43 Flashcards
innate immunity
All animals have innate immunity, a defense that is active immediately upon infection and is the same whether or
not the pathogen has been encountered previously. Innate
immunity includes an outer covering, such as a skin or shell,
that provides a significant barrier to entry by microbes. Sealing off the entire body surface is impossible, however, because gas exchange, nutrition, and reproduction require
openings to the environment. Chemical secretions that trap
or kill microbes guard the body’s entrances and exits, while
the linings of the digestive tract, airway, and other exchange
surfaces provide additional barriers to infection
- In innate immunity, a small preset group of receptor proteins bind to molecules or structures that are absent from animal bodies but common to a group of viruses, bacteria, or
other microbes. Binding of an innate immune receptor to a
foreign molecule activates internal defenses, enabling responses to a very broad range of pathogens.
adaptive immunity
- A different type of molecular recognition provides the basis
for adaptive immunity, a defense found only in vertebrates. Animals with adaptive immunity produce a vast arsenal of receptors, each of which recognizes a feature typically
found only on a particular part of a particular molecule in a
particular pathogen. As a result, recognition and response in
adaptive immunity occur with tremendous specificity. - The adaptive immune response, also known as the acquired
immune response, is activated after the innate immune response and develops more slowly
innate immunity in insects
insects rely on their exoskeleton as a first line of defense against
infection. Composed largely of the polysaccharide chitin, the
exoskeleton provides an effective barrier defense against most
pathogens. A chitin-based barrier is also present in the insect
intestine, where it blocks infection by many pathogens ingested with food. Lysozyme, an enzyme that breaks down
bacterial cell walls, further protects the insect digestive system.
hemocytes
Any pathogen that breaches an insect’s barrier defenses encounters a number of internal immune defenses. Immune
cells called hemocytes travel throughout the body in the hemolymph, the insect circulatory fluid. Some hemocytes carry
out a defense called phagocytosis, the cellular ingestion
and digestion of bacteria and other foreign substances
antimicrobial peptides
- innate immunity in insects
- short chains of amino acids.
The antimicrobial peptides circulate throughout the body of
the insect (Figure 43.4) and inactivate or kill fungi and bacteria by disrupting their plasma membranes. - the synthesis of a single type of antimicrobial
peptide in the fly’s body could provide an effective immune
defense. They also showed that particular antimicrobial peptides act against different kinds of pathogens.
Immune cells of insects
bind to molecules found only in
the outer layers of fungi or bacteria. Fungal cell walls contain
certain unique polysaccharides, whereas bacterial cell walls
have polymers containing combinations of sugars and amino acids not found in animal cells. Such macromolecules serve
as identity tags in the process of pathogen recognition. Insect
immune cells secrete specialized recognition proteins, each of
which binds to a macromolecule characteristic of fungi or a
broad class of bacteria.
barrier defenses in mammals
- In mammals, epithelial tissues block the entry of many
pathogens. These barrier defenses include not only the skin
but also the mucous membranes lining the digestive, respiratory, urinary, and reproductive tracts. Certain cells of the
mucous membranes produce mucus, a viscous fluid that enhances defenses by trapping microbes and other particles. In
the trachea, ciliated epithelial cells sweep mucus and any entrapped microbes upward, helping prevent infection of the
lungs. Saliva, tears, and mucous secretions that bathe various
exposed epithelia provide a washing action that also inhibits
colonization by fungi and bacteria. - Lysozyme in tears, saliva, and mucous secretions destroys the cell walls of susceptible bacteria as they
enter the openings around the eyes or the upper respiratory
tract. (First, gases produced in the lysosome poison the engulfed pathogens. Second, lysozyme and
other enzymes in the lysosome degrade the components of
the pathogens.) - Microbes in food or water and those in swallowed
mucus must also contend with the acidic environment of the
stomach, which kills most of them before they can enter the
intestines. Similarly, secretions from oil and sweat glands
give human skin a pH ranging from 3 to 5, acidic enough to
prevent the growth of many bacteria.
TLR
- Pathogens entering the mammalian body are subject to
phagocytosis. Phagocytic cells detect fungal or bacterial components using several types of receptors, some of which are
very similar to the Toll receptor of insects. Each mammalian
Toll-like receptor (TLR) binds to fragments of molecules
characteristic of a set of pathogens - In each case, the recognized macromolecule
is normally absent from the vertebrate body and is an essential component of certain groups of pathogens.
main types of phagocytic cells
The two main types of phagocytic cells in the mammalian
body are neutrophils and macrophages. Neutrophils, which
circulate in the blood, are attracted by signals from infected
tissues and then engulf and destroy the infecting pathogens.
Macrophages (“big eaters”), like the one shown in
Figure 43.1, are larger phagocytic cells. Some migrate throughout the body, whereas others reside permanently in organs
and tissues where they are likely to encounter pathogens.
other phagocytic cells
Two other types of phagocytic cells—dendritic cells and
eosinophils—provide additional functions in innate defense.
Dendritic cells mainly populate tissues, such as skin, that
contact the environment. They stimulate adaptive immunity against pathogens they encounter and engulf, as we’ll explore shortly. Eosinophils, often found beneath mucosal surfaces, have low phagocytic activity but are important in
defending against multicellular invaders, such as parasitic
worms. Upon encountering such parasites, eosinophils discharge destructive enzymes.
natural killer cells
Cellular innate defenses in vertebrates also involve natural
killer cells. These cells circulate through the body and detect
the abnormal array of surface proteins characteristic of some
virus-infected and cancerous cells. Natural killer cells do not engulf stricken cells. Instead, they release chemicals that lead to
cell death, inhibiting further spread of the virus or cancer.
lymphatic system
Many cellular innate defenses of vertebrates involve the
lymphatic system, a network that distributes the fluid called
lymph throughout the body (Figure 43.7). Some macrophages
reside in the structures called lymph nodes, where they engulf
pathogens that have flowed from the interstitial fluid into the
lymph. Dendritic cells reside outside the lymphatic system but
migrate to lymph nodes after interaction with pathogens.
Within the lymph nodes, dendritic cells interact with other
immune cells, stimulating adaptive immunity.
antimicrobial peptides in mammals
In mammals, pathogen recognition triggers the production
and release of a variety of peptides and proteins that attack pathogens or impede their reproduction. Some of these defense molecules function like the antimicrobial peptides of
insects, damaging broad groups of pathogens by disrupting
membrane integrity. Others, including the interferons and
complement proteins, are unique to vertebrate immune
systems
interferons
Interferons are proteins that provide innate defense by
interfering with viral infections. Virus-infected body cells secrete interferons, which induce nearby uninfected cells to
produce substances that inhibit viral reproduction. In this
way, interferons limit the cell-to-cell spread of viruses in the
body, helping control viral infections such as colds and influenza. Some white blood cells secrete a different type of interferon that helps activate macrophages, enhancing their
phagocytic ability.
complement system
- The infection-fighting complement system consists of
roughly 30 proteins in blood plasma. These proteins circulate
in an inactive state and are activated by substances on the
surface of many microbes. Activation results in a cascade of
biochemical reactions that can lead to lysis (bursting) of invading cells - also functions in inflammatory response and other adaptive defenses
inflammatory response
The pain and swelling that alert you to a splinter under your
skin are the result of a local inflammatory response, the
changes brought about by signaling molecules released upon
injury or infection
histamine
One important inflammatory signaling molecule is histamine, which is stored in the
granules (vesicles) of mast cells, found in connective tissue.
Histamine released at sites of damage triggers nearby blood
vessels to dilate and become more permeable.
cytokines
Activated
macrophages and neutrophils discharge cytokines, signaling
molecules that enhance an immune response. These cytokines
promote blood flow to the site of injury or infection. The increase in local blood supply causes the redness and increased
skin temperature typical of the inflammatory response. Blood-engorged capillaries
leak fluid into neighboring tissues, causing swelling.
pus
During inflammation, cycles of signaling and response
transform the site. Activated complement proteins promote
further release of histamine, attracting more phagocytic cells
that enter injured tissues (see Figure 43.8) and carry out additional phagocytosis. At the same time, enhanced blood flow
to the site helps deliver antimicrobial peptides. The result is
an accumulation of pus, a fluid rich in white blood cells, dead
pathogens, and cell debris from damaged tissue.
fever
Another systemic inflammatory response is fever. In response to certain pathogens, substances released by activated
macrophages cause the body’s thermostat to reset to a higher
temperature (see Chapter 40). The benefits of the resulting
fever are still a subject of debate. One of several competing
hypotheses is that an elevated body temperature may enhance phagocytosis and, by speeding up chemical reactions,
accelerate tissue repair.
septic shock
Certain bacterial infections can induce an overwhelming
systemic inflammatory response, leading to a life-threatening
condition called septic shock. Characterized by very high fever,
low blood pressure, and poor blood flow through capillaries,
septic shock occurs most often in the very old and the very
young.
Evasion of Innate Immunity by Pathogens
- For example,
the outer capsule that surrounds certain bacteria interferes
with molecular recognition and phagocytosis - Some bacteria, after being engulfed by a host
cell, resist breakdown within lysosomes. An example is the
bacterium that causes tuberculosis (TB).
lymphocytes
Vertebrates are unique in having adaptive immunity in addition to innate immunity. The adaptive response relies on T cells and B cells, which are types of white blood cells called lymphocytes
lymphocytes location
Like all
blood cells, lymphocytes originate from stem cells in the bone marrow. Some lymphocytes
migrate from the bone marrow to the thymus, an organ in the
thoracic cavity above the heart (see Figure 43.7). These lymphocytes 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 killer
cells active in innate immunity.)
antigen
Any substance that elicits a response from a B cell or T cell is
called an antigen.
- Antigens are usually foreign and are typically large molecules, either proteins or polysaccharides. Many antigens protrude from the surface of foreign cells or viruses. Other
antigens, such as toxins secreted by bacteria, are released into
the extracellular fluid.
antigen receptors
In adaptive immunity, recognition occurs
when a B cell or T cell binds to an antigen, such as a bacterial
or viral protein, via a protein called an antigen receptor. An
antigen receptor is specific enough to bind to just one part of
one molecule from a particular pathogen, such as a species of
bacteria or strain of virus.
- Although the cells of the immune system produce millions of different antigen receptors, all of
the antigen receptors made by a single B or T cell are identical.
- Infection by a virus, bacterium, or other pathogen triggers activation of B and T cells with antigen receptors specific for parts
of that pathogen.
- there are actually about 100,000 antigen
receptors on the surface of a single B or T cell.
epitope
The small, accessible portion of an antigen that binds to
an antigen receptor is called an epitope, or antigenic determinant. An example is a group of amino acids in a particular
protein. A single antigen usually has several different epitopes, each binding a receptor with a different specificity. Because all antigen receptors produced by a single B cell or T
cell are identical, they bind to the same epitope. Each B cell
or T cell thus displays specificity for a particular epitope, enabling it to respond to any pathogen that produces molecules
containing that same epitope.
- Many noncovalent bonds between
an epitope and the binding surface provide a stable and specific interaction. Differences in the amino acid sequences of
variable regions provide the variation in binding surfaces
that enables this highly specific binding.
B cell antigen receptor structure
Each B cell antigen receptor is a Y-shaped molecule consisting
of four polypeptide chains: two identical heavy chains and
two identical light chains, with disulfide bridges linking
the chains together (Figure 43.9). A transmembrane region
near one end of each heavy chain anchors the receptor in the
cell’s plasma membrane. A short tail region at the end of the
heavy chain extends into the cytoplasm.
- each
B cell antigen receptor has two identical antigen-binding sites
B cell: C region
The light and heavy chains each have a constant (C) region,
where amino acid sequences vary little among the receptors
on different B cells. The C region includes the cytoplasmic
tail and transmembrane region of the heavy chain and all of
the disulfide bridges.
B cell: V region
Within the two tips of the Y shape, the
light and heavy chains each have a variable (V) region, so
named because its amino acid sequence varies extensively
from one B cell to another. Together, parts of a heavy-chain
V region and a light-chain V region form an asymmetrical
binding site for an antigen.
antibody/Ig
The binding of a B cell antigen receptor to an antigen is
an early step in B cell activation, leading eventually to formation of cells that secrete a soluble form of the receptor
(Figure 43.10a). This secreted protein is called an antibody, or immunoglobulin (Ig). Antibodies have the same
Y-shaped organization as B cell antigen receptors, but they
are secreted rather than membrane bound. It is the antibodies, rather than the B cells themselves, that actually help defend against pathogens.
T cell structure
For a T cell, the antigen receptor consists of two different
polypeptide chains, an a chain and a b chain, linked by a
disulfide bridge (Figure 43.11). Near the base of the T cell
antigen receptor (often called simply a T cell receptor) is a
transmembrane region that anchors the molecule in the cell’s
plasma membrane. At the outer tip of the molecule, the
variable (V) regions of α and β chains together form a single
antigen-binding site. The remainder of the molecule is made
up of the constant (C) regions
T vs B cell antigen receptors
Whereas the antigen receptors of B cells bind to
epitopes of intact antigens circulating in body fluids, those of T cells bind only 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 an
MHC (major histocompatibility complex) molecule
Recognition of protein antigens by T cells
begins when a
pathogen or part of a pathogen either infects or is taken in by
a host cell (Figure 43.12a). Inside the host cell, enzymes in
the cell cleave the antigen into smaller peptides. Each peptide, called an antigen fragment, then binds to an MHC molecule inside the cell. Movement of the MHC molecule and
bound antigen fragment to the cell surface results in
antigen presentation, the display of the antigen fragment
in an exposed groove of the MHC protein.
- If the cell displaying an antigen fragment encounters
a T cell with the right specificity, the antigen receptor on the
T cell can bind to both the antigen fragment and the MHC
molecule. This interaction of an MHC molecule, an antigen
fragment, and an antigen receptor is necessary for a T cell to
participate in an adaptive immune response
four major characteristics of adaptive immunity
First, there is an immense diversity of lymphocytes
and receptors, enabling the immune system to detect
pathogens never before encountered. Second, adaptive immunity normally has self-tolerance, the lack of reactivity
against an animal’s own molecules and cells. Third, cell proliferation triggered by activation greatly increases the number of B and T cells specific for an antigen. Fourth, there is a
stronger and more rapid response to an antigen encountered
previously, due to a feature known as immunological memory.
gene segments coding for the chains
The capacity to generate diversity is built into the structure of Ig genes. A receptor light chain is encoded by three
gene segments: a variable (V) segment, a joining ( J) segment, 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 lightchain gene contains a single C segment, 40 different V segments, and 5 different J segments. These alternative copies
of the V and J segments are arranged within the gene in a series (Figure 43.13). Because a functional gene is built
from one copy of each type of segment, the pieces can be
combined in 200 different ways (40 V 5 J 1 C). The
number of different heavy-chain combinations is even
greater, resulting in even more diversity.
recombinase
Assembling a functional Ig gene requires rearranging the
DNA. Early in B cell development, an enzyme complex called
recombinase links one light-chain V gene segment to one J gene
segment. This recombination event eliminates the long stretch
of DNA between the segments, forming a single exon that is
part V and part J. Because there is only an intron between the J
and C DNA segments, no further DNA rearrangement is required. Instead, the J and C segments of the RNA transcript will
be joined when splicing removes the intervening RNA (see
Figure 17.11 to review RNA splicing).
Recombinase acts randomly, linking any one of the 40 V
gene segments to any one of the 5 J gene segments. Heavychain genes undergo a similar rearrangement. In any given
cell, however, only one allele of a light-chain gene and one
allele of a heavy-chain gene are rearranged
formation of antigen receptr
After both the light- and heavy-chain genes have rearranged, antigen receptors can be synthesized. The rearranged
genes are transcribed, and the transcripts are processed for
translation. Following translation, the light chain and heavy chain assemble together, forming an antigen receptor (see
Figure 43.13). Each pair of randomly rearranged heavy and
light chains results in a different antigen-binding site
self tolerance
as
lymphocytes mature in the bone marrow or thymus, their
antigen receptors are tested for self-reactivity. Some B and
T cells with receptors specific for the body’s own molecules
are destroyed by apoptosis, which is a programmed cell death
(see Chapter 11). The remaining self-reactive lymphocytes
are typically rendered nonfunctional, leaving only those that
react to foreign molecules. Since the body normally lacks mature lymphocytes that can react against its own components,
the immune system is said to exhibit self-tolerance.
antigen matching
an antigen is presented to a steady stream of lymphocytes in the lymph nodes
(see Figure 43.7) until a match is made. A successful match
then triggers changes in cell number and a
effctor cells
The binding of an antigen receptor to an epitope initiates
events that activate the lymphocyte. Once activated, a B cell or
T cell undergoes multiple cell divisions. For each activated cell,
the result of this proliferation is a clone, a population of cells
that are identical to the original cell. Some cells from this clone
become effector cells, short-lived cells that take effect immediately against the antigen and any pathogens producing that
antigen. The effector forms of B cells are plasma cells, which
secrete antibodies. The effector forms of T cells are helper
T cells and cytotoxic T cells, whose roles we’ll explore in
Concept 43.3. The remaining cells in the clone become
memory cells, long-lived cells that can give rise to effector
cells if the same antigen is encountered later in the animal’s life
clonal selection
an encounter with an antigen selects
which lymphocyte will divide to produce a clonal population
of thousands of cells specific for a particular epitope.
primary immune response
Prior exposure to an antigen alters the speed, strength, and
duration of the immune response. The production of effector
cells from a clone of lymphocytes during the first exposure to
an antigen is the basis for the primary immune response.
The primary response peaks about 10–17 days after the initial
exposure. During this time, selected B cells and T cells give rise
to their effector forms
2ndary immune response
If an individual is exposed again to the
same antigen, the response is faster (typically peaking only
2–7 days after exposure), of greater magnitude, and more prolonged. This is the secondary immune response, a hallmark
of adaptive, or acquired, immunity. Because selected B cells give rise to antibody-secreting effector cells, measuring the concentrations of specific antibodies in blood over time distinguishes
the primary and secondary immune responses
The secondary immune response relies on
the reservoir of
T and B memory cells generated following initial exposure to
an antigen. Because these cells are long-lived, they provide
the basis for immunological memory, which can span many
decades. (Effector cells have much shorter life spans, which is
why the immune response diminishes after an infection is
overcome.) If an antigen is encountered again, memory cells
specific for that antigen enable the rapid formation of clones
of thousands of effector cells also specific for that antigen,
thus generating a greatly enhanced immune defense.
humoral immune response
The activities of B and T lymphocytes
produce a humoral immune response and a cell-mediated immune response. The humoral immune response occurs in
the blood and lymph, which were long ago called body humors (fluids). In the humoral response, antibodies help neutralize or eliminate toxins and pathogens in the blood and
lymph
cell mediated immune response
In the cell-mediated immune response, specialized T cells destroy infected host cells.
helper T cell
A type of T cell called a helper T cell triggers both the humoral and cell-mediated immune responses. Helper T cells
themselves do not carry out those responses. Instead, signals
from helper T cells initiate production of antibodies that neutralize pathogens and activate T cells that kill infected cells.
Two requirements must be met for a helper T cell to activate adaptive immune responses.
First, a foreign molecule
must be present that can bind specifically to the antigen receptor of the T cell. Second, this antigen must be displayed
on the surface of an antigen-presenting cell. The antigenpresenting cell can be a dendritic cell, macrophage, or B cell.
MHC classes
When host cells are infected, they too display antigens on
their surface. What then distinguishes an antigen-presenting
cell? The answer lies in the existence of two classes of MHC
molecules. Most body cells have only class I MHC molecules,
but antigen-presenting cells have both class I and class II
MHC molecules. The class II molecules provide a molecular
signature by which an antigen-presenting cell is recognized.
interaction btwn helper T cell and antigen-presenting cell
The antigen receptors on the surface of the helper T cell bind
to the antigen fragment and to the class II MHC molecule displaying that fragment on the antigen-presenting cell. At the
same time, an accessory protein on the helper T cell surface
binds to the class II MHC molecule, helping keep the cells
joined. As the two cells interact, signals in the form of cytokines are exchanged in both directions.
The different types of antigen-presenting cells interact
with helper T cells in distinct contexts
- Antigen presentation by a dendritic cell or macrophage activates a helper T cell.
The helper T cell then proliferates, forming a clone of activated helper T cells. - The B cells present antigens to already
activated helper T cells, which in turn activate the B cells
themselves. Activated helper T cells also help stimulate cytotoxic T cells
cytotoxic T cells
In the cell-mediated immune response, cytotoxic T cells
are the effector cells. The term cytotoxic refers to their use of
toxic gene products to kill infected cells.
activation of cytotoxic T cells
- To become active, they require signaling molecules from helper T cells as well as
interaction with a cell that presents an antigen. Once activated, cytotoxic T cells can eliminate cells that are infected
by viruses or other intracellular pathogens. - Fragments of foreign proteins produced in infected host
cells associate with class I MHC molecules and are displayed
on the cell surface, where they can be recognized by cytotoxic T cells (Figure 43.17). As with helper T cells, cytotoxic
T cells have an accessory protein that binds to the MHC molecule, helping keep the two cells in contact while the T cell is
activated.
targeted destruction of an infected host cell by a cytotoxic T cell
involves the secretion of proteins that disrupt
membrane integrity and trigger apoptosis (see Figure 43.17).
The death of the infected cell not only deprives the pathogen
of a place to reproduce, but also exposes cell contents to circulating antibodies, which mark them for disposal. After destroying an infected cell, the cytotoxic T cell can move on
and kill other cells infected with the same pathogen
Activation of the humoral immune response
typically involves
B cells and helper T cells as well as proteins on the surface of
pathogens. As depicted in Figure 43.18, B cell activation by an
antigen is aided by cytokines secreted from helper T cells that
have encountered the same antigen. Stimulated by both an
antigen and cytokines, the B cell proliferates and differentiates
into memory B cells and antibody-secreting effector cells
called plasma cells.
The pathway for antigen processing and display in B cells
differs from that in other antigen-presenting cells
A macrophage or dendritic cell can present fragments from a wide variety of protein antigens, whereas a B cell presents only the
antigen to which it specifically binds. When an antigen first
binds to receptors on the surface of a B cell, the cell takes in a
few foreign molecules by receptor-mediated endocytosis (see
Figure 7.22). The class II MHC protein of the B cell then presents an antigen fragment to a helper T cell. This direct cell-tocell contact is usually critical to B cell activation
An activated B cell gives rise to
thousands of identical
plasma cells. These plasma cells stop expressing a membranebound antigen receptor and begin producing and secreting
antibodies. Furthermore, most antigens recognized by B cells contain multiple epitopes. An exposure to
a single antigen therefore normally activates a variety of
B cells, with different plasma cells producing antibodies directed against different epitopes on the common antigen.
antibody function
Antibodies do not kill pathogens, but by binding to antigens,
they mark pathogens in various ways for inactivation or destruction
neutralization
In the simplest of these activities, neutralization,
antibodies bind to viral surface proteins (Figure 43.19, left).
The bound antibodies prevent infection of a host cell, thus
neutralizing the virus. Similarly, antibodies sometimes bind to
toxins released in body fluids, preventing the toxins from
entering body cells
opsonization
In another process, called opsonization, antibodies bound to antigens on bacteria present a readily recognized structure for macrophages or neutrophils and therefore increase phagocytosis (Figure 43.19, middle). Because each antibody has two antigen-binding sites, antibodies sometimes also facilitate phagocytosis by linking bacterial cells, virus particles, or other foreign substances into aggregates
antibodies and compement system
Antibodies sometimes work together with the proteins of
the complement system to dispose of pathogens. (The name
complement reflects the fact that these proteins increase the
effectiveness of antibody-directed attacks on bacteria.) Binding of a complement protein to an antigen-antibody complex on a foreign cell (or an enveloped virus) triggers a
cascade in which each protein of the complement system activates the next protein.
membrane attack complex
Ultimately, activated complement
proteins generate a membrane attack complex that forms a
pore in the membrane of the foreign cell. Ions and water rush
into the cell, causing it to swell and lyse (Figure 43.19,
right).Whether activated as part of innate defenses or as part
of adaptive defenses, this cascade of complement protein activity results in the lysis of foreign cells and produces factors
that promote inflammation or stimulate phagocytosis.
antibodies and phagocytosis
When antibodies facilitate phagocytosis (see Figure 43.19,
middle), they also help fine-tune the humoral immune response. Recall that phagocytosis enables macrophages and
dendritic cells to present antigens to and stimulate helper
T cells, which in turn stimulate the very B cells whose antibodies contribute to phagocytosis. This positive feedback between innate and adaptive immunity contributes to a
coordinated, effective response to infection.
mechanism by which antibodies can bring
about the death of infected body cells
When a virus uses a
cell’s biosynthetic machinery to produce viral proteins, these
viral products can appear on the cell surface. If antibodies specific for epitopes on these viral proteins bind to the exposed
proteins, the presence of bound antibody at the cell surface can
recruit a natural killer cell. The natural killer cell then releases
proteins that cause the infected cell to undergo apoptosis.
B cells can express five different forms of immunoglobulin
Ig
For a given B cell, each form or class has an identical
antigen-binding specificity, but a distinct heavy-chain C region. The B cell antigen receptor, known as IgD, is membrane
bound. The other four classes consist of soluble antibodies.
IgM is the first class of soluble antibody produced. IgG,
which follows next, is the most abundant antibody in blood
- IgA, IgE
active immunity
the defenses that arise when a
pathogen infects the body and prompts a primary or secondary immune response.
passive immunity
In contrast, a different type of immunity results when the IgG antibodies in the blood of a
pregnant female cross the placenta to her fetus. The transferred antibodies can immediately react with any pathogens
for which they are specific. This protection is called passive
immunity because the antibodies provided by the mother
guard against pathogens that have never infected the newborn.
Because passive immunity does not involve the recipient’s B and T cells, it persists only as long as the transferred antibodies last (a few weeks to a few months).
IgA
After giving birth, a nursing mother continues to transfer
protection against disease to her infant. IgA antibodies present in breast milk provide additional passive immunity to the
infant’s digestive tract while the infant’s immune system develops. Later in life, IgA functions in active immunity: IgA
antibodies secreted in tears, saliva, and mucus protect the
mucous membranes of both males and females.
immunization
Both active immunity and passive immunity can be induced artificially. Active immunity can develop from the introduction of antigens into the body through immunization.
In 1796, Edward Jenner noted that milkmaids who had cowpox, a mild disease usually seen only in cows, did not contract
smallpox, a far more dangerous disease. In the first documented immunization (vaccination), Jenner used the cowpox virus to induce adaptive immunity against the closely related smallpox virus.
artificial passive immunization
antibodies from an immune animal are injected into a nonimmune animal
polyclonal antibodies
Some antibody tools are polyclonal: They are the products of many different clones of plasma cells, each specific
for a different epitope (Figure 43.21). Antibodies that an animal produces after exposure to a microbial antigen are polyclonal.
monoclonal antibodies
In contrast, other antibody tools are monoclonal: They
are prepared from a single clone of B cells grown in culture.
The monoclonal antibodies produced by such a culture
are identical and specific for the same epitope on an antigen.
home pregnancy kits
use monoclonal antibodies to detect human
chorionic gonadotropin
(hCG). Because hCG is
produced as soon as an
embryo implants in the
uterus (see Chapter 46),
the presence of this hormone in a woman’s
urine is a reliable indicator for a very early stage
of pregnancy.
ABO blood groups structure
red blood cells are designated as type A if they
have the type A carbohydrate on their surface. Similarly, the
type B carbohydrate is found on type B red blood cells; both
A and B carbohydrates are found on type AB red blood cells;
and neither carbohydrate is found on type O red blood cells
blood transfusions and blood type
univ donor: O-; receipient: AB+
- It turns out that certain bacteria normally present in
the body have epitopes very similar to the A and B carbohydrates. By responding to the bacterial epitope similar to the
B carbohydrate, a person with type A blood makes antibodies
that will react with the type B carbohydrate. No antibodies
are made against the bacterial epitope similar to the type A
carbohydrate because lymphocytes reactive with the body’s
own molecules are inactivated or eliminated during development. If the person with type A blood receives a transfusion
of type B blood, that person’s anti-B antibodies cause an immediate and devastating transfusion reaction. The transfused
red blood cells undergo lysis, which can lead to chills, fever,
shock, and kidney malfunction. By the same token, anti-A
antibodies in the donated type B blood will act against the recipient’s type A red blood cells
- (O can’t receive transfusions of any other type)
Tissue and Organ Transplants
MHC
molecules stimulate the immune response that leads to rejection. Each vertebrate species has many alleles for each MHC
gene, enabling presentation of antigen fragments that vary in
shape and net electrical charge. This diversity of MHC molecules almost guarantees that no two people, except identical
twins, will have exactly the same set. Thus, in the vast majority of graft and transplant recipients, some MHC molecules
on the donated tissue are foreign to the recipient. To minimize rejection, physicians use donor tissue bearing MHC
molecules that match those of the recipient as closely as possible. In addition, the recipient takes medicines that suppress
immune responses (but also leave the recipient more susceptible to infections).
Transplants of bone marrow from one person to another
can also cause an immune reaction, but for a different reason
Bone marrow transplants are used to treat leukemia and
other cancers as well as various hematological (blood cell)
diseases. Prior to receiving transplanted bone marrow, the recipient is typically treated with radiation to eliminate his or
her own bone marrow cells, thus destroying the source of abnormal cells. This treatment effectively obliterates the recipient’s immune system, leaving little chance of graft rejection.
graft versus host reaction
lymphocytes in the donated marrow may react
against the recipient. This graft versus host reaction is limited if
the MHC molecules of the donor and recipient are well
matched. Bone marrow donor programs continually seek volunteers because the great variability of MHC molecules
makes a diverse pool of donors essential.
allergens
Allergies are exaggerated (hypersensitive) responses to certain
antigens called allergens. The most common allergies involve antibodies of the IgE class. Hay fever, for instance, occurs when plasma cells secrete IgE antibodies specific for
antigens on the surface of pollen grains (Figure 43.22). Some
IgE antibodies attach by their base to mast cells in connective
tissues. Pollen grains that enter the body later attach to the
antigen-binding sites of these IgE antibodies. This attachment links adjacent IgE molecules, inducing the mast cell to
release histamine and other inflammatory chemicals from
granules (vesicles). Acting on a variety of cell types, these signals bring about the typical allergy symptoms: sneezing,
runny nose, teary eyes, and smooth muscle contractions that
can result in breathing difficulty
antihistamines
Drugs called antihistamines
diminish allergy symptoms (and inflammation) by blocking
receptors for histamine.
anaphylactic
shock
- a whole-body, life-threatening reaction that can occur
within seconds of exposure to an allergen. Anaphylactic
shock develops when widespread release of mast cell contents triggers abrupt dilation of peripheral blood vessels,
causing a precipitous drop in blood pressure, as well as constriction of bronchioles. Death may occur within minutes
due to lack of blood flow and the inability to breathe. - People with severe hypersensitivities often carry syringes containing the
hormone epinephrine, which counteracts this allergic response
autoimmune disease
In some people, the immune
system is active against particular molecules of the body,
causing an autoimmune
disease. Such a loss of selftolerance has many forms.
lupus
In systemic lupus erythematosus, commonly called lupus, the immune system generates antibodies against histones and DNA released by the normal breakdown of body cells. These self-reactive antibodies cause skin rashes, fever, arthritis, and kidney dysfunction.
rheumatoid arthritis
Another autoimmune disease,
rheumatoid arthritis, leads to damage and painful inflammation
of the cartilage and bone of joints
type 1 diabetes mellitus
the insulin-producing beta cells of the pancreas
are the targets of autoimmune cytotoxic T cells.
MS
The most common chronic neurological disorder in developed countries is
the autoimmune disease multiple sclerosis. In this disease, T cells
infiltrate the central nervous system. The result is destruction
of the myelin sheath that surrounds parts of many neurons
(see Figure 48.12), leading to muscle paralysis through a disruption in neuron function.
Exertion, Stress,
and the Immune System
Moderate
exercise improves immune system
function and significantly reduces the
risk of these infections. In contrast, exercise to the point of exhaustion leads to more frequent infections and to more severe symptoms.
- Similarly, psychological stress has been shown to disrupt immune system regulation by altering the interplay of the hormonal, nervous, and immune systems
immunodeficiency
A disorder in which an immune system response to antigens
is defective or absent is called an immunodeficiency.
inborn immunodeficiency
- An
inborn immunodeficiency results from a genetic or developmental defect in the immune system. - result from defects in the development of various immune system cells or defects in the
production of specific proteins, such as antibodies or the proteins of the complement system. Depending on the specific
genetic defect, either innate or adaptive defenses—or both—
may be impaired. - In severe combined immunodeficiency
(SCID), functional lymphocytes are rare or absent. Lacking
an adaptive immune response, SCID patients are susceptible
to infections, such as pneumonia and meningitis, that can
cause death in infancy. Treatments include bone marrow and
stem cell transplantation
acquired immunodeficiency
An acquired immunodeficiency develops later in life following exposure to chemical
or biological agents. Drugs used to fight autoimmune
diseases or prevent transplant rejection suppress the immune
system, leading to an immunodeficient state.
antigenic variation
Immunological memory is a record of the foreign epitopes an
animal has encountered. If the pathogen that expressed
those epitopes no longer does so, it can reinfect or remain in
a host without triggering the rapid and robust response that
memory cells provide. Such changes in epitope expression,
which are called antigenic variation, are regular events for
some viruses and parasites. The parasite that causes sleeping
sickness (trypanosomiasis) provides one example. By periodically switching at random among 1,000 different versions of
the protein found over its entire surface, this pathogen can
persist in the body without facing an effective adaptive immune response
influenza
Antigenic variation is the major reason the influenza, or
“flu,” virus remains a major public health problem. As it replicates in one human host after another, the human influenza
virus mutates. Because any change that lessens recognition by
the immune system provides a selective advantage, the virus
steadily accumulates such alterations. These changes in the
surface proteins of the influenza virus are the reason that a
new flu vaccine must be manufactured and distributed each
year. Of much greater danger, however, is the fact that the
human virus occasionally exchanges genes with influenza
viruses that infect domesticated animals, such as pigs or
chickens. When this occurs, influenza can take on such a radically different appearance that none of the memory cells in the human population recognize the new strain
latency
After infecting a host, some viruses enter a largely inactive state
called latency. Because such dormant viruses cease making most
viral proteins and typically produce no free virus particles, they
do not trigger an adaptive immune response. Nevertheless, the
viral genome persists in the nuclei of infected cells, either as a
separate small DNA molecule or as a copy integrated into the
host genome. Latency typically persists until conditions arise
that are favorable for viral transmission or unfavorable for host
survival, such as when the host is infected by another pathogen.
Such circumstances trigger the synthesis and release of virus particles that can infect new hosts
herpes simplex viruses
Herpes simplex viruses, which establish themselves in
human sensory neurons, provide a good example of latency.
The type 1 virus causes most oral herpes infections, whereas
the type 2 virus is responsible for most cases of genital herpes. Because sensory neurons express relatively few MHC I
molecules, the infected cells are inefficient at presenting viral
antigens to circulating lymphocytes. Stimuli such as fever,
emotional stress, or menstruation reactivate the virus to reproduce and infect surrounding epithelial tissues.
Once introduced into the body, HIV
infects
helper T cells with high efficiency. To infect these cells, the
virus binds specifically to the CD4 accessory protein (see
Figure 43.16). However, HIV also infects some cell types that
have low levels of CD4, such as macrophages and brain cells.
In the cell, the HIV RNA genome is reverse-transcribed, and the product DNA is integrated into the host cell’s genome
(see Figure 19.8). In this form, the viral genome can direct
production of new virus particles.
Although the body responds to HIV with an immune response sufficient to eliminate most viral infections, some HIV
invariably escapes. One reason HIV persists is
antigenic variation. The virus mutates at a very high rate during replication.
Altered proteins on the surface of some mutated viruses reduce interaction with antibodies and cytotoxic T cells. Such
viruses survive, proliferate, and mutate further. The virus thus
evolves within the body. The continued presence of HIV is
also helped by latency. When the viral DNA integrates into
the chromosome of a host cell but does not produce new
virus proteins or particles, it is shielded from the immune system by the host cell. This inactive, or latent, viral DNA is also
protected from antiviral agents currently used against HIV because they attack only actively replicating viruses.
Over time, an untreated HIV infection
not only avoids the
adaptive immune response but also abolishes it (Figure 43.25).
Viral reproduction and cell death triggered by the virus lead
to loss of helper T cells, impairing both humoral and cellmediated immune responses. The result is a progression to
AIDS, characterized by a susceptibility to infections and cancers that a healthy immune system would usually defeat.
