Transcript Lecture 4 Antigen Recognition

Lecture 4
Activation of Adaptive Immunity
Overview
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In order to initiate an immune response antigen must
be recognized.
Antigen recognition depends on detection of antigen
by special receptors.
Antigen recognition depends on cellular cooperation.
Cellular cooperation is controlled by recognition of
MHC-encoded receptors.
Clonal Selection Theory
(F. Macfarlane Burnet)
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Pre-existence of of many different potential
antibody producing cells
Each cell displays surface receptors for specific
antigens
Antigen encounter selects cells
Postulates of the Clonal Selection
Hypothesis
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Each lymphocyte bears a single type of receptor of a unique
specificity
Interaction between a foreign molecule and a lymphocyte
receptor capable of binding that molecule with high affinity leads
to lymphocyte activation
The differentiated effector cells derived from an activated
lymphocyte will bear receptors of identical specificity to those of
the parental cell from which that lymphocyte was derived
Lymphocytes bearing receptors specific for self molecules are
deleted at an early stage in lymphocyte development and are
therefore absent from the repertoire
First a Word About “Cluster of
Differentiation/Designation” (CD) Antigens
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What are they?
Differentiation antigens
 Expressed by cells at distinct stages of
differentiation
 Expressed by cells having different functions
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How are they detected?
Fluorescence-Activated Cell Sorting (FACS)
Major Lymphocyte Populations
B
lymphocytes and plasma cells
 T lymphocytes
 Helper/Inducer
(CD4)
 Suppressor (CD8)
T Cell Recognition of Antigen
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Recognize antigen peptide fragments bound to specialize
cell surface molecules on antigen-presenting cells (APC).
Molecules are encoded by major histocompatibility
complex
Peptides are displayed to T cells as peptide:MHC
complexes
T cell antigen receptors recognize peptide:MHC
complexes
Each MHC molecule can bind numerous different peptides
Two classes of MHC molecules
Major Histocompatibility Complex
(MHC) Gene Products
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Class I
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Antigen is usually endogenous (e.g. viral proteins).
CD8+ cytotoxic T lymphocytes (CTLs) recognize
antigen in association with class I MHC gene product
on APC.
Class II Molecules
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Antigen is usually extracellular.
CD4+ Helper T Lymphocytes recognize antigen in
association with class II MHC gene product on APC.
Cellular Cooperation and
Antigen Recognition
+
APC
Extracellular
Antigen
Class II
MHCassociated
antigen
CD4+ Helper T
Lymphocyte
B Cell Antigen Recognition
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Cell surface immunoglobulin receptor or B-cell
receptor (IgM and IgD)
Antigen contact initiates B-cell activation, clonal
expansion, maturation to plasma cell
Antigen receptor is identical to immunoglobulin
that will ultimately be produced
Antigen Presenting Cells
 Macrophages/monocytes
 Dendritic
B
cells
cells (e.g., Langerhan’s cells)
Properties of
AntigenPresenting
Cells
Cellular Cooperation
antigen
TH
B
Antigen presentation to T
and B cells by APC
Antigen presenting cell
T cells elaborate cytokines to
facilitate B cell proliferation
and maturation
Plasma Cells
Antibody secretion by
plasma cells
Adjuvants
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Freund's Complete Adjuvant (Water-in-oil emulsion)
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Aluminum Hydroxide Gel
Microbial Adjuvants
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mineral oil
emulsifying agent
microbial preparation (eg. heat-killed extract of
Mycobacterium tuberculosis)
aqueous phase containing antigen
C. parvum
BCG
Peptides and Synthetic Polymers
Effector Mechanisms
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Mechanisms that are used by the immune system to
eliminate pathogens (or other substances) from the
body
Cellular effector mechanisms
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Activated T cells
Natural killer cells
Humoral effector mechanisms (antibody)
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Neutralization
Opsonization
Complement activation
Antibody-dependent cell-mediated cytotoxicity (ADCC)
Effector Activity Against Pathogens
Clonal Expansion Following Antigen
Exposure
Virgin lymphocyte pool
PRIMARY RESPONSE
effector cells
memory cell pool
SECONDARY RESPONSE
effector cells
memory cell pool
The Bottom Line
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In order to initiate an immune response
antigen must be recognized.
Antigen recognition depends on detection of
antigen by special receptors.
Antigen recognition depends on cellular
cooperation.
Cellular cooperation is controlled by
recognition of MHC-encoded receptors.
Antigen “drives” the process resulting in
“effector” cells and “memory” cells.