Immunology
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B cells and Antibodies – humoral
T cells and T cell receptors – cell mediated
MHC –HLA DQα is part of the MHC
How MHC, B, and T cells work together
Specific Defenses of the Host
Part 1
acquired or adaptive immunity
i.e., you must be “exposed”
Specific Defenses of the Host
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Called acquired or adaptive immunity.
Although one is born with a general ability to
respond to foreign invasion of the body, the
specific response is developed during a person’s
lifetime.
Immunity, unlike resistance, involves the
production of a specific defensive response against
the particular type of foreign organism or
substance that has invaded the body.
The immune system
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contains two components
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cell-mediated arm (more later)
humoral arm of the immune system
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involves antibodies (also called immunoglobulins) that
are dissolved in blood and lymph
Antibodies are produced by B lymphocytes upon
exposure to a foreign antigen
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Lymphocyte – a type of cell found in the blood
Antigen – anything that can stimulate a specific immune
response
The Structure of a Monomeric
Antibody
Immune system, continued
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B cells have antibodies on their cell surfaces
and the antibodies act as surface receptors for
the antigen.
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Sometimes called B cell receptors
The antibody actually recognizes only a small
region of the antigen called the antigenic
determinant.
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Most antigens have many possible different
antigenic determinants.
Antigenic determinants
Immune system, continued
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Each B cell has many identical antibodies on its
surface. The specificity of each antibody on the
surface of a single B cell is the same.
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In other words, all of the antibodies on the surface of a single
B cell recognize the same antigenic determinant.
After binding of the antigen (specifically, the antigenic
determinant) to the antibody on the B cell surface, the
B cell is stimulated to proliferate and to differentiate
into a plasma B cell that will produce and secrete
antibody of the same specificity that was on the
surface of the B cell.
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These secreted antibodies are dissolved in the plasma of the
blood.
Antigens and B cell receptors
Secretion of antibody following B
lymphocyte stimulation
This picture represents an
overview of multiple steps.
Immune System, continued
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Therefore, the plasma cell produces antibody
that will specifically react with the antigen
(specifically, the antigenic determinant) that
stimulated its production.
Both circulating antibodies and membranebound B cell receptors can recognize and bind
to:
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linear proteins
folded proteins (may recognize non-linear
sequences)
polysaccharides
nucleic acids
Linear Versus Non-linear
Antigenic Determinants
Immune System, continued
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The second arm of the immune system is called
the cell mediated arm of the immune system.
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Involves T lymphocytes that are found in blood and
lymphoid tissues.
T cells, like B cells, have receptors on their cell
surface (called the T cell receptor) that recognize and
bind to antigens (or, more specifically, antigenic
determinants).
The T cell receptor is similar in structure to an
antibody, but is never found secreted into the blood.
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Therefore, cell-mediated
Structure of the T cell receptor
Immune System, continued
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All of the T cell receptors on the surface of a single
T cell recognize the same antigenic determinant.
The T cell receptor is capable of recognizing only
antigenic determinants that are linear pieces of
proteins (peptides). The significance of this will
become clear later in the lecture.
After the T cell receptor is bound by its specific
antigenic determinant, the T cell will be stimulated
to proliferate and differentiate into an effector cell.
There are several different types of effector cells
(helper, supressor, cytotoxic or cytolytic, etc.)
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T cells do not produce antibodies.
Effector T cells
Antigen presenting cell is part of the immune system.
Target cell is any cell in the body that has become infected.
T cells recognize antigens only when bound to MHC molecules.
Mechanisms of the Immune
Response
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Both B and T cells have an antigen
independent and an antigen dependent
phase of maturation.
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Antigen independent maturation
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Pluripotent stems cells in the bone marrow
produce immature B cells that mature to
immunocompetent B cells in the bone marrow.
Immunocompetent B cells have surface
membrane-bound antibodies and are capable
of functioning in an immune reaction.
Mechanisms of the Immune
Response, continued
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Pluripotent stem cells in the bone marrow produce
immature T cells that move to the thymus where they
mature into immunocompetent T cells which have T cell
receptors on their surface that are capable of interacting
with an antigenic determinant in an immune response.
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In the thymus those T cells that respond to self-antigens are
eliminated.
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specific immune response against self-antigens.
http://www.besthealth.com/besthealth/bodyguide/reftext/images/Thymus_spleen.jpghttp://w
ww.besthealth.com/besthealth/bodyguide/reftext/images/Thymus_spleen.jpg
Antigen independent
maturation
Mechanisms of the Immune
Response, continued
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Antigen dependent maturation begins when
antigen (antigenic determinant) binds to
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a B cell receptor (membrane-bound antibody) on the
surface of a B cell or
a T cell receptor on the surface of a T cell.
Binding of the antigen will stimulate a clonal
expansion (proliferation) and differentiation of
the B or T cell.
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Antigen binds only to those B or T cells that are making a
receptor with a good “fit”.
Mechanisms of the Immune
Response, continued
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Antigen dependent maturation of B cells
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B cells will differentiate either into
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plasma cells that will secrete antibody of the same
specificity (recognizes the same antigenic
determinant) that was on the surface of the
original B cell or into
memory B cells.
Antigen dependent maturation
of B cells
B cell clonal expansion
Mechanisms of the Immune
Response, continued
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Antigen dependent maturation of T cells
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T cells will differentiate either into an
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effector cell
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or into a memory cell.
Antigen
dependent
maturation
of T cells
Mechanisms of the Immune
Response, continued
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Memory B or T cells
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Memory cells are responsible for the anamnestic or
secondary response that occurs the next or
subsequent times that the same antigen is
encountered.
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(The immunity has been acquired.)
The anamnestic response is usually much quicker or
stronger than the primary or original response.
Mechanisms of the Immune
Response, continued
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B cells and macrophages often work together with
T cells during an immune response.
When an antigen comes in, B cells and
macrophages will process the antigen and present
pieces of it (antigenic determinants) to a T cell for
stimulation.
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T cell can stimulate another B cell presenting the same
antigen (one of the possibilities during the effector
phase).
Look two slides back.
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What cell surface molecules are involved?
Mechanisms of the Immune Response,
continued (keep track of T, B, and APC cells)
Mechanisms of the Immune
Response, continued
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For many antigens, T cell interaction is required for B cell
stimulation and production of secreted antibodies.
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For “T dependent” antigens, T help (from T helper cells) is
required for B cell stimulation.
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T dependent antigens are all protein antigens that contain some
epitopes recognized by T cells and other epitopes recognized by B
cells.
Stimulation of the B cell in a T-dependent response requires two
signals.
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One signal comes from the binding of the antigen itself to the B cell
receptor (membrane-bound antibody).
The second signal comes from an interaction of the B cell with a T
cell.
Mechanisms of the Immune Response: T-Dependent Antigens
Stimulation of the B cell requires 2 signals.
(More detail on the two signals 2 slides back.)
More steps later.
< 1/100,000 of any
individual’s
immunocompetent
lymphocytes are specific
for any one antigen
Mechanisms of the Immune Response, T Dependent Antigens
Some definitions for previous slide
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IgM, IgG
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Isotype switching –
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Also known as “heavy chain class switching”
A step in B cell maturation
Each of the different heavy chain types is optimal for
eliminating certain types of microbes.
Affinity maturation
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2 of 5 different isotypes, M,G,A,D,E
Isotypes differ with respect to the form of the heavy chain.
A step in B cell maturation that occurs in the germinal
centers of the lymph nodes.
Isotype switching also occurs in cells that undergo affinity
maturation.
Memory cells may be derived either before or after
affinity maturation.
Mechanisms of the Immune
Response, continued
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T helper cells have CD4 on their cell surfaces. The
significance of this will be explained later.
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The T helper cell must be armed by previous
exposure to the same antigen as the B cell which it
helps.
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You will later hear that cytotoxic T lymphocytes have CD8 on
their surfaces.
However, it also “helps” the first such B cell that it
encounters.
The T cell is also restricted in that it can help B cells
produced only by the same individual that produced
the T cells.
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This is because the T cell can recognize the foreign antigen
only in the context of a self-antigen (an MHC complex).
Mechanisms of the Immune
Response, T Dependent Antigens
Note that the B cell surface antibody recognizes one epitope of the antigen while
the helper T cell recognizes another epitope in the context of an MHC Class II
molecule. The antigen is the same (even though it doesn’t look like it), but the
epitopes (or antigenic determinants) differ. In the B cell, some crosslinking of
membrane bound antibodies must occur.
B-T interaction
B-T interaction
Note the role of
CD4!
Based on what
you know about B
cell maturation,
what response
from the B cell to
the cytokine
stimulation would
you expect?
Mechanisms of the Immune
Response, continued
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T help is not required for B cell stimulation in
response to “T independent” antigens.
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T independent antigens are usually in the form of a
repeating subunit like a polysaccharide, lipid, or
nucleic acid, not a protein.
Binding by this type of antigen somehow provides
both signals that are required for B cell stimulation
(by causing extensive cross-linking of the surface
antibodies?)
The outcome from this type of stimulation is clearly
different from that which occurs in T-dependent
stimulation, since with the T-independent stimulation
no memory cells are made. There is no anamnestic
response for T-independent antigens.
T-independent
activation of B
cells
How does the
response
differ from Tdependent
activation?
Compare with
slide #29.
Mechanisms of the Immune
Response, continued
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Cytotoxic T lymphocytes (CTLs) have CD8 on their
surfaces (significance will be described later) and
they act to destroy target cells, including infected
cells, cancer cells, and tissue transplants.
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Cytotoxic T cells are like T helper cells in that, in order to
function, they can only recognize a foreign antigen in the
context of a self-antigen (MHC complex).
The T cell restriction (for both T helper cells and
cytotoxic T cells) involves proteins (sometimes called
antigens) encoded in the Major Histocompatibility
Complex (MHC).