Transcript Lecture 4 Antigen Recognition

Lecture 15
Antigen Recognition
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
What prevents recognition/destruction of self
tissues?
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
Diversity of Lymphocyte Antigen
Receptors
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Variable region of antigen receptor encoded by sets of gene
segments
During lymphocyte development somatic gene
rearrangement create unique combinations of gene
segments
Once recombinant events have occurred, further
rearrangement is prohibited
Receptor specificity of a lymphocyte cannot change
Each lymphocyte bears many copies of the unique receptor
At least 108 different lymphocytes in an individual
Genomic Organization of heavy- and
light-chain segments
Development of the Antibody
Repertoire
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The antibody repertoire is generated during B cell
development by DNA rearrangements that
combine and assemble variable-region gene
segments (somatic diversification theory)
Diversity is enhanced by hypermutation in mature
B cells (germline theory)
Some Comments on Cluster of
Differentiation/Designation (CD) Antigens
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What are they?
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Differentiation antigens
Expressed by cells at distinct stages of
differentiation
Expressed by cells having different
functions
How are they detected?
Fluorescence-Activated Cell Sorting (FACS)
Lymphocyte Populations
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B lymphocytes
Plasma cells
T lymphocytes
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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
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
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.