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

Class I

Major Histocompatibility
Complex (MHC) Gene
Products

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
Antigen

Class II
CD4+ Helper T
MHCLymphocyte
associated
antigen

B Cell Antigen Recognition

Cell surface immunoglobulin receptor or Bcell 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
Dendriticcells(e.g.,Langerhanscells)
Bcells

Properties
of AntigenPresenting
Cells

Cellular
Cooperation
antigen

TH

Plasma Cells

Antigen presentation to T
and B cells by APC

Antigen presenting cell

T cells elaborate
cytokines to facilitate B
cell proliferation and
maturation

Antibody secretion
by plasma cells

Adjuvants

Freund'sCompleteAdjuvant(Waterinoilemulsion)

AluminumHydroxideGel
MicrobialAdjuvants

mineraloil
emulsifyingagent
microbialpreparation(eg.heatkilledextractof Mycobacterium
tuberculosis)
aqueousphasecontainingantigen

C.parvum
BCG

PeptidesandSyntheticPolymers

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.