CHAPTER 43 NOTES:

THE IMMUNE SYSTEM

Pathogen: a bacterium, fungus, virus, or other disease-causing agent.

Immune system: the body’s defenses, which enables an animal to avoid or limit
may infections. The first line of defense helps prevent pathogens from gaining
entrance to the body; secretions that trap or kill pathogens guard the body’s
entrances and exits, which the linings of exchange surface provides additional
barriers. If a pathogen breaches barrier defenses, the immune system produces
receptor molecules that bind specifically to foreign cells or viruses and activate
defense responses through molecular recognition.

Innate immunity: molecular recognition relies on a small set of receptor proteins

that bind o molecules or structures that are absent from animal bodies but
common to a group of viruses, bacteria, or other pathogens.

Adaptive immunity: molecular recognition relies on 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.

Concept Check 43.1:

CONCEPT 43.1: In innate immunity, recognition and
1. Because pus contains white blood
response rely on traits common to groups of cells, fluid, and cell debris, it
pathogens. indicates an active and at least
partially successful inflammatory
response against invading
INNATE IMMUNITY OF INVERTEBRATES pathogens.

Lysozyme: an enzyme that breaks down bacterial cell walls. It is third third 2. Whereas the ligand for the TLR
immune defense in insects -- the first is the exosletition and the second is the receptor is a foreign molecule, the
chitin that lines the insect intestine. ligand for many signal transduction
pathways is a molecule produced by
Pathogens that breach an insect’s barrier defenses encounters internal immune the organism itself.
defenses -- recognition proteins are produced by immune cells, which bind to
3. Mounting an immune response
components of fungal or bacterial cell walls.
would require recognition of some
molecular feature of the wasp egg
Phagocytosis: the process by which insect immune cells, hemocytes, ingest and
not found in the host. It might be
break down microorganisms. Some hemocytes produce a defense molecule that that only some potential hosts have
helps entrap large pathogens, which others release antimicrobial peptides, which a receptor with the necessary
circulate throughout the body and inactivate or kill fungi and bacteria through specificity.
disrupting their plasma membranes.

If a fungus infects and insect, binding of recognition proteins to the fungal cell
walls activates the Toll transmembrane receptor, which activates production and
secretion of antimicrobial peptides that kill fungal cells.
Many viruses that infect insects have a genome consisting of a single RNA strand
-- when the virus replicates, the RNA strand duplicates. The insect then uses the
Dicer-2 enzyme to cut the viral RNA into 21-nucleotide fragments; the Argo
protein complex binds to a fragment, displacing one of the two strands, and uses
the fragment as a guide to cut the viral mRNA, inactivating it.

INNATE IMMUNITY OF VERTEBRATES

In jawed vertebrates, innate immune defenses coexist with adaptive immunity
defenses.

BARRIER DEFENSES

The barrier defenses of mammals include the mucous membranes that line the
digestive, respiratory, urinary, and reproductive tracts, and skin. In the airway,
ciliated epithelial cells sweep mucus and any entrapped material upward, helping
prevent infection. Saliva, tears, and mucous secretions provide a washing action
that inhibits pathogen colonization, and creates an environment hostile to many
pathogens. Lysozyme in tears, saliva, and mucous secretions destroys the cell
walls of susceptible bacteria, and are very acidic (pH 3 to 5).

CELLULAR INNATE DEFENSES

Toll-like receptor (TLR): a mammalian recognition protein similar to the Toll protein
in insects. Upon recognizing pathogens, TLR proteins produce signals that initiate
responses tuned to the invading microorganism. Each TLR protein binds to
fragments of molecules characteristic of a set of pathogens.

Neutrophils: phagocytic cells in mammals that circulate in the blood and are
attracted by signals from infected tissues -- the neutrophile then engulfs and
destroys the infecting pathogen.

Macrophages: large phagocytic cells that either migrate throughout the body or
reside permanently in organs and tissue where they are likely to encounter
pathogens.

Dendritic cells: cells that mainly populated issues, such as skin, that contact the
environment. They stimulate adaptive immunity against pathogens that they
encounter and engulf.

Natural killer cells: cells that circulate through the body and detect the abnormal
array of surface proteins in some virus-infected and cancerous cells. The natural
killer cells then release chemicals that lead to cell death.

many cellular innate defense in vertebrates involve the lymphatic system, which
distributes lymph throughout the body. Some macrophages reside in lymph
nodes; dendritic cells reside outside the lymphatic system but migrate to lymph
nodes after interacting with pathogens to stimulating adaptive immunity.

ANTIMICROBIAL PEPTIDES AND PROTEINS

In mammals, pathogen recognition triggers produce and release of different

peptides and proteins that attack pathogens or impeded pathogenic reproduction.

Interferons: proteins that provide innate defense by interfering with viral

infections. Virus-infected body cells secrete interferon proteins that induce nearby
uninfected cells to produce substances that inhibit viral replication, thus limiting
the cell-to-cell spread of viruses in the body. Some macrophages secrete a type
of interferon that helps activate macrophages.

Complement system: a system containing roughly 30 protein sint eh blood

plasma that circulate in an inactive state and are activated by substances on the
surface of main pathogens. Activation results in a cascade of biochemical
reactions that can lead to lysis of invading cells. They also contribute to the
inflammatory response.

INFLAMMATORY RESPONSE

Inflammatory response: a set of events triggered by signaling molecules released

upon injury or infection. Activated macrophages discharge cytokines, signaling
molecules that attract neutrophils. Mast cells, immune cells in connective tissue,
release histamine, a signaling molecule that triggers nearby blood vessels to dilate
and become more permeable.

During inflammation, activated complement proteins promote further release of

histamine, attracting more phagocytic cells that carry out additional phagocytosis.
Enhanced blood flow to the site also helps deliver antimicrobial peptides -- this
results in an accumulation of pus, a fluid rich in white blood cells, dead pathogens,
adn debris from damaged tissue.

Systemic inflammatory responses sometimes involve fever. iN response to certain

pathogens, substances released by activated macrophages cause the body’s
thermostat to reset to a higher temperature, which may enhance phagocytosis.

Septic shock: an overwhelming systemic inflammatory response characterized by

very high fever, low blood pressure, and poor blood flow through capillaries.

Chronic inflammation can harm health -- Crohn’s disease and ulcerative colitis are
disorders in which an unregulated inflammatory response disrupts intestinal
function.

EVASION OF INNATE IMMUNITY BY PATHOGENS

Adaptations have evolved in some pathogens that enable them to avoid
destruction by phagocytic cells -- i.e. the outer capsule that surrounds certain
bacteria interfere with molecular recognition and phagocytosis. Some bacteria are
recognized but resist breakdown after being engulfed by a host cell -- rather than
being destroyed, a bacterium can grow and reproduce within host cells. This
causes tuberculosis (TB).
Concept Check 43.2:

1. The transmembrane regions lie

CONCEPT 43.2: In adaptive immunity, receptors within the C regions, which also
 provide pathogen-specific recognition. form the disulfide bridges. In
contrast, the antigen-binding sites
are in the V regions.
Lymphocytes: a type of white blood cells that originate from the stem cells in the
bone marrow. Some migrate from the bone marrow to the thymus, which mature 2. Generating memory cells ensures
into T cells. Lymphocytes that remain and mature in the bone marrow develop as both that a receptor specific for a
B cells. Any given lymphocyte only produces one variety of cell particular epitope will be present and
that there will be more lymphocytes
Antigen: any substance that elicits a B or T cell response. In adaptive immunity, with this specificity than in a host
recognition occurs when a B cell or T cell binds to an antigen via an antigen that had never encountered the
receptor protein, which binds to just one part of one molecule from a particular antigen.
pathogen.
3. If each B cell produced two
different light and heavy chains for
Antigens are usually large foreign molecules, either proteins or polysaccharides.
its antigen receptor, different
Some antigens protrude form the surface of foreign cells or viruses, while others combinations would make four
are released into the extracellular fluid as toxins. different receptors. If any one were
self-reactive, the lymphocyte would
Epitope: the small, accessible portion of an antigen that binds to an antigen be eliminated in the generation of
receptor. A single antigen usually has several epitopes, eah binding a receptor self-tolerance. For this reason, many
with a different specificity. more B cells would be eliminated,
and those that could respond to a
ANTIGEN RECOGNITION BY B CELLS AND ANTIBODIES foreign antigen would be less
effective at doing so due to the
Each B Cell antigen receptor consists of four polypeptide chains: two identical variety of receptors (and antibodies)
heavy chains and two identical light chains linked together by disulfide bridges. they express.

Each chain has a constant (C) region where amino acid sequences vary little
amongst the receptors on different B cells, and a variable (V) region, in which its
amino acid sequence varies extensive from on cell to another. Parts of a heavy-
chain V region and a light-chain V region form an asymmetric binding site of an
antigen.

Binging of a B cell antigen receptor to an antigen is an early step in B cell

activation and leads to formation of cells that secret an antibody, also known as
immunoglobulin (Ig). Antibodies have the same Y-shaped structure as B cell
antigen receptors but lack a membrane anchor.
ANTIGEN RECOGNITION BY T CELLS
The antigen receptor on T cells consists of two polypeptide chains, an alpha chain
and a beta chain, linked by a disulfide bridge. Near the base of the receptor is a
transmembrane region that anchors the molecule in the cell's plasma membrane.
At the outer tip, the variable (V) regions of he chains form a single antigen-binding
site. The remainder of the molecule is made up fo the C regions.

Antigen receptors 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 the major histocompatibility complex
(MHC) molecule.

Display and recognition of protein antigens begin when a pathogen infects a cell
of the animal host or parts of a pathogen are taken in by an immune cell. Enzymes
cleave the antigen into antigen fragments, which binds to an MHC molecule,
transporting the body peptide the cell surface through antigen presentation. If the
cell displaying an antigen fragment encounters a T cell with the right specificity,
the receptor on the the T cell can bind to both the fragment and the MHC
molecule.
B CELL AND T CELL DEVELOPMENT
There are four major characteristics of adaptive immunity:
1. The immense repertoire of lymphocyte sand receptors enables detection
of antigen sn and pathogens never before encountered.
2. Adaptive immunity normally has self-tolerance, the lack of reactivity
against an animal’s own molecules and cells.
3. Cell proliferation triggered by activation greatly increase the number of B
and T cells secreted for an antigen.
4. Immunological memory leads to stronger and and more rapid responses
to previously encountered antigens.

GENERATION OF B CELL AND T CELL DIVERSITY

By combining variable elements, the immune system assembles millions of

different receptors from a very small collection of parts. Every light chain is
encoded by multiple copies of a variable (V) segment, a joining (J) segment, and a
constant (C) segment.
Assembling a functional Ig gene requires rearranging the DNA -- early in B cell
development, the recombinase enzyme complex links one light-chain V gene
segment of one J gene segment. The recombination event eliminates the long
stretch of DNA between the segments, forming a single exon that is part V and
part J.

Recombinase randomly links V segments to J segments. After both a light-chain

and a heavy-chain gene have been rearranged, antigen receptors can be
synthesized. The arranged genes are transcribed, and the transcripts are
processed for translation. The light chain and heavy chain then assemble
together, forming the receptor. Each pair of randomly rearranged heavy and light
chain results in a different antigen-binding site.

ORIGIN OF SELF-TOLERANCE

Because antigen receptor genes are randomly rearranged, some immature

lymphocyte produce receptors specific for epitopes on the organism’s own
molecules. However, as lymphocytes mature in the bone marrow or thymus, their
antigen receptors are tested for self-reactivity -- some B or T cells with self-
attacking receptors are destroyed through apoptosis, while others are typically
rendered nonfunctional.

PROLIFERATION OF B CELLS AND T CELLS

A successful match between an antigen receptor and an epitope initiate servants

Concept Check 43.3:
that activate the lymphocyte bearing the receptor. One activated, a B cell or T cell
undergoes multiple cell divisions, producing clones. 1. A child lacking a thymus would
have no functional T cells. Without
Some cells from the clone become effector cells, mostly short-lived cells that take helper T cells to help activate B cells,
effect immediately -- the effector forms for B cells are plasma cells, which secrete the child would be unable to
antibodies; for T cells, the effect forms are helper T cells and cytotoxic T cells. produce antibodies against
Others become memory cells, long-lived cells that can give rise to effector cells if extracellular bacteria. Furthermore,
the same antigen is encountered later in the animals’ life. without cytotoxic T cells or helper T
cells, the child’s immune system
Clonal selection: the process by which the proliferation of a B cell or T cell into a would be unable to kill virus-infected
clone of cells occurs in response to a specific antigen and to immune cell signals. cells.

2. Since the antigen-binding site is

IMMUNOLOGICAL MEMORY
intact, the antibody fragments could
neutralize viruses and opsonize
Prior exposure to an antigen alters the speed, strength, and duration of the
bacteria.
immune response. The effector cells formed by clones of lymphocytes after an
initial exposure produce a primary immune response, which peaks around 10 - 17 3. If the handler developed immunity
days after initial exposure. If the same antigen is encountered again later, there is to proteins in the antivenin, another
a secondary immune response,a response that is even faster, of greater injection could provoke a severe
magnitude, and more prolonged. immune response.

The secondary immune response relies on the reservoir of T and B memory cells
generated upon initial exposure to an antigen. As the cells are long-lived, they
provide the basis for immunological memory.
 CONCEPT 43.3: Adaptive immunity defends against
infection of body fluids and body cells.
Humoral immune responses: defenses provided by B and T lymphocytes that
occurs in the blood and lymph. In this response, antibodies help neutralize or
eliminate toxins and pathogens in body fluids.

Cell-mediated immune response: specialized T cells destroy infected host cells.

HELPER T CELLS: ACTIVATING ADAPTIVE IMMUNITY

Helper T cell: aa type of T cell that activates humoral and cell-mediated immune
responses. Before this can happen, a foreign molecule must be present that can
bind specifically to he ancient receptor of the helper T cell, and the angin must be
displayed on the surface of an antigen-presenting cell, which can be a dendritic
cell, macrophage, or B cell.

Most body cells have only class I MHC molecules, but antigen-presenting cells
have class I and class II MHC molecules -- class II MHC molecules provide a
molecular signature by which an antigen-presenting cell is recognized.

An antigen-presenting cell engulfs a

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

B CELLS AND ANTIBODIES: A RESPONSE TO EXTRACELLULAR

PATHOGENS
ACTIVATION OF B CELLS

After an antigen-presenting cell engulfs and degrades a pathogen, it displays an

antigen fragment complexed with a class II MHC molecule; a helper T cell is
activated with the aid of cytokines secreted from the antigen-presenting cell.
Stimulated by the helper T cell and cytokines, teh B cell proliferates and
differentiates into memory B cells and antibody-secreting plasma cells.

B cell activation leads to a robust humoral immune response: a single activated B

cell gives rise to thousands of identical plasma cells, which begin secreting
antibodies.

ANTIBODY FUNCTION

Neutralization: the process in which antibodies bind to proteins on the surface of

a virus. The bound antibodies prevent infection of a host cell, neutralizing the
various.

Opsonization: antibodies that are bound to antigens on bacteria do not block

infection, but present a readily recognized structure for macrophages or
neutrophils, promoting phagocytosis. As each antibody has two antigen-binding
sites, antibodies can also facilitate phagocytosis by linking bacterial cells into
aggregates.

When antibodies facilitate phagocytosis, they also help fine-tune the humoral
immune response -- phagocytosis enables macrophage and dendritic cells to
present antigens to and stimulate helper T cells, which stimulate B cells. This
positive feedback contributes to a coordinated, effective response to infection.
Antibodies sometimes work together with th proteins of the complement system
-- binding of a complement protein to an antigen-antibody complex on a foreign
cell triggers the generation of membrane attack complex that forms a pore in the
membrane of the cells. Ions and water then rush into the cell, causing it to lyse.

B cells can express five types of immunoglobulin: IgA, IgD, IgE, IgG, and IgM. Each
class has an identical antigen-binding specificity but a distinct heavy-chain C
region. The B cell antigen receptor, igD, is exclusively membrane bound.

CYTOTOXIC T CELLS: A RESPONSE TO INFECTED HOST CELLS

Cytotoxic T cells: T cells that use toxic 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 interaction with an
antigen-presenting cell.

The targeted destruction of an infected host cell by a cytotoxic T cell involved the
secretion of proteins that disrupt membrane integrity and trigger cell death.

IMMUNIZATION
Immunization: the use of antigens artificially introduced into the body to generate
an adaptive immune response and memory cell formation.

Vaccination programs have been successful against many infectious diseases; in

industrialized, routine immunization has eradicated polio and measles. However, a
decrease in vaccination rates can lead to new epidemics.

ACTIVE AND PASSIVE IMMUNITY Concept Check 43.4:

1. Myasthenia gravis is considered

Active immunity: the defenses that arise when a pathogen infection or
immunization prompts an immune response. an autoimmune disease because
the immune system produces
Passive immunity: the IgG antibodies in the blood of a pregnant female cross the antibodies against self molecules
placenta to her fetus -- the antibodies in the recipient are produced by another (certain receptors on muscle cells).
individual. As passive immunity does not involve the recipient’s B and T cells, it
2. A person with a cold is likely to
persists only as long as the transferred antibodies last.
produce oral and nasal secretions
that facilitate viral transfer. In
ANTIBODIES AS TOOLS addition, since sickness can cause
incapacitation or death, a virus that
Monoclonal antibodies: antibodies that are prepared form a single clone of B cells is programmed to exit the host when
grown in culture. Monoclonal antibodies are identical and specific for the same there is a physiological stress has
epitope on an antigen. the opportunity to find a new host at
a time when the current host may
Home pregnancy test kits use monoclonal antibodies to detect hCG, which is cease to function.
produced as soon as an embryo implants in the uterus.
3. A person with a macrophage
To identify the every virus a person has encountered through infection or deficiency would have frequent
vaccination, researchers use a single drop of blood, and infect it with a set of infections. The causes would be
nearly 100,000 bacteriophages. poor innate responses, due to
diminished phagocytosis and
inflammation, and poor adaptive
IMMUNE REJECTION responses, due to the lack of
macrophages to present antigens to
Like pathogens, cells form another person can be recognized as foreign and
helper T cells.
attacked by immune defenses. MHC molecules are a primary cause of rejection --
as the sets of MHC proteins on cell surfaces are likely to differ between any two
people, such differences can stimulate an immune response in the recipient of a
graft or transplant, causing rejection.

BLOOD GROUPS

In blood transfusions, the recipient's immune system can recognize

carbohydrates on the surface of blood cells as foreign, triggering an immediate
and devastating reaction. Therefore, the donor and recipient must have the same
type of blood (A, B, AB, or O), which represent the types of carbohydrates found
on cell surfaces.

CONCEPT 43.4: Disruptions in immune system

function can elicit or exacerbate disease.
EXAGGERATED, SELF-DIRECTED, AND DIMINISHED IMMUNE
RESPONSES
ALLERGIES

Allergies: exaggerated responses to certain antigens called allergens. The most

common allergies involve antibodies of the IgE class.

An acute allergic response can lead to anaphylactic shock -- inflammatory

chemicals released from immune cells trigger constriction of bronchioles and
sudden dilation of peripheral blood vessels, causing a precipitous drop in blood
pressure.

AUTOIMMUNE DISEASES

Autoimmune disease: a condition in which the immune system is active against

particular molecules of the body. In systemic lupus erythematosus (lupus), the
immune system generates antibodies against histones (proteins found in
chromatin) and DNA released by the normal breakdown of body cells.

Rheumatoid arthritis: damdaming and painful inflammation of the cartilage and

bone in joints -- arthritis is an autoimmune disease and strikes women more often
than men.

Regulatory T cells (Tregs); specialized T cells that help modulate immune system
activity and prevent response to self-antigens.

IMMUNODEFICIENCY DISEASES

Immunodeficiency: a disorder in which an immune system response to antigens is

defective or absent.

Inborn immunodeficiency: results form a genetic or developmental defect in the

production of immune system cells or of specific proteins, such as antibodies or
the proteins of the complement system.In SCID (severe combined
immunodeficiency), functional lymphocytes are rare or absent.

Acquired immunodeficiency: caused by exposure to chemicals or biological

agents. drugs used to fight autoimmune diseases or prevent transplant rejection
suppress the immune system, leading to an immunodeficient state -- one
example is Hodgkin’s disease, which damages the lymphatic system.

EVOLUTIONARY ADAPTATION OF PATHOGENS THAT UNDERLIE

IMMUNE SYSTEM AVOIDANCE
ANTIGENIC VARIATION

Immunological memory is a record of the foreign epitopes an animal has

encountered; therefore, 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. This process is called antigenic variation.

LATENCY

Latency: a largely inactive state of viruses in which the production of most viral
proteins and free viruses cease -- therefore, latent viruses to not trigger an
adaptive immune response. One example is the herpes simplex viruses, which
can cause oral herpes infections (Type 1) or genital herpes (Type 2).

ATTACK ON THE IMMUNE SYSTEM: HIV

Human immunodeficiency virus (HIV): the pathogen that causes AIDS. Once
introduced to the body, HIV infects helper T cells by binding specifically to the
CD4 accessory protein. Inside cells, the HIV RNA genome is reverse-transcribed,
and the product DNA is integrated into the host cell’s genome. Therefore, the girl
genome can direct the production of new viruses.

HIV persits due to its very high mutation rate -- altered proteins on the surface of
some mutated viruses reduce interaction with antibodies and cytotoxic T cells.
The continued presence of HIV is also helped by latency while the viral DNA is
integrated in the host cell’s genome; the latent DNA is shielded form the immune
system as wella s from antiviral agents currently used against HIV.

Acquired immunodeficiency syndrome (AIDS): an impairment in immune

responses that leaves the body susceptible to infections nd cancers that a
healthy immune system would usually defeat. This results when viral replication
and cell death triggered by HIV lead to the loss of helper T cells.

CHAPTER 43 REVIEW QUESTIONS

1. (B) Activation of natural killer cells is not part of insect immunity.

2. An epitope associates with (C) variable regions of a heavy chain and light chain combined on an antigen receptor or
antibody.

3. (C) B cells secrete antibodies against a pathogen; cytotoxic T cells kill pathogen-infected host cells.

4. (B) A lymphocyte does not have receptors for multiple different antigens.

5. (B) The set of MHC molecules produced should be the same in identical twins.

6. Vaccination increases the number of (B) lymphocytes with receptors that can bind to the pathogen.

7. (C) Producing proteins very similar to those of other viruses would not help the virus avoid triggering an adaptive
immune response.