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Ch. 33: The Immune System
Phagocytic White Blood Cells
1) Neutrophils = WBCs that can leave the blood-stream and phagocytize bacteria in tissues
2) Eosinophils = can be phagocytic, but often attack and kill animal parasites (like worms)
3) Macrophages = WBCs found in all sorts of tissues
4) Dendritic Cells = WBCs found in skin

Both engulf pathogens and digest them

Then travel to lymph nodes to stimulate T cells
5) Natural Killer (NK) Cells = lymphocytes that kill virus-infected and cancer cells

Produce cytokines = promote adaptive immunity

Look for cells that lack MHC-1 (Major Histocompatibility Complex I) markers
on their cell surface

Induce these cells to undergo apoptosis
Protective Proteins
1) complement = collection of several blood plasma proteins that “complement” immune
responses

Always present in blood plasma, but must be activated to work

Three functions:
o Enhanced inflammation (amplify it by binding to mast cells)
o Increased phagocytosis = tag cells to be destroyed with additional markers
that make them easier to locate
o Membrane Attack Complexes = some join to form complexes that
produces holes in the surface of some bacteria and viruses

Fluids and salts enter to the point that it bursts
2) Interferons

All are cytokines = proteins that affect the behavior of other cells

Made by viral-infected cells

Bind to receptors of non-infected cells, causing them to produce substances that
slow cellular metabolism and interfere with viral replication
ACQUIRED IMMUNITY: The 2nd Line of Defense
The body must be able to distinguish “self” from “non-self” in order to defend itself against
pathogens
Lymphocytes provide the specificity and diversity of the immune system.
lymphocytes = key cells of acquired (active) immunity

As macrophages and dendritic cells phagocytize microbes, they secrete certain cytokines
that help activate lymphocytes and other cells of the immune system.
o Thus the innate and acquired defenses interact and cooperate with each other.
Antigen = Any foreign molecule that is recognized by and elicits a response from lymphocytes

Most antigens are large molecules such as proteins or polysaccharides, usually attached
to the surface of pathogens or transplanted cells.
Epitope = a small portion of an antigen that a lymphocyte actually recognizes and binds to
Two main types of lymphocytes: B lymphocytes (B cells) and T lymphocytes (T cells).

Both types of lymphocytes circulate throughout the blood and lymph and are
concentrated in the spleen, lymph nodes, and other lymphatic tissue.

Both originate from the bone marrow but B cells mature there, while T cells move to the
Thymus to mature

B and T cells recognize antigens by means of antigen-specific receptors embedded in
their plasma membranes.

The receptors on B cells recognize intact antigens, the receptors on T cells recognize
small fragments of antigens that are bound to normal cell-surface proteins called MHC
molecules.
The Major Histocompatibility Complex (MHC)
Two Classes:

MHC-1 molecules
o Found on almost all nucleated cells of the body
o Used to help immune cells recognize that they are part of “self”
o Any cell that becomes infected or cancerous can display peptide antigens on its
MHC-1 molecules  signals that it is infected and needs to be destroyed
o MHC-1 molecules displaying bound peptide antigens are recognized cytotoxic T
cells  kill infected cells

MHC-2 molecules
o Made by dendritic cells, macrophages, and B cells.
o In these cells, class II MHC molecules bind peptides from foreign materials that
have been internalized and fragmented by phagocytosis.
For each species, there are numerous different alleles for each class I and class II MHC gene,
producing the most polymorphic proteins known.
o As a result of the large number of different alleles in the human population, most of us
are heterozygous for every one of our MHC genes.
o Unique to each individual that marks body cells as “self.”
Lymphocyte development allows the immune system that distinguishes self from nonself.
The variable regions at the tip of each antigen receptor chain, which form the antigen-binding
site, account for the diversity of lymphocytes.
o The variability of these regions is enormous.
o Each person has as many as a million different B cells and 10 million different T cells,
each with a specific antigen-binding ability.
o mRNA splicing differs from one to the next, resulting in different antigen
receptors
o As B and T cells mature, their antigen receptors are tested for potential self-reactivity.
o Lymphocytes bearing receptors specific for molecules of the body are either
destroyed by apoptosis or rendered nonfunctional.
o Failure to do this can lead to autoimmune diseases such as multiple sclerosis.
THE IMMUNE RESPONSE
o Clonal Selection Selection = when a mature lymphocyte encounters and binds a specific
antigen, leading to its activation, proliferation, and differentiation
o One clone consists of a large number of effector cells =short-lived cells that combat the
same antigen.
o The other clone consists of memory cells = long-lived cells bearing receptors for the
same antigen.
o The effector cells are involved in the primary response to infection

Takes 10-17 days to fully respond to and eliminate the pathogen
o The memory cells are involved in any secondary immune responses

Upon a 2nd exposure to the same pathogen, these are quick to respond (2-7
days) and you may never even feel ill
o The immune system can mount two types of responses to antigens: a humoral response
and a cell-mediated response.
HUMORAL IMMUNE RESPONSE
Humoral immunity involves B cell activation and clonal selection and results in the
production of antibodies that circulate in the blood plasma and lymph.
When an antigen first binds to a B cell receptor (BCR), the cell takes in a few of the foreign
molecules by receptor-mediated endocytosis.
o The B cells to begin the process of clonal selection = when the best match between a
specific B cell’s receptor and the antigen is found
o cytokines from helper T cells stimulate the B cells to differentiate
o These B cells are selected and then proliferate, forming two kinds of clones:
o plasma Cells = secrete antibodies (their receptors) into the bloodstream.

Circulating antibodies defend mainly against free bacteria, toxins, and
viruses in the body fluids by binding to them and:


Preventing them from attaching to and entering any new cells

tagging them for quicker macrophage destruction
Each plasma cell is estimated to secrete about 2,000 antibody molecules
per second over the cell’s 4- to 5-day life span.
o Memory Cells = stored B cells that can quickly spring into action upon a 2nd
exposure to a pathogen
Antibodies (a.k.a. Immunoglobulins)

Y-shaped molecules of four polypeptide chains: 2 light and 2 heavy

Each has a constant (C) region that is the same and a variable (R) region that can change
o This region varies due to differential mRNA splicing
o This is where the antigen attaches

Four kinds exist:
o IgG = common in blood

Also in breast milk and able to cross the placenta
o IgM = the other major blood antibody

First kind produced in B-cell responses
o IgA = found in tears, milk, saliva, and mucas
o IgE = involved in allergic reactions (found on eosinophils and mast cells)

Monoclonal Antibodies = produced by cells made from a single plasma cell and all have
antibodies with identical specificity for one antigen
o Cultured in animals (like mice), hybridized with plasma cells, and then extracted
o Used to find specific antigens
o Ex. Pregnancy tests, RSV treatments, cancer detection, and some chemo drugs
CELL-MEDIATED IMMUNE RESPONSE
T cells have a T-Cell Receptor (TCR)

Will only attach to an antigen that is displayed on an MHC on another cell.
Two types of T cells are involved:

Helper T Cells (TH) = regulate adaptive immunity

Cytotoxic T Cells (TC) = attack and kill virus-infected cells and cancer cells
Helper T Cells

Helper T lymphocytes function in both humoral and cell-mediated immunity.

After phagocytizing a pathogen into fragments, Antigen-Presenting Cells (APC’s) travel
to the lymph nodes or spleen, where TH, TC, and B cells congregate

The APC displays a fragment of the pathogen on its MHC-2 protein

When a helper T cell recognizes an MHC-2 molecule-antigen complex on an APC, the
helper T cell proliferates and differentiates into a clone of activated helper T cells and
memory helper T cells.

The activated helper T cells secrete several different cytokines that stimulate other
lymphocytes, thereby promoting both cell-mediated and humoral responses.
o Increase the activity of TC cells, macrophages, NK cells, and B cells
Cytotoxic T Cells

Antigen-activated cytotoxic T lymphocytes kill cancer cells and cells infected by viruses
and other intracellular pathogens.

Cytotoxic T Cells only respond to fragments of pathogens displayed on MHC-1
molecules

After a cytotoxic T cell is activated by this contact with MHC-1 complexes on an
infected cell, the activated TC cell differentiates into an active killer cell, which kills its
target cell—the antigen-presenting cell—primarily by secreting perforin and enzymes
that act on the infected cell.
o Causes the cell to go through apoptosis
o The death of the infected cell not only deprives the pathogen of a place to
reproduce, but also exposes it to circulating antibodies, which mark it for
disposal.

Once activated, cytotoxic T cells kill other cells infected with the same pathogen.

In the same way, cytotoxic T cells defend against cancer cells.
o Because tumor cells carry distinctive molecules not found on normal cells, they
are identified as foreign by the immune system.
o Interestingly, certain cancers and viruses actively reduce the amount of class I
MHC protein on affected cells so that they escape detection by cytotoxic T cells.
o The body has a backup defense in the form of natural killer cells, part of the
nonspecific defenses, which lyse virus-infected and cancer cells.
HIV Infections

Infects and lyses helper T cells

Can insert itself as a provirus

Over time, as its numbers increase, it cripples the immune response by dropping the
helper T cells to a very low number  AIDS

Makes them more susceptible to opportunistic infections, like thrush or shingles