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Lecture 4

Activation of Adaptive Immunity


Overview
 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)

 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
 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

 What are they?


 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)
Major Lymphocyte Populations

B lymphocytes and plasma cells


 T lymphocytes

 Helper/Inducer(CD4)
 Suppressor (CD8)
T Cell Recognition of Antigen
 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
 Class I
 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
 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 Class II CD4+ Helper T


Antigen MHC- Lymphocyte
associated
antigen
B Cell Antigen Recognition

 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 cells (e.g., Langerhan’s cells)


B cells
Properties of
Antigen-
Presenting
Cells
Cellular Cooperation
antigen TH B

Plasma Cells
Antigen presentation to T
and B cells by APC

T cells elaborate cytokines to Antibody secretion by


Antigen presenting cell facilitate B cell proliferation plasma cells
and maturation
Adjuvants
 Freund's Complete Adjuvant (Water-in-oil emulsion)
 mineral oil
 emulsifying agent
 microbial preparation (eg. heat-killed extract of
Mycobacterium tuberculosis)
 aqueous phase containing antigen
 Aluminum Hydroxide Gel
 Microbial Adjuvants
 C. parvum
 BCG
 Peptides and Synthetic Polymers
Effector Mechanisms
 Mechanisms that are used by the immune system to
eliminate pathogens (or other substances) from the
body
 Cellular effector mechanisms
 Activated T cells
 Natural killer cells
 Humoral effector mechanisms (antibody)
 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
 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.