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Specific Defenses of the Host
Part 1
(acquired or adaptive immunity)
Specific Defenses of the Host
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Also called acquired or adaptive immunity.
Although one is born with the 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 foreign organisms or substances
that have invaded the body.
The immune system
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contains two components
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the 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 (an antigen
is 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 surface and
the antibody acts as a surface receptor for the
antigen.
The antibody actually recognizes only a small
region of the antigen called the antigenic
determinant.
Each antigen has many 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.
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 produce
and secrete antibody of the same specificity
that was on the surface of the B cell.
Antigens and B cell receptors
Secretion of antibody following B
lymphocyte stimulation
B cell clonal expansion
Immune System, continued
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Therefore, the B cells produces antibody that
will specifically react with the antigen
(specifically, the antigenic determinant) that
stimulated its production.
Antibodies (or B cell receptors) can recognize
and bind to linear proteins, folded proteins
(may recognize non-linear sequences),
polysaccharides, or 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.
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 binding of the T cell receptor with its specific
antigenic determinant, the T cell will be stimulated to
differentiate into an effector cell.
There are several different types of effector cells (helper,
supressor, cytotoxic, etc.)
Effector T cells
T4 activation
T4 proliferation
T8 activation
Killing by cytotoxic T cell
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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Pluripotential stems cells in the bone marrow
produce immature B cells that mature to
immunocompetent B cells in the bone marrow.
Immunocompetent B cells have antibody
receptors on their surface and are capable of
functioning in an immune reaction.
Mechanisms of the Immune
Response, continued
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Plurpotential 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.
In the thymus the T cells learn to distinguish
between self-antigens and non-self antigens.
Thus, the immune system does not normally
produce a specific immune response against
self-antigens.
Antigen independent
maturation
Mechanisms of the Immune
Response, continued
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Antigen dependent maturation
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Antigen dependent maturation begins when antigen
(antigenic determinant) binds to an antibody receptor on
the surface of a B cell or the T cell receptor on the
surface of a T cell.
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Binding of the antigen will stimulate a clonal expansion
(proliferation) and differentiation of the B or T cell.
B cells will differentiate either into 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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T cells will differentiate either into an effector cell
(helper, supressor, cytotoxic, etc) or into a memory
cell.
Memory cells are responsible for the anamnestic or
secondary response that occurs the next or
subsequent times that the same antigen is
encountered.
The anamnestic response is usually much quicker or
stronger than the primary or original response.
Antigen dependent maturation
of T cells
Mechanisms of the Immune
Response, continued
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B cells often work together with T cells and
macrophages 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 the B or T cell for
stimulation.
Mechanisms of the Immune Response,
continued
Mechanisms of the Immune
Response, continued
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Many antigens require T cell interaction for B cell
stimulation and production of secreted
antibodies.
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T dependent antigens require T help (T helper cells)
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 requires two signals.
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One signal comes from the binding of the antigen itself to
the B cell receptor (antibody).
The second signal comes from an interaction of the B cell
with a T cell.
Mechanisms of the Immune Response, T Dependent Antigens
< 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. The T
helper cell must be armed by previous exposure to
the same antigen as the B cell which it helps.
The T cell is restricted in that it can only help B cells
produced by the same individual that produced the T
cells. This is because the T cell can only recognize
the foreign antigen 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 differ. In the B cell, some crosslinking of membrane bound antibodies
must occur.
B-T interaction
B-T interaction
Mechanisms of the Immune
Response, continued
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T independent antigens don’t require T help for B cell
stimulation.
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T independent antigens are usually in the form of a
repeating subunit like a polysaccharide, lipid, or nucleic acid.
Binding by this type of antigen somehow provides both
signals that are required for B cell stimulation (by causing
extensive cross-linking 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 #32.
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).