particular, a disaccharide called trehalose seems to protect minimizing water loss that they can survive for long periods of
the cells by replacing the water that is normally associated time without drinking. Camels, for example, tolerate a 7°C rise
in body temperature, greatly reducing the amount of water
Figure 44.5  Anhydrobiosis. Tardigrades (SEM images) inhabit lost in sweat production. Also, they can lose 25% of their
temporary ponds as well as droplets of water in soil and on moist plants. body water and survive. (In contrast, a human who loses half
this amount of body water will die from heart failure.) In the
50 μm Scientific Skills Exercise, you can examine water balance in
another desert species, the sandy inland mouse.
Hydrated tardigrade Dehydrated
tardigrade Energetics of Osmoregulation

Maintaining an osmolarity difference between an animal’s
body and its external environment carries an energy cost.
Because diffusion tends to equalize concentrations in a sys-
tem, osmoregulators must expend energy to maintain the
osmotic gradients that cause water to move in or out. They
do so by using active transport to manipulate solute concen-
trations in their body fluids.

The energy cost of osmoregulation depends on how dif-
ferent an animal’s osmolarity is from its surroundings, how
easily water and solutes can move across the animal’s surface,
and how much work is required to pump solutes across the

978 Unit seven  Animal Form and Function

Scientific Skills Exercise

Describing and Interpreting
Quantitative Data

How Do Desert Mice Maintain Osmotic Homeostasis? The
sandy inland mouse (now known as Pseudomys hermannsburgensis)
is an Australian desert mammal that can survive indefinitely on a diet
of dried seeds without drinking water. To study this species’ adapta-
tions to its arid environment, researchers conducted a laboratory
experiment in which they controlled access to water. In this exercise,
you will analyze some of the data from the experiment.

How the Experiment Was Done  Nine captured mice were kept in Interpret The Data
an environmentally controlled room and given birdseed (10% water
by weight) to eat. In part A of the study, the mice had unlimited access 1. In words, describe how the data differ between the unlimited
to tap water for drinking; in part B of the study, the mice were not water and no-water conditions for the following: (a) osmolarity
given any drinking water for 35 days, similar to conditions in their of urine, (b) osmolarity of blood, (c) urea concentration in urine,
natural habitat. At the end of parts A and B, the researchers measured (d) urea concentration in blood. (e) Does this data set provide
the osmolarity and urea concentration of the urine and blood of each evidence of homeostatic regulation? Explain.
mouse. The mice were also weighed three times a week.
2. (a) Calculate the ratio of urine osmolarity to blood osmolarity for
Data from the Experiment mice with unlimited access to water. (b) Calculate this ratio for
mice with no access to water. (c) What conclusion would you
Access to Mean Osmolarity Mean Urea draw from these ratios?
Water (mOsm/L) Concentration (mM)
3. If the amount of urine produced were different in the two
Urine Blood Urine Blood conditions, how would that affect your calculation? Explain.

Part A:     490 350     330 7.  6 Instructors: A version of this Scientific Skills Exercise can be
assigned in MasteringBiology.
Unlimited
Data from  R. E. MacMillen et al., Water economy and energy metabolism of the
Part B: None 4,700 320 2,700 11 sandy inland mouse, Leggadina hermannsburgensis, Journal of Mammalogy 53:
529–539 (1972).
In part A, the mice drank about 33% of their body weight each day.
The change in body weight during the study was negligible for all mice.

membrane. Osmoregulation accounts for 5% or more of the by managing the solute content of an internal body fluid
resting metabolic rate of many fishes. For brine shrimp, small that bathes the cells. In insects and other animals with
crustaceans that live in extremely salty lakes, the gradient an open circulatory system, the fluid surrounding cells is
between internal and external osmolarity is very large, and hemolymph. In vertebrates and other animals with a closed
the cost of osmoregulation is correspondingly high—as much circulatory system, the cells are bathed in an interstitial
as 30% of the resting metabolic rate. fluid that contains a mixture of solutes controlled indirectly
by the blood. Maintaining the composition of such fluids
The energy cost to an animal of maintaining water and salt depends on structures ranging from individual cells that
balance is minimized by having body fluids that are adapted regulate solute movement to complex organs such as the
to the salinity of the animal’s habitat. Thus, the body fluids of vertebrate kidney.
most animals that live in fresh water (which has an osmolar-
ity of 0.5–15 mOsm/L) have lower solute concentrations than In most animals, osmoregulation and metabolic waste
the body fluids of their closest relatives that live in seawater disposal rely on transport epithelia—one or more layers
(1,000 mOsm/L). For instance, whereas marine molluscs have of epithelial cells specialized for moving particular solutes in
body fluids with solute concentrations of approximately 1,000 controlled amounts in specific directions. Transport epithelia
mOsm/L, some freshwater molluscs maintain the osmolarity of are typically arranged into tubular networks with extensive
their body fluids at just 40 mOsm/L. In each case, minimizing surface areas. Some transport epithelia face the outside envi-
the osmotic difference between body fluids and the surround- ronment directly, whereas others line channels connected to
ing environment decreases the energy cost of osmoregulation. the outside by an opening on the body surface.

Transport Epithelia in Osmoregulation The transport epithelium that enables the albatross and
other marine birds to survive on seawater remained undis-
The ultimate function of osmoregulation is to control solute covered for many years. To explore this question, researchers
concentrations in cells, but most animals do this indirectly gave captive marine birds only seawater to drink. Although

chapter 44  Osmoregulation and Excretion 979

very little salt appeared in the birds’ urine, fluid dripping Concept Check 44.1
from the tip of their beaks was a concentrated solution of
salt (NaCl). The source of this solution was a pair of nasal salt 1. The movement of salt from the surrounding water to the
glands packed with transport epithelia (Figure 44.6). Salt blood of a freshwater fish requires the expenditure of
glands, which are also found in sea turtles and marine igua- energy in the form of ATP. Why?
nas, use active transport of ions to secrete a fluid much saltier
than the ocean. Even though drinking seawater brings in a 2. Why aren’t any freshwater animals osmoconformers?
lot of salt, the salt gland enables these marine vertebrates to 3. WHAT IF? Researchers found that a camel in the sun
achieve a net gain of water. By contrast, humans who drink a
given volume of seawater must use a greater volume of water required much more water when its fur was shaved off,
to excrete the salt load, with the result that they become although its body temperature was the same. What can
dehydrated. you conclude about the relationship between osmoregu-
lation and the insulation provided by fur?
Transport epithelia that function in maintaining water
balance also often function in disposal of metabolic wastes. For suggested answers, see Appendix A.
We’ll see examples of this coordinated function in our
upcoming consideration of earthworm and insect excretory Concept  44.2
systems as well as the vertebrate kidney.
An animal’s nitrogenous wastes
Figure 44.6  Salt secretion in the nasal glands of a marine reflect its phylogeny and habitat
bird. A transport epithelium moves salt from the blood into secretory
tubules, which drain into central ducts leading to the nostrils. Because most metabolic wastes must be dissolved in water
to be excreted from the body, the type and quantity of an
Nostril animal’s waste products may have a large impact on its
with salt water balance. In this regard, some of the most significant
secretions waste products are the nitrogenous breakdown products of
proteins and nucleic acids. When proteins and nucleic acids
Nasal salt gland are broken apart for energy or converted to carbohydrates
or fats, enzymes remove nitrogen in the form of ammonia
Vein Artery Secretory Lumen of (NH3). Ammonia is very toxic, in part because its ion, ammo-
cell of secretory nium (NH4+), can interfere with oxidative phosphorylation.
transport tubule Although some animals excrete ammonia directly, many
epithelium species expend energy to convert it to less toxic compounds
prior to excretion.
Capillary Salt
Secretory tubule ions Forms of Nitrogenous Waste
Transport
epithelium Animals excrete nitrogenous wastes as ammonia, urea, or uric
acid (Figure 44.7). These different forms vary significantly in
Blood flow Salt secretion their toxicity and the energy costs of producing them.

Central duct Ammonia

Animals that excrete ammonia need access to lots of water
because ammonia can be tolerated only at very low concen-
trations. Therefore, ammonia excretion is most common
in aquatic species. The highly soluble ammonia molecules,
which interconvert between NH3 and NH4+ forms, easily pass
through membranes and are readily lost by diffusion to the
surrounding water. In many invertebrates, ammonia release
occurs across the whole body surface.

Urea

Although ammonia excretion works well in many aquatic
species, it is much less suitable for land animals. Ammonia
is so toxic that it can be safely transported through and
excreted from the body only in large volumes of very dilute
solutions. Most terrestrial animals and many marine species

980 Unit seven  Animal Form and Function

Figure 44.7  Variations in forms of nitrogenous waste While not primarily uric acid producers, humans and
among animal species. some other animals generate a small amount of uric acid from
metabolism. Diseases that alter this process reflect problems
Proteins Breakdown of nitrogen- Nucleic acids that can arise when a metabolic product is insoluble. For
Amino acids containing macromolecules Nitrogenous bases example, a genetic defect predisposes Dalmatian dogs to form
uric acid stones in their bladder. In humans, adult males are
Removal of nitrogen- particularly susceptible to gout, a painful joint inflamma-
containing amino group tion caused by deposits of uric acid crystals. Some dinosaurs
appear to have been similarly affected: Fossilized bones of
—NH2 Tyrannosaurus rex exhibit joint damage characteristic of gout.
(amino groups)
The Influence of Evolution and Environment
Conversion to nitrogenous waste O on Nitrogenous Wastes
HN C C HN
NH3 O C NH2 CO Evolution As a result of natural selection, the type and
NH2 C C amount of nitrogenous waste a species produces are matched
O N NH to its environment. One key factor in a habitat is the avail-
H ability of water. For example, terrestrial turtles (which often
live in dry areas) excrete mainly uric acid, whereas aquatic
Ammonia Urea Uric acid turtles excrete both urea and ammonia.

Most aquatic animals, Mammals, most Birds and many other In some cases, an animal’s egg is the immediate environ-
including most bony amphibians, sharks, reptiles, insects, land ment of relevance to the type of nitrogenous waste excreted.
fishes some bony fishes snails In an amphibian egg, which lacks a shell, ammonia or urea
can simply diffuse out of the egg. Similarly, soluble wastes
simply do not have access to sufficient water to routinely produced by a mammalian embryo can be carried away by
excrete ammonia. Instead, they mainly excrete a different the mother’s blood. In the case of birds and other reptiles,
nitrogenous waste, urea. In vertebrates, urea is the product however, the egg is surrounded by a shell that is permeable to
of an energy-consuming metabolic cycle that combines gases but not to liquids. As a result, any soluble nitrogenous
ammonia with carbon dioxide in the liver. wastes released by the embryo would be trapped within the
egg and could accumulate to dangerous levels. For this reason,
The main advantage of urea for nitrogenous waste excre- using uric acid as an insoluble waste product conveys a selec-
tion is its very low toxicity. The main disadvantage is its tive advantage in reptiles. Stored within the egg as a harmless
energy cost: Animals must expend energy to produce urea solid, the uric acid is left behind when the animal hatches.
from ammonia. From a bioenergetic standpoint, we would
predict that animals that spend part of their lives in water Regardless of the type of nitrogenous waste, the amount
and part on land would switch between excreting ammonia produced is coupled to the animal’s energy budget.
(thereby saving energy) and excreting urea (reducing excre- Endotherms, which use energy at high rates, eat more food
tory water loss). Indeed, many amphibians excrete mainly and produce more nitrogenous waste than ectotherms. The
ammonia when they are aquatic tadpoles and switch largely amount of nitrogenous waste is also linked to diet. Predators,
to urea excretion when they become land-dwelling adults. which derive much of their energy from protein, excrete
more nitrogen than animals that rely mainly on lipids or
Uric Acid carbohydrates as energy sources.

Insects, land snails, and many reptiles, including birds, Having surveyed the forms of nitrogenous waste and their
excrete uric acid as their primary nitrogenous waste. (Bird interrelationship with habitat and energy consumption, we’ll
droppings, or guano, are a mixture of white uric acid and turn next to the processes and systems animals use to excrete
brown feces.) Uric acid is relatively nontoxic and does not these and other wastes.
readily dissolve in water. It therefore can be excreted as a
semisolid paste with very little water loss. However, uric acid Concept Check 44.2
is even more energetically expensive than urea, requiring
considerable ATP for synthesis from ammonia. 1. What advantage does uric acid offer as a nitrogenous
waste in arid environments?

2. WHAT IF? Suppose a bird and a human both have
gout. Why might reducing purine in their diets help
the human much more than the bird?

For suggested answers, see Appendix A.

chapter 44  Osmoregulation and Excretion 981

Concept  44.3 as salts, sugars, amino acids, and nitrogenous wastes, cross
the membrane, forming a solution called the filtrate.
Diverse excretory systems are
variations on a tubular theme The filtrate is converted to a waste fluid by the specific
transport of materials into or out of the filtrate. The process
Whether an animal lives on land, in salt water, or in fresh of selective reabsorption recovers useful molecules and
water, water balance depends on the regulation of solute move- water from the filtrate and returns them to the body fluid.
ment between internal fluids and the external environment. Valuable solutes—including glucose, certain salts, vitamins,
Much of this movement is handled by excretory systems. hormones, and amino acids—are reabsorbed by active trans-
These systems are central to homeostasis because they dispose port. Nonessential solutes and wastes are left in the filtrate
of metabolic wastes and control body fluid composition. or are added to it by selective secretion, which also occurs
by active transport. The pumping of various solutes in turn
Excretory Processes determines whether water moves by osmosis into or out of the
filtrate. In the last step—excretion—the processed filtrate con-
Animals across a wide range of species produce a fluid waste taining nitrogenous wastes is released from the body as urine.
called urine through the basic steps shown in Figure 44.8.
In the first step, body fluid (blood, coelomic fluid, or hemo- Survey of Excretory Systems
lymph) is brought in contact with the selectively permeable
membrane of a transport epithelium. In most cases, hydro- The systems that perform the basic excretory functions vary
static pressure (blood pressure in many animals) drives a pro- widely among animal groups. However, they are generally
cess of filtration. Cells, as well as proteins and other large built on a complex network of tubules that provide a large
molecules, cannot cross the epithelial membrane and remain surface area for the exchange of water and solutes, including
in the body fluid. In contrast, water and small solutes, such nitrogenous wastes. We’ll examine the excretory systems of
flatworms, earthworms, insects, and vertebrates as examples
Figure 44.8  Key steps of excretory system function: of evolutionary variations on tubule networks.
an overview. Most excretory systems produce a filtrate by
pressure-filtering body fluids and then modify the filtrate’s contents. Protonephridia
This diagram is modeled after the vertebrate excretory system.
As illustrated in Figure 44.9, flatworms (phylum Platyhel­
minthes), which lack a coelom or body cavity, have excretory
systems called protonephridia (singular, protonephridium).

Capillary 1 Filtration. The excretory Figure 44.9  Protonephridia in a planarian.
tubule collects a filtrate from
the blood. Water and solutes Tubules of 1 Drawn by
are forced by blood pressure protonephridia beating cilia,
across the selectively interstitial fluid
Filtrate permeable membranes of a filters through the
cluster of capillaries and into membrane where
the excretory tubule. the cap cell and
tubule cell interlock.
Excretory 2 Filtrate
tubule empties into
the external
2 Reabsorption. The environment.
transport epithelium reclaims
valuable substances from the INTERSTITIAL
filtrate and returns them to FLUID
the body fluids.

3 Secretion. Other Cap Cilia
substances, such as toxins cell
and excess ions, are Flame
extracted from body fluids bulb Tubule
and added to the contents cell
of the excretory tubule.

Tubule

Urine 4 Excretion. The altered
filtrate (urine) leaves the
system and the body. Opening in
body wall

982 Unit seven  Animal Form and Function

Protonephridia consist of a network of dead-end tubules network. A ciliated funnel surrounds the internal opening of
that branch throughout the body. Cellular units called flame each metanephridium. As the cilia beat, fluid is drawn into a
bulbs cap the branches of each protonephridium. Each flame collecting tubule, which includes a storage bladder that opens
bulb, consisting of a tubule cell and a cap cell, has a tuft of to the outside.
cilia projecting into the tubule.
Earthworms inhabit damp soil and therefore usually
During filtration, the beating of the cilia draws water and experience a net uptake of water by osmosis through their
solutes from the interstitial fluid through the flame bulb, skin. Their metanephridia balance the water influx by pro-
releasing filtrate into the tubule network. (The name flame ducing urine that is dilute (hypoosmotic to body fluids). In
bulb derives from the moving cilia’s resemblance to a flicker- producing a hypoosmotic filtrate, the transport epithelium
ing flame.) The processed filtrate moves outward through the reabsorbs most solutes and returns them to the blood in
tubules and empties as urine via external openings. Because the capillaries. Nitrogenous wastes, however, remain in the
the urine excreted by freshwater flatworms is low in solutes, tubule and are excreted to the environment. The metane-
its production helps to balance the osmotic uptake of water phridia of an earthworm thus serve both an excretory and
from the environment. an osmoregulatory function.

Protonephridia are also found in rotifers, some annelids, Malpighian Tubules
mollusc larvae, and lancelets (see Figure 34.4). In the fresh-
water flatworms, protonephridia serve chiefly in osmoregula- Insects and other terrestrial arthropods have organs called
tion. Most metabolic wastes diffuse out of the animal across Malpighian tubules that remove nitrogenous wastes and
the body surface or are excreted into the gastrovascular cav- that also function in osmoregulation (Figure 44.11). The
ity and eliminated through the mouth (see Figure 33.10). In Malpighian tubules extend from dead-end tips immersed
contrast, parasitic flatworms that are isoosmotic to the sur- in hemolymph to openings into the digestive tract. The fil-
rounding fluids of their host organisms have protonephridia tration step common to other excretory systems is absent.
that primarily function in disposing of nitrogenous wastes. Instead, the transport epithelium that lines the tubules
Natural selection has thus adapted protonephridia to differ- secretes certain solutes, including nitrogenous wastes, from
ent tasks in different environments. the hemolymph into the lumen of the tubule. Water follows
the solutes into the tubule by osmosis.
Metanephridia
Figure 44.11  Malpighian tubules of insects. Malpighian
Most annelids, such as earthworms, have metanephridia tubules are outpocketings of the digestive tract that remove nitrogenous
(singular, metanephridium), excretory organs that collect fluid wastes and function in osmoregulation.
directly from the coelom (Figure 44.10). A pair of metane-
phridia are found in each segment of an annelid, where they Digestive tract
are immersed in coelomic fluid and enveloped by a capillary

Figure 44.10  Metanephridia of an earthworm. Each segment Rectum Hindgut
of the worm contains a pair of metanephridia, which collect coelomic Intestine
fluid from the adjacent anterior segment. The region highlighted in
yellow illustrates the organization of one metanephridium of a pair;
the other would be behind it.

Coelom Capillary Midgut Malpighian
network (stomach) tubules

Salt, water, and Feces and urine To anus
nitrogenous
wastes

Components of a Malpighian
metanephridium: tubule
Collecting tubule Rectum
Internal opening
Reabsorption of
Bladder H2O, ions, and
External opening valuable organic
molecules
HEMOLYMPH

chapter 44  Osmoregulation and Excretion 983

Figure 44.12  Exploring The Mammalian Excretory System

Excretory Organs Kidney Structure Nephron Types

Renal Cortical Juxtamedullary
cortex nephron nephron
Renal
medulla

Posterior Kidney Renal
vena cava artery
Renal artery Renal Renal
and vein vein cortex

Aorta

Ureter Ureter Renal
Urinary medulla
bladder
Urethra Renal pelvis

In humans, the excretory system consists Each kidney has an outer renal cortex Weaving back and forth across the renal
of kidneys, a pair of organs each about and an inner renal medulla. Both regions cortex and medulla are the nephrons,
10 cm in length, as well as organs for trans- are supplied with blood by a renal artery the functional units of the vertebrate kid-
porting and storing urine. Urine produced and drained by a renal vein. Within the ney. Of the roughly 1 million nephrons
by each kidney exits through a duct called cortex and medulla lie tightly packed excre- in a human kidney, 85% are cortical
the ureter; the two ureters drain into a tory tubules and associated blood vessels. nephrons, which reach only a short
common sac called the urinary bladder. The excretory tubules carry and process a distance into the medulla. The remainder,
During urination, urine is expelled from the filtrate produced from the blood entering the juxtamedullary nephrons, extend
bladder through a tube called the urethra, the kidney. Nearly all of the fluid in the deep into the medulla. Juxtamedullary
which empties to the outside near the vagina filtrate is reabsorbed into the surround- nephrons are essential for production of
in females and through the penis in males. ing blood vessels and exits the kidney in urine that is hyperosmotic to body fluids,
Sphincter muscles near the junction of the the renal vein. The remaining fluid leaves a key adaptation for water conservation
urethra and bladder regulate urination. the excretory tubules as urine, is collected in mammals.
in the inner renal pelvis, and exits the
kidney via the ureter. Animation: Kidney Structure

As fluid passes from the tubules into the rectum, most sol- system also includes ducts and other structures that carry
utes are pumped back into the hemolymph; water reabsorp- urine from the tubules out of the kidney and, eventually,
tion by osmosis follows. The nitrogenous wastes—mainly the body.
insoluble uric acid—are eliminated as nearly dry matter along
with the feces. The insect excretory system is capable of con- Vertebrate kidneys are typically nonsegmented. However,
serving water very effectively, a key adaptation contributing hagfishes, which are jawless vertebrates (see Concept 34.2),
to the tremendous success of insects on land. have kidneys with segmentally arranged excretory tubules.
Because hagfishes and other vertebrates share a common
Kidneys chordate ancestor, it is possible that the excretory structures
of vertebrate ancestors were also segmented.
In vertebrates and some other chordates, a compact organ
called the kidney functions in both osmoregulation and We conclude this introduction to excretory systems with
excretion. Like the excretory organs of most animal phyla, an exploration of the anatomy of the mammalian kidney and
kidneys consist of tubules. The tubules of kidneys are associated structures (Figure 44.12). Familiarizing yourself
arranged in a highly organized manner and are closely asso- with the terms and diagrams in this figure will provide you
ciated with a network of capillaries. The vertebrate excretory with a solid foundation for learning about filtrate processing
in the kidney, the focus of the next section of this chapter.
984 Unit seven  Animal Form and Function

Nephron Organization

Afferent arteriole Glomerulus Each nephron consists of a single long tubule as well as a
from renal artery Bowman’s ball of capillaries called the glomerulus. The blind end of
capsule the tubule forms a cup-shaped swelling, called Bowman’s
capsule, which surrounds the glomerulus. Filtrate is formed
Proximal when blood pressure forces fluid from the blood in the glom-
tubule erulus into the lumen of Bowman’s capsule. Processing occurs
as the filtrate passes through three major regions of the neph-
Distal Peritubular ron: the proximal tubule, the loop of Henle (a hairpin
tubule capillaries turn with a descending limb and an ascending limb), and the
distal tubule. A collecting duct receives processed filtrate
Efferent from many nephrons and transports it to the renal pelvis.
arteriole from
glomerulus Each nephron is supplied with blood by an afferent arteriole,
an offshoot of the renal artery that branches and forms the
Collecting Branch of Descending capillaries of the glomerulus. The capillaries converge as they
duct renal vein limb leave the glomerulus, forming an efferent arteriole. Branches
Vasa of this vessel form the peritubular capillaries, which sur-
recta Loop of round the proximal and distal tubules. Other branches extend
Henle downward and form the vasa recta, hairpin-shaped capil-
Ascending laries that serve the renal medulla, including the long loop of
limb Henle of juxtamedullary nephrons.
▶ In this SEM of

densely packed
blood vessels from
a human kidney,
arterioles and
peritubular
capillaries appear
pink; the glomeruli
appear yellow.

200 μm

Concept Check 44.3 Concept  44.4

1. Compare and contrast the ways that metabolic waste The nephron is organized for
products enter the excretory systems of flatworms, stepwise processing of blood filtrate
earthworms, and insects.
In the human kidney, filtrate forms when fluid passes from
2. Where and how does filtrate originate in the vertebrate the bloodstream to the lumen of Bowman’s capsule. The
kidney, and by what two routes do the components of glomerular capillaries and specialized cells of Bowman’s
the filtrate exit the kidney? capsule retain blood cells and large molecules, such as
plasma proteins, but are permeable to water and small
3. WHAT IF? Kidney failure is often treated by hemodi- solutes. Thus, the filtrate produced in the capsule con-
alysis, in which blood diverted out of the body is filtered tains salts, glucose, amino acids, vitamins, nitrogenous
and then allowed to flow on one side of a semipermeable wastes, and other small molecules. Because such molecules
membrane. Fluid called dialysate flows in the opposite pass freely between glomerular capillaries and Bowman’s
direction on the other side of the membrane. In replacing
the reabsorption and secretion of solutes in a functional
kidney, the makeup of the starting dialysate is critical.
What initial solute composition would work well?
For suggested answers, see Appendix A.

chapter 44  Osmoregulation and Excretion 985

capsule, the concentrations of these substances in the secreted by the transport epithelium into the lumen of the
initial filtrate are the same as those in blood plasma. proximal tubule.

Under normal conditions, roughly 1,600 L of blood flows 2 Descending limb of the loop of Henle. Upon leav-
through a pair of human kidneys each day, yielding about ing the proximal tubule, filtrate enters the loop of Henle, which
180 L of initial filtrate. Of this, about 99% of the water and further reduces filtrate volume via distinct stages of water and
nearly all of the sugars, amino acids, vitamins, and other salt movement. In the first portion of the loop, the descending
organic nutrients are reabsorbed into the blood, leaving limb, numerous water channels formed by aquaporin pro-
only about 1.5 L of urine to be transported to the bladder. teins make the transport epithelium freely permeable to water.
In contrast, there are almost no channels for salt and other
From Blood Filtrate to Urine: A Closer Look small solutes, resulting in very low permeability for these
substances.
To explore how filtrate is processed into urine, we’ll follow
the filtrate along its path in the nephron (Figure 44.13). For water to move out of the tubule by osmosis, the inter-
Each circled number refers to the processing in transport stitial fluid bathing the tubule must be hyperosmotic to the
epithelia as the filtrate moves through the kidney cortex filtrate. This condition is met along the entire length of the
and medulla. descending limb because the osmolarity of the interstitial
fluid increases progressively from the cortex through the
1 Proximal tubule. Reabsorption in the proximal medulla. As a result, the filtrate loses water and increases in
tubule is critical for the recapture of ions, water, and valuable solute concentration all along its journey down the descend-
nutrients from the huge volume of initial filtrate. NaCl (salt) ing limb. The highest osmolarity (about 1,200 mOsm/L)
in the filtrate enters the cells of the transport epithelium by occurs at the elbow of the loop of Henle.
facilitated diffusion and cotransport mechanisms and then
is transferred to the interstitial fluid by active transport 3 Ascending limb of the loop of Henle. The filtrate
(see Concept 7.4). This transfer of positive charge out of the reaches the tip of the loop and then returns to the cortex in
tubule drives the passive transport of Cl-. the ascending limb. Unlike the descending limb, the ascend-
ing limb has a transport epithelium that lacks water chan-
As salt moves from the filtrate to the interstitial fluid, water nels. Consequently, the epithelial membrane that faces the
follows by osmosis, reducing filtrate volume considerably. The filtrate in the ascending limb is impermeable to water.
salt and water that exit the filtrate diffuse from the interstitial
fluid into the peritubular capillaries. Glucose, amino acids, The ascending limb has two specialized regions: a thin
potassium ions (K+), and other essential substances are also segment near the loop tip and a thick segment adjacent to
actively or passively transported from the filtrate to the inter- the distal tubule. As filtrate ascends in the thin segment,
stitial fluid and then into the peritubular capillaries. NaCl, which became highly concentrated in the descend-
ing limb, diffuses out of the permeable tubule into the
Processing of filtrate in the proximal tubule helps interstitial fluid. This movement of NaCl out of the tubule
maintain a relatively constant pH in body fluids. Cells of helps maintain the osmolarity of the interstitial fluid in the
the transport epithelium secrete H+ into the lumen of the medulla.
tubule but also synthesize and secrete ammonia, which
acts as a buffer to trap H+ in the form of ammonium ions In the thick segment of the ascending limb, the move-
(NH4+). The more acidic the filtrate is, the more ammonia ment of NaCl out of the filtrate continues. Here, however, the
the cells produce and secrete, and a mammal’s urine usu- epithelium actively transports NaCl into the interstitial fluid.
ally contains some ammonia from this source (even though As a result of losing salt but not water, the filtrate becomes
most nitrogenous waste is excreted as urea). The proximal progressively more dilute as it moves up to the cortex in the
tubules also reabsorb about 90% of the buffer bicarbonate ascending limb of the loop.
(HCO3-) from the filtrate, contributing further to pH
balance in body fluids. 4 Distal tubule. The distal tubule plays a key role in
regulating the K+ and NaCl concentration of body fluids.
As the filtrate passes through the proximal tubule, mate- This regulation involves variation in the amount of K+
rials to be excreted become concentrated. Many wastes secreted into the filtrate as well as the amount of NaCl reab-
leave the body fluids during the nonselective filtration sorbed from the filtrate. The distal tubule also contributes
process and remain in the filtrate while water and salts to pH regulation by the controlled secretion of H+ and reab-
are reabsorbed. Urea, for example, is reabsorbed at a much sorption of HCO3-.
lower rate than are salt and water. In addition, some mate-
rials are actively secreted into the filtrate from surround- 5 Collecting duct. The collecting duct processes the
ing tissues. For example, drugs and toxins that have been filtrate into urine, which it carries to the renal pelvis (see
processed in the liver pass from the peritubular capillaries Figure 44.12). As filtrate passes along the transport epithe-
into the interstitial fluid. These molecules are then actively lium of the collecting duct, hormonal control of permeabil-
ity and transport determines the extent to which the urine
986 Unit seven  Animal Form and Function becomes concentrated.

Figure 44.13  The nephron and collecting duct: regional functions of the transport
epithelium. The numbered regions in this diagram are keyed to the circled numbers in the text
discussion of kidney function.

1 Proximal tubule 4 Distal tubule
NaCl H2O HCO3–
NaCl Nutrients

HCO3– H2O K+

H+ NH3 K+ H+
Interstitial
CORTEX fluid

Filtrate 2 Descending limb 3 Thick segment
of loop of of ascending
H2O Henle limb
Salts (NaCl and others) H2O NaCl
HCO3–
H+ OUTER 3 Thin segment NaCl
Urea MEDULLA of ascending 5 Collecting
Glucose, amino acids limb
Some drugs NaCl duct

Key Urea
H2O
Active transport
Passive transport INNER
MEDULLA
? m Soaminetacienllns olirnminagl tubules in the kidney
cell volume by

synthesizing organic solutes. Where in

the kidney would you expect to find

these cells? Explain.

Animation: Nephron Function

When the kidneys are conserving water, aquaporin chan- the collecting duct epithelium is controlled by hormones that
nels in the collecting duct allow water molecules to cross regulate blood pressure, volume, and osmolarity.
the epithelium. At the same time, the epithelium remains
impermeable to salt and, in the renal cortex, to urea. As the Solute Gradients and Water Conservation
collecting duct traverses the gradient of osmolarity in the
kidney, the filtrate becomes increasingly concentrated, los- The ability of the mammalian kidney to conserve water is a
ing more and more water by osmosis to the hyperosmotic key adaptation for terrestrial habitats. In humans, the osmo-
interstitial fluid. In the inner medulla, the duct becomes larity of blood is about 300 mOsm/L, but the kidney can
permeable to urea. Because of the high urea concentration excrete urine up to four times as concentrated—about 1,200
in the filtrate at this point, some urea diffuses out of the mOsm/L. Some mammals can do even better: Australian hop-
duct and into the interstitial fluid. Along with NaCl, this ping mice, small marsupials that live in dry desert regions,
urea contributes to the high osmolarity of the interstitial can produce urine with an osmolarity of 9,300 mOsm/L,
fluid in the medulla. The net result is urine that is hyperos- 25 times as concentrated as the animal’s blood.
motic to the general body fluids.
In a mammalian kidney, the production of hyperosmotic
When producing dilute rather than concentrated urine, urine is possible only because considerable energy is expended
the collecting duct actively absorbs salts without allowing for the active transport of solutes against concentration gra-
water to follow by osmosis. At these times, the epithelium dients. The nephrons—particularly the loops of Henle—can
lacks aquaporin channels, and NaCl is actively transported be thought of as energy-consuming machines that produce
out of filtrate. As we’ll see, the presence of water channels in an osmolarity gradient suitable for extracting water from

chapter 44  Osmoregulation and Excretion 987

the filtrate in the collecting duct. The primary solutes affect- increasing the osmolarity of the filtrate. Diffusion of salt out
ing osmolarity are NaCl, which is concentrated in the renal of the tubule is maximal as the filtrate rounds the curve and
medulla by the loop of Henle, and urea, which passes across enters the ascending limb, which is permeable to salt but not to
the epithelium of the collecting duct in the inner medulla. water. NaCl diffusing from the ascending limb helps maintain
a high osmolarity in the interstitial fluid of the renal medulla.
Concentrating Urine in the Mammalian Kidney
The loop of Henle and surrounding capillaries act as a type
To better understand the physiology of the mammalian of countercurrent system to generate the steep osmotic gradi-
kidney as a water-conserving organ, let’s retrace the flow of ent between the medulla and cortex. Recall that some endo-
filtrate through the excretory tubule. This time, let’s focus therms have a countercurrent heat exchanger that reduces
on how juxtamedullary nephrons maintain an osmolarity heat loss and that countercurrent gas exchange in fish gills
gradient in the tissues that surround the loop of Henle and maximizes oxygen absorption (see Figures 40.13 and 42.21).
how they use that gradient to excrete hyperosmotic urine In those cases, the countercurrent mechanisms involve passive
(Figure 44.14). Filtrate passing from Bowman’s capsule to movement along either an oxygen concentration gradient or
the proximal tubule has about the same osmolarity as blood. a heat gradient. In contrast, the countercurrent system of the
A large amount of water and salt is reabsorbed from the filtrate loop of Henle involves active transport and thus an expendi-
as it flows through the proximal tubule in the renal cortex. ture of energy. The active transport of NaCl from the filtrate in
As a result, the filtrate’s volume decreases substantially, but the upper part of the ascending limb of the loop maintains a
its osmolarity remains about the same. high salt concentration in the interior of the kidney, enabling
the kidney to form concentrated urine. Such countercurrent
As the filtrate flows from cortex to medulla in the descend- systems, which expend energy to create concentration gradi-
ing limb of the loop of Henle, water leaves the tubule by ents, are called countercurrent multiplier systems.
osmosis. Solutes, including NaCl, become more concentrated,

300 300 100 Osmolarity of
300 100 interstitial
fluid
Figure 44.14  How the human CORTEX H2O NaCl H2O (mOsm/L)
kidney concentrates urine. Two H2O
solutes contribute to the osmolarity of the H2O 400 200 H2O 300 300
interstitial fluid: NaCl (used as shorthand H2O
here to refer collectively to Na+ and Cl-) 400 400
and urea. The loop of Henle maintains
the interstitial gradient of NaCl, which NaCl NaCl
increases continuously in concentration
from the cortex to the inner medulla. OUTER 600 400 H2O 600 600
Urea diffuses into the interstitial fluid MEDULLA NaCl 900
of the medulla from the collecting duct H2O
(although most of the urea in the filtrate 900 700 Urea 1,200 1,200
remains in the collecting duct and is NaCl
excreted). The filtrate makes three trips Key INNER H2O
between the cortex and medulla: first MEDULLA Urea
down, then up, and then down again in Active
the collecting duct. As the filtrate flows in transport 1,200
the collecting duct past interstitial fluid of Passive
increasing osmolarity, more water moves transport
out of the duct by osmosis. The loss of
water concentrates the solutes, including
urea, that will be excreted in the urine.

WHAT IF? The drug furosemide blocks the cotransporters for Na+ and Cl - in the ascending Figure Walkthrough
limb of the loop of Henle. What effect would you expect this drug to have on urine volume?

988 Unit seven  Animal Form and Function

What prevents the capillaries of the vasa recta from dis- vertebrates across environments reveals adaptive variations in
sipating the gradient by carrying away the high concentra- nephron structure and function. In the case of mammals, for
tion of NaCl in the medulla’s interstitial fluid? As shown example, the presence of juxtamedullary nephrons is a key ad-
in Figure 44.12, the descending and ascending vessels of aptation that enables these terrestrial animals to shed salts and
the vasa recta carry blood in opposite directions through nitrogenous wastes without squandering water. Differences
the kidney’s osmolarity gradient. As the descending vessel among species in the length of the loop of Henle in the juxta-
conveys blood toward the inner medulla, water is lost from medullary nephrons and in the relative numbers of juxtamed-
the blood and NaCl is gained by diffusion. These net fluxes ullary and cortical nephrons help to fine-tune osmoregulation
are reversed as blood flows back toward the cortex in the to particular habitats.
ascending vessel of the vasa recta, with water reentering the
blood and salt diffusing out. Thus, the vasa recta can supply Mammals
the kidney with nutrients and other important substances
carried by the blood without interfering with the osmolarity Mammals that excrete the most hyperosmotic urine, such as
gradient in the inner and outer medulla. Australian hopping mice, North American kangaroo rats, and
other desert mammals, have many juxtamedullary nephrons
The countercurrent-like characteristics of the loop of with loops of Henle that extend deep into the medulla. Long
Henle and the vasa recta help to generate the steep osmotic loops maintain steep osmotic gradients in the kidney, result-
gradient between the medulla and cortex. However, diffusion ing in urine becoming very concentrated as it passes from
will eventually eliminate any osmotic gradient within animal cortex to medulla in the collecting ducts.
tissue unless energy is expended to maintain the gradient. In
the kidney, this expenditure largely occurs in the thick seg- In contrast, beavers, muskrats, and other aquatic mam-
ment of the ascending limb of the loop of Henle, where NaCl mals that spend much of their time in fresh water and rarely
is actively transported out of the tubule. Even with the ben- face problems of dehydration have mostly cortical neph-
efits of countercurrent exchange, this process—along with rons, resulting in a much lower ability to concentrate urine.
other renal active transport systems—consumes considerable Terrestrial mammals living in moist conditions have loops
ATP. Thus, for its size, the kidney has one of the highest meta- of Henle of intermediate length and the capacity to produce
bolic rates of any organ. urine intermediate in concentration to that produced by
freshwater and desert mammals.
As a result of active transport of NaCl out of the thick seg-
ment of the ascending limb, the filtrate is actually hypoos- Case Study: Kidney Function
motic to body fluids by the time it reaches the distal tubule. in the Vampire Bat
Next, the filtrate descends again toward the medulla, this time
in the collecting duct, which is permeable to water but not The South American vampire bat shown in Figure 44.15
to salt. Therefore, osmosis extracts water from the filtrate as illustrates the versatility of the mammalian kidney. This spe-
it passes from cortex to medulla and encounters interstitial cies feeds at night on the blood of large birds and mammals.
fluid of increasing osmolarity. This process concentrates salt, The bat uses its sharp teeth to make a small incision in the
urea, and other solutes in the filtrate. Some urea passes out of prey’s skin and then laps up blood from the wound (the prey
the lower portion of the collecting duct and contributes to the is typically not seriously harmed). Anticoagulants in the bat’s
high interstitial osmolarity of the inner medulla. (This urea saliva prevent the blood from clotting.
is recycled by diffusion into the loop of Henle, but continual
leakage from the collecting duct maintains a high interstitial A vampire bat may search for hours and fly long distances
urea concentration.) When the kidney concentrates urine to locate a suitable victim. When it does find prey, it benefits
maximally, the urine reaches 1,200 mOsm/L, the osmolarity of from consuming as much blood as possible. Often drinking
the interstitial fluid in the inner medulla. Although isoosmotic more than half its body mass, the bat is at risk of becoming too
to the inner medulla’s interstitial fluid, the urine is hyperosmotic
to blood and interstitial fluid elsewhere in the body. This high Figure 44.15  A vampire
osmolarity allows the solutes remaining in the urine to be bat (Desmodus rotundus),
excreted from the body with minimal water loss. a mammal with unique
excretory challenges.
Adaptations of the Vertebrate Kidney
to Diverse Environments

Evolution Vertebrates occupy habitats ranging from rain
forests to deserts and from some of the saltiest bodies of water
to the nearly pure waters of high mountain lakes. Comparing

chapter 44  Osmoregulation and Excretion 989

heavy to fly. As the bat feeds, however, its kidneys excrete large urine and feces leave the body conserves fluid by reabsorb-
volumes of dilute urine, up to 24% of body mass per hour. ing water from these wastes. Like birds, most other reptiles
Having lost enough weight to take off, the bat can fly back to excrete their nitrogenous wastes as uric acid.
its roost in a cave or hollow tree, where it spends the day.
Freshwater Fishes and Amphibians
In the roost, the vampire bat faces a different regulatory prob-
lem. Most of the nutrition it derives from blood comes in the Hyperosmotic to their surroundings, freshwater fishes pro-
form of protein. Digesting proteins generates large quantities of duce large volumes of very dilute urine. Their kidneys, which
urea, but roosting bats lack access to the drinking water neces- are packed with cortical nephrons, produce filtrate at a high
sary to dilute it. Instead, their kidneys shift to producing small rate. Salt conservation relies on the reabsorption of ions from
quantities of highly concentrated urine (up to 4,600 mOsm/L), the filtrate in the distal tubules.
an adjustment that disposes of the urea load while conserving
as much water as possible. The vampire bat’s ability to alternate Amphibian kidneys function much like those of freshwa-
rapidly between producing large amounts of dilute urine and ter fishes. When frogs are in fresh water, their kidneys excrete
small amounts of very hyperosmotic urine is an essential part dilute urine while their skin accumulates certain salts from
of its adaptation to an unusual food source. the water by active transport. On land, where dehydration is
the most pressing problem of osmoregulation, frogs conserve
Birds and Other Reptiles body fluid by reabsorbing water across the epithelium of the
urinary bladder.
Most birds, including the albatross (see Figure 44.1) and
the ostrich (Figure 44.16), live in environments that are Marine Bony Fishes
dehydrating. Like mammals but no other species, birds
have kidneys with juxtamedullary nephrons. However, the Compared with freshwater fishes, marine fishes have fewer
nephrons of birds have loops of Henle that extend less far and smaller nephrons, and their nephrons lack a distal
into the medulla than those of mammals. Thus, bird kidneys tubule. In addition, their kidneys have small glomeruli or lack
cannot concentrate urine to the high osmolarities achieved glomeruli entirely. In keeping with these features, filtration
by mammalian kidneys. Although birds can produce hyper- rates are low and very little urine is excreted.
osmotic urine, their main water conservation adaptation is
having uric acid as the nitrogenous waste molecule. The main function of kidneys in marine bony fishes is to
get rid of divalent ions (those with a charge of 2+ or 2-) such
The kidneys of other reptiles have only cortical nephrons as calcium (Ca2+), magnesium (Mg2+), and sulfate (SO42-).
and produce urine that is isoosmotic or hypoosmotic to body Marine fishes take in divalent ions by incessantly drinking
fluids. However, the epithelium of the cloaca from which seawater. They rid themselves of these ions by secreting them
into the proximal tubules of the nephrons and excreting
Figure 44.16  An ostrich (Struthio camelus), them in urine. Osmoregulation in marine bony fishes also
an animal well adapted to its dry environment. relies on specialized chloride cells in the gills. By establishing
ion gradients that enable secretion of salt (NaCl) into sea-
990 Unit seven  Animal Form and Function water, the chloride cells maintain proper levels of monova-
lent ions (charge of 1+ or 1-) such as Na+ and Cl-.

The generation of ion gradients and the movement of ions
across membranes are central to salt and water balance in
marine bony fishes. These events, however, are by no means
unique to these organisms nor to homeostasis. As illustrated
by the examples in Figure 44.17, osmoregulation by chloride
cells is but one of many diverse physiological processes that
are driven by the movement of ions across a membrane.

Concept Check 44.4

1. What do the number and length of nephrons in a fish’s
kidney indicate about the fish’s habitat? How do they
correlate with urine production?

2. Many medications make the epithelium of the collecting
duct less permeable to water. How would taking such a
medication affect kidney output?

3. WHAT IF? If blood pressure in the afferent arteriole
leading to a glomerulus decreased, how would the rate
of blood filtration within Bowman’s capsule be affected?
Explain.

For suggested answers, see Appendix A.

Figure 44.17 Make Connections Channel Channel
open closed
Ion Movement and Gradients
Na+
The transport of ions across the plasma membrane of a
cell is a fundamental activity of all animals, and indeed
of all living things. By generating ion gradients, ion
transport provides the potential energy that powers
processes ranging from an organism’s regulation of
salts and gases in internal fluids to its perception of
and locomotion through its environment.

SALT WATER Information Processing Na+
Na+ Cl– NEURON

CHLORIDE In neurons, transmission of information as nerve impulses is
K+ CELL made possible by the opening and closing of channels selective
for sodium or other ions. These signals enable nervous systems to
Osmoregulation receive and process input and to direct appropriate output, such
as this leap of a frog capturing prey. (See Concept 48.3 and
Na+ Concept 50.5.)
BLOOD
In marine bony fishes, ion K+
gradients drive secretion of salt

(NaCl), a process essential to avoid
dehydration. Within gills, the pumps,

cotransporters, and channels of specialized chloride cells function
together to drive salt from the blood across the gill epithelium and
into the surrounding salt water. (See Figure 44.4.)

Filament of
flagellum

Flagellar
motor

H2O H2O Hook
H+ H2O H+

K+ Locomotion

K+ A gradient of H+ ions powers the bacterial flagellum. An electron
transport chain generates this gradient, establishing a higher
H+ concentration of H+ outside the bacterial cell. Protons reentering
the cell provide a force that causes the flagellar motor to rotate.
H2O H2O The rotating motor turns the curved hook, causing the attached
Guard cells filament to propel the cell. (See Concept 9.4 and Figure 27.7)

Gas Exchange MAKE CONNECTIONS Explain why the set of forces driving ion
movement across the plasma membrane of a cell is described as an
Ion gradients provide the basis for the opening of plant stomata electrochemical (electrical and chemical) gradient (see Concept 7.4).
by surrounding guard cells. Active transport of H+ out of a guard
cell generates a voltage (membrane potential) that drives inward BioFlix® Animation: Membrane Transport
movement of K+ ions. This uptake of K+ by guard cells triggers
an osmotic influx of water that changes cell shape, bowing
the guard cells outward and thereby opening the stoma. (See
Concept 36.4.)

chapter 44  Osmoregulation and Excretion 991

Concept  44.5 Figure 44.18  Control of collecting Collecting
duct permeability by antidiuretic duct
Hormonal circuits link kidney hormone (ADH).
function, water balance,
and blood pressure ADH LUMEN
receptor
In mammals, both the volume and osmolarity of urine are COLLECTING 1 ADH binds
adjusted according to an animal’s water and salt balance and ADH DUCT CELL to membrane
its rate of urea production. In situations of high salt intake receptor.
and low water availability, a mammal can excrete urea and
salt in small volumes of hyperosmotic urine with minimal cAMP Second 2 Receptor
water loss. If salt is scarce and fluid intake is high, the kidney messenger triggers signal
can instead eliminate the excess water with little salt loss transduction.
by producing large volumes of hypoosmotic urine. At such
times, the urine can be as dilute as 70 mOsm/L, less than Protein 3 Vesicles
one-fourth the osmolarity of human blood. kinase A with aquaporin
Storage water channels
How are urine volume and osmolarity regulated so effec- vesicle are inserted
tively? As we’ll explore in this final portion of the chapter, into membrane
two major control circuits that respond to different stimuli Aquaporin Exocytosis lining lumen of
together restore and maintain normal water and salt balance. water H2O collecting duct.
channel 4 Aquaporin
Homeostatic Regulation of the Kidney channels
H2O enhance
A combination of nervous and hormonal controls manages reabsorption
the osmoregulatory function of the mammalian kidney. of water from
Through their effects on the amount and osmolarity of urine, collecting duct
these controls contribute to homeostasis for both blood pres- into interstitial
sure and blood volume. fluid.

Antidiuretic Hormone Figure 44.19  Regulation of fluid retention in the kidney. Osmoreceptors in the
hypothalamus monitor blood osmolarity via its effect on the net diffusion of water into or out
One key hormone in of the kidney of the receptor cells. When blood osmolarity increases, signals from the osmoreceptors trigger
is antidiuretic hormone (ADH), a release of ADH from the posterior pituitary and generate thirst. Water reabsorption in the
also called vasopressin. ADH molecules collecting duct and water intake restore normal blood osmolarity, inhibiting further ADH secretion.
released from the posterior pituitary bind
to and activate membrane receptors on Osmoreceptors Hypothalamus Specific neurons
the surface of collecting duct cells. The in hypothalamus of hypothalamus
activated receptors initiate a signal trans- trigger release of Posterior generate thirst.
duction cascade that directs insertion of ADH from pituitary Distal
aquaporin proteins into the membrane posterior tubule
lining the collecting duct (Figure 44.18). pituitary.
More aquaporin channels result in more
water recapture, reducing urine volume. Blood osmolarity ADH Drinking water
(A high level of urine production is increases Collecting reduces blood
called diuresis; ADH is therefore called duct osmolarity.
antidiuretic hormone.) (such as after H2O reabsorption
sweating profusely). reduces blood
To understand the regulatory circuitry osmolarity.
based on ADH, let’s consider first what
occurs when blood osmolarity rises, such NORMAL Animation: Control of
as after eating salty food or losing water BLOOD OSMOLARITY Water Reabsorption
through sweating (Figure 44.19). When
osmolarity rises above the normal range (285–295 mOsm/L)
(285–295 mOsm/L), osmoreceptor cells

992 Unit seven  Animal Form and Function

in the hypothalamus trigger increased release of ADH from Figure 44.20
the posterior pituitary. The resulting increase in water reab-
sorption in the collecting duct concentrates urine, reduces Inquiry  Can aquaporin mutations cause diabetes?
urine volume, and lowers blood osmolarity back toward the
set point. As the osmolarity of the blood falls, a negative- Experiment  Researchers studied a diabetes insipidus patient with
feedback mechanism reduces the activity of osmoreceptor a normal ADH receptor gene but two mutant alleles (A and B) of
cells in the hypothalamus, and ADH secretion is reduced. the aquaporin-2 gene. The resulting changes are shown below in
an alignment of protein sequences that includes other species.
What happens if, instead of ingesting salt or sweating pro-
fusely, you drink a large amount of water? Blood osmolarity Amino Acids Amino Acids
falls below the set point, causing a drop in ADH secretion to Source of Aquaporin-2 183–191* in 212–220* in
a very low level. The resulting decrease in permeability of the Gene Sequence Encoded Protein Encoded Protein
collecting ducts reduces water reabsorption, resulting in dis-
charge of large volumes of dilute urine. Frog (Xenopus laevis) MNPARSFAP GIFASLIYN

Contrary to common belief, caffeinated drinks increase Lizard (Anolis carolinensis) MNPARSFGP AVVASLLYN
urine production to no greater degree than water of compara-
ble volume: Numerous studies of coffee and tea drinkers have Chicken (Gallus gallus) MNPARSFAP AAAASIIYN
found no diuretic effect for caffeine.
Human (Homo sapiens) MNPARSLAP AILGSLLYN
Blood osmolarity, ADH release, and water reabsorption
in the kidney are normally linked in a feedback circuit that Conserved residues MNPARSxxP xxxxSxxYN
contributes to homeostasis. Anything that disrupts this cir-
cuit can interfere with water balance. For example, alcohol Patient’s gene: allele A MNPACSLAP AILGSLLYN
inhibits ADH release, leading to excessive urinary water loss
and dehydration (which may cause some of the symptoms Patient’s gene: allele B MNPARSLAP AILGPLLYN
of a hangover).
*The numbering is based on the human aquaporin-2 protein sequence.
Mutations that prevent ADH production or that inactivate
the ADH receptor gene disrupt homeostasis by blocking the Each mutation changed the protein sequence at a highly conserved
insertion of additional aquaporin channels in the collect- position. To test the hypothesis that the changes affect function, re-
ing duct membrane. The resulting disorder can cause severe searchers used frog oocytes, cells that will express foreign messenger
dehydration and solute imbalance due to production of copi- RNA and can be readily collected from adult female frogs.
ous dilute urine. These symptoms give the disorder its name:
diabetes insipidus (from the Greek for “to pass through” and 1 Messenger RNA Wild-type Allele A Allele B H2O
“having no flavor”). Could mutations in an aquaporin gene transcribed from 10-mOsm (control)
have a similar effect? Figure 44.20 describes an experimental wild-type and solution
approach that addressed this question. mutant aquaporin
genes is injected
The Renin-Angiotensin-Aldosterone System into frog oocytes,
where it directs the
The release of ADH is a response to an increase in blood synthesis of
osmolarity, as when the body is dehydrated from excessive aquaporin proteins.
water loss or inadequate water intake. However, an exces-
sive loss of both salt and body fluids—caused, for example, 2 The oocytes are Oocyte
by a major wound or severe diarrhea—will reduce blood transferred from a
volume without increasing osmolarity. Given that this will 200-mOsm to a
not affect ADH release, how does the body respond? It turns 10-mOsm solution.
out that an endocrine circuit called the renin-angiotensin- The rate of oocyte
aldosterone system (RAAS) also regulates kidney function. swelling is measured
The RAAS responds to the drop in blood volume and pres- as an indicator of
sure by increasing water and Na+ reabsorption. water permeability.

The RAAS involves the juxtaglomerular apparatus Results Rate of Swelling (µm/sec)
(JGA), a specialized tissue consisting of cells of and around Source of Injected mRNA 196
the afferent arteriole, which supplies blood to the glomerulus. Human wild type  17
When blood pressure or volume drops in the afferent arteriole Patient’s allele A  18
(for instance, as a result of dehydration), the JGA releases the Patient’s allele B  20
None (H2O control)

Conclusion  Because each mutation renders aquaporin inactive as a
water channel, researchers concluded that these mutations cause the
disorder common to the patients.

Data from  P. M. Deen et al., Requirement of human renal water channel aquaporin-2
for vasopressin-dependent concentration of urine, Science 264:92–95 (1994).

WHAT IF? If you measured ADH levels in patients with ADH receptor
mutations and in patients with aquaporin mutations, what would you expect

to find, compared with wild-type subjects?

chapter 44  Osmoregulation and Excretion 993

Figure 44.21  Regulation of blood More Na+ and H2O are NORMAL
volume and blood pressure by the reabsorbed in distal tubules, BLOOD PRESSURE
renin-angiotensin-aldosterone system increasing blood volume.
(RAAS). AND VOLUME
Aldosterone
VISUAL SKILLS Label each arrow that
represents the secretion of a hormone. Blood pressure or
blood volume drops
Adrenal gland Arterioles constrict, (for example, due to
increasing blood dehydration or blood loss).
pressure.

Angiotensin II Distal
tubule

ACE JGA Sensors in
Angiotensin I releases JGA detect
renin. decrease in
Angiotensinogen Renin pressure or
volume.

Liver Juxtaglomerular
apparatus (JGA)

enzyme renin. Renin initiates a sequence of steps that cleave a Another hormone, atrial natriuretic peptide (ANP),
plasma protein called angiotensinogen, ultimately yielding a opposes the RAAS. The walls of the atria of the heart release
peptide called angiotensin II (Figure 44.21). ANP in response to an increase in blood volume and pressure.
ANP inhibits the release of renin from the JGA, inhibits NaCl
Functioning as a hormone, angiotensin II triggers vasocon- reabsorption by the collecting ducts, and reduces aldosterone
striction, increasing blood pressure and decreasing blood flow release from the adrenal glands. These actions lower blood
to capillaries in the kidney (and elsewhere). Angiotensin II volume and pressure. Thus, ADH, the RAAS, and ANP provide
also stimulates the adrenal glands to release a hormone called an elaborate system of checks and balances that regulate the
aldosterone. Aldosterone causes the nephrons’ distal tubules kidney’s ability to control blood osmolarity, salt concentra-
and collecting duct to reabsorb more Na+ and water, increas- tion, volume, and pressure.
ing blood volume and pressure.
Thirst plays an essential role in the control of water and
Because angiotensin II results in increased blood pressure, salt balance. Recently, researchers have identified neurons in
drugs that block angiotensin II production are widely used the hypothalamus dedicated to regulating thirst. Stimulating
to treat hypertension (chronic high blood pressure). Many of one set of neurons in mice causes intense drinking behavior,
these drugs are specific inhibitors of angiotensin converting even if the animal is fully hydrated. Stimulating a second
enzyme (ACE), which catalyzes one of the steps in the pro- set causes an immediate halt in water consumption, even in
duction of angiotensin II. dehydrated animals. Follow-up studies are focused on iden-
tifying the cellular and molecular pathways linking these
The RAAS operates as a feedback circuit. A drop in blood neurons to the behavioral responses.
pressure and blood volume triggers renin release. The result-
ing production of angiotensin II and release of aldosterone Concept Check 44.5
cause a rise in blood pressure and volume, reducing the
release of renin from the JGA. 1. How does alcohol affect regulation of water balance
in the body?
Coordinated Regulation of Salt
and Water Balance 2. Why could it be dangerous to drink a very large amount
of water in a short period of time?
Both ADH and RAAS increase water reabsorption in the
kidney. However, whereas ADH alone would lower blood 3. WHAT IF? Conn’s syndrome is a condition caused by
Na+ concentration via water reabsorption in the kidney, the tumors of the adrenal cortex that secrete high amounts
RAAS helps maintain body fluid osmolarity at the set point of aldosterone in an unregulated manner. What would
by stimulating Na+ reabsorption. you expect to be the major symptom of this disorder?

For suggested answers, see Appendix A.

994 Unit seven  Animal Form and Function

44 Chapter Review Go to MasteringBiology™ for Videos, Animations, Vocab Self-Quiz,
Practice Tests, and more in the Study Area.

Summary of Key Concepts VOCAB Concept  44.2
SELF-QUIZ
Concept  44.1 goo.gl/6u55ks An animal’s nitrogenous wastes reflect
its phylogeny and habitat (pp. 980–981)
Osmoregulation balances the uptake
and loss of water and solutes Protein and nucleic acid metabolism generates ammonia. Most
(pp. 976–980) aquatic animals excrete ammonia. Mammals and most adult
amphibians convert ammonia to the less toxic urea, which is
Animal Inflow/Outflow Urine excreted with a minimal loss of water. Insects and many reptiles,
Freshwater Large volume including birds, convert ammonia to uric acid, a mostly insol-
fish. Lives in Does not drink water of urine uble waste excreted in a paste-like urine.
water less Urine is less
concentrated Salt in H2O in concentrated The kind of nitrogenous waste excreted depends on an animal’s
than body (active trans- than body habitat, whereas the amount excreted is coupled to the animal’s
fluids; fish port by gills) fluids energy budget and dietary protein intake.
tends to gain
water, lose salt DRAW IT Construct a table summarizing the three major types of
nitrogenous wastes and their relative toxicity, energy cost to produce,
and associated water loss during excretion.

Marine bony Salt out H2O out Small volume Concept  44.3
fish. Lives in Drinks water of urine
water more Urine is Diverse excretory systems are variations
concentrated Salt in H2O out slightly less on a tubular theme (pp. 982–985)
than body concentrated
fluids; fish Salt out (active than body Most excretory systems carry out filtration, reabsorption,
tends to lose transport by gills) fluids secretion, and excretion. Invertebrate excretory systems
water, gain salt include the protonephridia of flatworms, the metane-
phridia of earthworms, and the Malpighian tubules of
Terrestrial Drinks water Moderate insects. Kidneys function in both excretion and osmoregulation
vertebrate. Salt in volume in vertebrates.
Terrestrial (by mouth) of urine
environment; Urine is Excretory tubules (consisting of nephrons and collecting
tends to lose H2O and more ducts) and blood vessels pack the mammalian kidney. Blood
body water salt out concentrated pressure forces fluid from blood in the glomerulus into
to air than body the lumen of Bowman’s capsule. Following reabsorption
fluids and secretion, filtrate flows into a collecting duct.
The ureter conveys urine from the renal pelvis to
the urinary bladder.

? What is the function of the filtration step in excretory systems?

Concept  44.4

The nephron is organized for stepwise processing
of blood filtrate (pp. 985–991)

Cells balance water gain and loss through osmoregulation, Within the nephron, selective secretion and reabsorption in
a process based on the controlled movement of solutes between the proximal tubule alter filtrate volume and composition.
internal fluids and the external environment and on the move- The descending limb of the loop of Henle is permeable to water
ment of water, which follows by osmosis. but not salt; water moves by osmosis into the interstitial fluid.
The ascending limb is permeable to salt but not water; salt leaves
Osmoconformers are isoosmotic with their marine envi- by diffusion and by active transport. The distal tubule and
ronment and do not regulate their osmolarity. In contrast, collecting duct regulate K+ and NaCl levels in body fluids.
osmoregulators control water uptake and loss in a hypoos-
motic or hyperosmotic environment, respectively. Water- In mammals, a countercurrent multiplier system involving
conserving excretory organs help terrestrial animals avoid the loop of Henle maintains the gradient of salt concentration in
desiccation, which can be life-threatening. Animals that live the kidney interior. Urea exiting the collecting duct contributes
in temporary waters may enter a dormant state called to the osmotic gradient of the kidney.
anhydrobiosis when their habitats dry up.
Natural selection has shaped the form and function of neph-
Transport epithelia contain specialized epithelial cells that rons in various vertebrates to the osmoregulatory challenges
control the solute movements required for waste disposal and of the animals’ habitats. For example, desert mammals,
osmoregulation. which excrete the most hyperosmotic urine, have loops of
Henle that extend deep into the renal medulla, whereas
mammals in moist habitats have shorter loops and excrete
more dilute urine.

? Under what environmental conditions does water move into a cell by ? How do cortical and juxtamedullary nephrons differ with respect to
osmosis? reabsorbing nutrients and concentrating urine?

chapter 44  Osmoregulation and Excretion 995

Concept  44.5 Level 3: Synthesis/Evaluation

Hormonal circuits link kidney function, water 7. INTERPRET THE DATA  Use the data below to draw four pie
balance, and blood pressure (pp. 992–994) charts for water gain and loss in a kangaroo rat and a human.

The posterior pituitary gland releases antidiuretic hormone Ingested in food Kangaroo Rat Human
(ADH) when blood osmolarity rises above a set point, such as Ingested in liquid Water Gain (mL)
when water intake is inadequate. ADH increases the permeability Derived from     750
to water of the collecting ducts by increasing the number of metabolism 0.2 1,500
epithelial aquaporin channels. 0     250
Urine 1.8
When blood pressure or blood volume in the afferent arteriole Feces 1,500
drops, the juxtaglomerular apparatus releases renin. Evaporation Water Loss (mL)     100
Angiotensin II formed in response to renin constricts arterioles and 0.45     900
triggers release of the hormone aldosterone, raising blood pressure 0.09
and reducing the release of renin. This renin-angiotensin- 1.46
aldosterone system has functions that overlap with those of
ADH and are opposed by atrial natriuretic peptide.

? Why can only some patients with diabetes insipidus be treated
effectively with ADH?
Which routes of water gain and loss make up a much larger
Test Your Understanding share of the total in a kangaroo rat than in a human?
8. EVOLUTION CONNECTION  Merriam’s kangaroo rats
Level 1: Knowledge/Comprehension (Dipodomys merriami) live in North American habitats
ranging from moist, cool woodlands to hot deserts. Based
1. Unlike an earthworm’s metanephridia, on the hypothesis that there are adaptive differences in
a mammalian nephron water conservation between D. merriami populations,
(A) is intimately associated with a capillary predict how the rates of evaporative water loss would differ
network. PRACTICE for populations that live in moist versus dry environments.
TEST Propose a test of your prediction, using a humidity sensor to
goo.gl/CUYGKD detect evaporative water loss by kangaroo rats.
(B) functions in both osmoregulation and 9. SCIENTIFIC INQUIRY  You are exploring kidney function in
excretion. kangaroo rats. You measure urine volume and osmolarity, as well
(C) receives filtrate from blood instead of coelomic fluid. as the amount of chloride (Cl-) and urea in the urine. If the water
(D) has a transport epithelium. source provided to the animals were switched from tap water to
a 2% NaCl solution, indicate what change in urine osmolarity
2. Which process in the nephron is least selective? you would expect. How would you determine if this change was
(A) filtration (C) active transport more likely due to a change in the excretion of Cl- or urea?
(B) reabsorption (D) secretion 10. WRITE ABOUT A THEME: Organization  In a short essay
(100–150 words), compare how membrane structures in the
3. Which of the following animals generally has the lowest loop of Henle and collecting duct of the mammalian kidney
volume of urine production? enable water to be recovered from filtrate in the process of
(A) vampire bat osmoregulation.
(B) salmon in fresh water
(C) marine bony fish
(D) freshwater flatworm

Level 2: Application/Analysis 11. SYNTHESIZE YOUR KNOWLEDGE

4. The high osmolarity of the renal medulla is maintained by all The marine iguana
of the following except (Amblyrhynchus cris-
(A) active transport of salt from the upper region of the tatus), which spends
ascending limb. long periods under
(B) the spatial arrangement of juxtamedullary nephrons. water feeding on sea-
(C) diffusion of urea from the collecting duct. weed, relies on both
(D) diffusion of salt from the descending limb of the loop salt glands and kid-
of Henle. neys for homeostasis
of its internal fluids.
5. In which of the following species should natural selection favor Describe how these or-
the highest proportion of juxtamedullary nephrons? gans together meet the
(A) a river otter particular osmoregula-
(B) a mouse species living in a temperate broadleaf forest tory challenges of this
(C) a mouse species living in a desert animal’s environment.
(D) a beaver
For selected answers, see Appendix A.
6. African lungfish, which are often found in small stagnant pools
of fresh water, produce urea as a nitrogenous waste. What is the For additional practice questions, check out the Dynamic Study
advantage of this adaptation? Modules in MasteringBiology. You can use them to study on
(A) Urea takes less energy to synthesize than ammonia. your smartphone, tablet, or computer anytime, anywhere!
(B) Small stagnant pools do not provide enough water to dilute
ammonia, which is toxic.
(C) Urea forms an insoluble precipitate.
(D) Urea makes lungfish tissue hypoosmotic to the pool.

996 Unit seven  Animal Form and Function

Hormones and the 45
Endocrine System

Figure 45.1  What makes male and female elephant seals look so different?

Key Concepts The Body’s Long-Distance Regulators

45.1 Hormones and other signaling Although we often distinguish animals of different species by their appearance, in
many species the females and males look quite different from each other. Such is
molecules bind to target the case for elephant seals (Mirounga angustirostris), shown in Figure 45.1. The male
receptors, triggering specific is much larger than the female, and only he has the prominent proboscis for which
response pathways the species is named. Males are also far more territorial and aggressive than females.
A sex-determining gene on the Y chromosome makes a seal embryo male. But how
45.2 Feedback regulation and does the presence of this gene lead to male size, shape, and behavior? The answer
to this and many other questions about biological processes involves signaling
coordination with the nervous molecules called hormones (from the Greek horman, to excite).
system are common in hormone
pathways In animals, hormones are secreted into the extracellular fluid, circulate in the
blood (or hemolymph), and communicate regulatory messages throughout the
45.3 Endocrine glands respond to body. In the case of the elephant seal, increased secretion of particular hormones
at puberty triggers sexual maturation as well as the accompanying changes that
diverse stimuli in regulating result in sexual dimorphism, the distinct appearance of adult females and males.
homeostasis, development, Hormones influence much more than sex and reproduction, however. For exam-
and behavior ple, when seals, humans, and other mammals are stressed, are dehydrated, or have
low blood sugar levels, hormones coordinate the physiological responses that
Male elephant seals sparring restore balance in our bodies.

When you see this blue icon, log in to MasteringBiology Get Ready for This Chapter
and go to the Study Area for digital resources.

997

Each hormone binds to specific receptors in the body. Figure 45.2  Intercellular communication by secreted
Although a given hormone can reach all cells of the body, molecules. In each type of signaling, secreted molecules ( ) bind
only some cells have receptors for that hormone. A hormone to a specific receptor protein ( ) expressed by target cells. Some
elicits a response—such as a change in metabolism—in receptors are located inside cells, but for simplicity, here all are
specific target cells, those that have the matching receptor. drawn on the cell surface.
Cells lacking a receptor for that hormone are unaffected.
Blood RESPONSE
Chemical signaling by hormones is the function of the vessel
endocrine system, one of the two basic systems for commu-
nication and regulation in the animal body. The other major (a) In endocrine signaling, secreted molecules diffuse into the blood-
communication and control system is the nervous system, stream and trigger responses in target cells anywhere in the body.
a network of specialized cells—neurons—that transmit sig-
nals along dedicated pathways. These signals in turn regulate RESPONSE
neurons, muscle cells, and endocrine cells. Because signaling (b) In paracrine signaling, secreted molecules diffuse locally and
by neurons can regulate the release of hormones, the nervous
and endocrine systems often overlap in function. trigger a response in neighboring cells.

In this chapter, we’ll begin with an overview of the RESPONSE
different types of chemical signaling in animals. We’ll then (c) In autocrine signaling, secreted molecules diffuse locally and trigger
explore how hormones regulate target cells, how hormone
secretion is regulated, and how hormones help main- a response in the cells that secrete them.
tain homeostasis. We’ll also consider the ways in which Synapse
endocrine and nervous system activities are coordinated
as well as examine how hormones regulate growth and Neuron
development.
RESPONSE
Concept  45.1
(d) In synaptic signaling, neurotransmitters diffuse across synapses
Hormones and other signaling and trigger responses in cells of target tissues (neurons, muscles,
molecules bind to target receptors, or glands).
triggering specific response pathways Neurosecretory
cell
To begin, we’ll examine the diverse ways that animal cells use
chemical signals to communicate. Blood RESPONSE
vessel
Intercellular Communication
(e) In neuroendocrine signaling, neurohormones diffuse into the
Communication between animal cells via secreted signals is bloodstream and trigger responses in target cells anywhere in
often classified by two criteria: the type of secreting cell and the body.
the route taken by the signal in reaching its target. Figure 45.2
illustrates five forms of signaling distinguished in this manner. Paracrine and Autocrine Signaling

Endocrine Signaling Many types of cells produce and secrete local regulators,
molecules that act over short distances, reach their target
In endocrine signaling (see Figure 45.2a), hormones secreted cells solely by diffusion, and act on their target cells within
into extracellular fluid by endocrine cells reach target cells
via the bloodstream (or hemolymph). One function of
endocrine signaling is to maintain homeostasis. Hormones
regulate properties that include blood pressure and volume,
energy metabolism and allocation, and solute concentra-
tions in body fluids. Endocrine signaling also mediates
responses to environmental stimuli, regulates growth and
development, and, as discussed above, triggers physical
and behavioral changes underlying sexual maturity and
reproduction.

998 Unit seven  Animal Form and Function

seconds or even milliseconds. Local regulators play roles Figure 45.3  Signaling by pheromones. Using their lowered
in many physiological processes, including blood pressure antennae, these Asian army ants (Leptogenys distinguenda) follow
regulation, nervous system function, and reproduction. a pheromone-marked trail as they carry pupae and larvae to a new
nest site.
Depending on the target cell, signaling by local regulators
can be either paracrine or autocrine. In paracrine signal- potential mates. The polyphemus moth (Antheraea polyphe-
ing (from the Greek para, to one side of), target cells lie near mus) provides a noteworthy example: The sex pheromone
the secreting cell (see Figure 45.2b). In autocrine signaling released into the air by a female enables her to attract a male
(from the Greek auto, self), the secreting cells themselves are of the species from up to 4.5 km away. You’ll read more
the target cells (see Figure 45.2c). about pheromone function when we take up the topic
of animal behavior in Chapter 51.
One group of local regulators with diverse and widespread
functions are the prostaglandins. In the immune system, Chemical Classes of Local Regulators
for example, prostaglandins promote inflammation and the and Hormones
sensation of pain in response to injury. Drugs that block pros-
taglandin synthesis, such as aspirin and ibuprofen, prevent What kinds of molecules convey signals in animal bodies?
these activities, producing both anti-inflammatory and Let’s take a look.
pain-relieving effects.
Classes of Local Regulators
Prostaglandins also help regulate the aggregation of plate-
lets, one step in the formation of blood clots. Because blood Prostaglandins are modified fatty acids. Many other local
clots in vessels that supply the heart can block blood flow, regulators are polypeptides, including cytokines, which
causing a heart attack (see Concept 42.4), some physicians enable immune cell communication (see Figure 43.16 and
recommend that people at risk for a heart attack take aspirin Figure 43.17), and growth factors, which promote cell
on a regular basis. growth, division, and development. Some local regulators
are gases.
Synaptic and Neuroendocrine Signaling
Nitric oxide (NO), a gas, functions in the body as both
Secreted molecules are essential for the function of the ner- a local regulator and a neurotransmitter. When the level of
vous system. Neurons communicate with target cells, such oxygen in the blood falls, endothelial cells in blood vessel
as other neurons and muscle cells, via specialized junctions walls synthesize and release NO. After diffusing into the sur-
called synapses. At most synapses, neurons secrete molecules rounding smooth muscle cells, NO activates an enzyme that
called neurotransmitters that diffuse a very short distance relaxes the cells. The result is vasodilation, which increases
(a fraction of a cell diameter) and bind to receptors on the blood flow to tissues.
target cells (see Figure 45.2d). Such synaptic signaling is central
to sensation, memory, cognition, and movement (as we’ll In human males, NO’s ability to promote vasodilation
explore in Chapters 48–50). enables sexual function by increasing blood flow into the
penis, producing an erection. The drug Viagra (sildenafil
In neuroendocrine signaling, neurons called neurosecretory citrate), a treatment for male erectile dysfunction, sustains
cells secrete neurohormones, which diffuse from nerve cell an erection by prolonging activity of the NO response
endings into the bloodstream (see Figure 45.2e). One example pathway.
of a neurohormone is antidiuretic hormone, which functions
in kidney function and water balance as well as courtship
behavior. Many neurohormones regulate endocrine signal-
ing, as we’ll discuss later in this chapter.

Signaling by Pheromones

Not all secreted signaling molecules act within the body.
Members of a particular animal species sometimes commu-
nicate with each other via pheromones, chemicals that
are released into the external environment. For example,
when a foraging ant discovers a new food source, it marks
its path back to the nest with a pheromone. Ants also use
pheromones for guidance when a colony migrates to a new
location (Figure 45.3).

Pheromones serve a wide range of functions that include
defining territories, warning of predators, and attracting

chapter 45  Hormones and the Endocrine System 999