Transcript activate B cells

Jianzhong Chen, Ph.D.
Institute of Immunology, ZJU
B cell-mediated humoral
immune response
 Humoral immunity is mediated by
antibodies and is the arm of the
adaptive immune response that
functions to neutralize and eliminate
extracellular microbes and microbial
toxins.
 It is more important than cellular
immunity in defending against microbes
with capsules rich in polysaccharides
and lipids, and against polysaccharide
and lipid toxins.
1.
Phases and types of humoral
immune responses
1) Phases
 Antigen recognition phase
 Activation, proliferation and differentiation
phase
 Effector phase
2) Types
 Response to TD-Ag
 Response to TI-Ag
Effector phase
Phases of humoral immune responses
2. Response to TD-Ag
1) B cells recognize TD-Ag
a. BCR directly recognizes B cell epitopes
b. Ig/Ig transfer the first signal
c. Effect of coreceptors (CD21/CD19/CD81)
d. Signalling pathways
BCR directly recognize B cell epitope
The role of coreceptor (CD19/CD21/CD81) in B cell activation
BCR complex-mediated signal transduction in B cells
Functional consequences
of Ig-mediated B cell
activation:
1.
Increase in expression of
costimulators (such as B7)
2.
Increase in expression of
CKRs
3.
Decrease in their
expression of receptors
for chemokines produced
in lymphoid folicles
2) Role of Th cells in humoral
immune response to TD-Ag
 For a protein Ag to stimulate Ab
response, B cells and Th cells specific for
that Ag must come together in lymphoid
organs and interact in a way that
stimulates B cell proliferation and
differentiation.
a. Activation and migration of helper T cells
 Th cells that have been activated to
differentiate into effector cells interact
with antigen-stimulated B cells at the
edges of lymphoid follicles in the
peripheral lymphoid organs.
The interactions of Th cells and B cells in lymphoid tissues.
b. Presentation of Ags by B cells to Th cells
 B cells that bind protein Ags by their BCR
endocytose these Ags, process them in
endosomal vesicles, display MHC IIpeptides for recognition of Th cells.
 B cells and Th cells recognize different
epitopes of the same protein Ag.
Ag presentation by
B cells to Th cells
c. Mechanisms of Th cell-mediated
activation of B cells
 Th cells that recognize Ag presented
by B cells activated B cell by
expressing CD40L and by secreting
cytokines (IL-2, IFN-, IL-4, IL-5, IL-6,
IL-13, etc.).
Mechanisms of Th cell-mediated activation of B cells
Downloaded from: StudentConsult (on 1 June 2006 03:50 PM)
© 2005 Elsevier
d. Th cells stimulate B cells to produce Abs of
different heavy chain classes (isotypes)
 Heavy chain class switching is initiated
by CD40L-mediated signals, and
switching to different classes is
stimulated by different cytokines.
Ig heavy chain class (isotype) switching
e. Affinity maturation in Ab responses
 Affinity maturation is the process by which the
affinity of Abs produced in response to a
protein Ag increases with prolonged and
repeated exposure to that Ag.
 The increase in affinity is due to point
mutations in the V regions, and particularly in
the Ag-binding HVR, of the Abs produced.
 Affinity maturation occurs in the germinal
centers of lymphoid follicles.
Selection of high
affinity B cells in
germinal centers
Downloaded from: StudentConsult (on 1 June 2006 03:50 PM)
© 2005 Elsevier
The anatomy of humoral immune responses
 A fraction of the activated B cells, which are
often the progeny of class-switched highaffinity B cells, do not differentiate into Ab
secretors but instead become memory B
cells.
3. Immune response of B cells to TI-Ag
No Th help，no memory, early effect
* TI-1 (B cell mitogen) activate B cells
- high dose TI-1Ag polyclonally activates B cells
- low dose TI-1Ag specifically activate B cells
* TI-2 activate mature B cells directly
-the repeated epitopes combine with BCR→
BCR cross-linking→produce IgM
The immune response followed by primary
antigenic challenge.
(A) TI-1 Ag
(B) TI-2 Ag
The mechanism of TI-Ag activating B1 cells
4. General features of Ab responses in
vivo
Primary immune response
- longer latent phase;
- smaller peak response (lower Ab titer);
- remaining in the serum at detectable
levels for much shorter periods;
- lower average affinity;
- usually IgM;
Secondary immune response
(The immune response followed by secondary
antigenic challenge)
- shorter latent phase;
- bigger peak response (higher Ab titer);
- remaining in the serum at detectable
levels for much longer periods;
- higher average affinity;
- usually IgG.
Features of primary and secondary antibody responses
5. Functions of antibodies
 Neutralization of microbes and toxins
 Opsonization
 ADCC and other FcR-dependent functions
 Activation of complement
lysis of microbes
opsonization of microbes with C fragments (C3b)
inflammation: C3a, C5a chemoattract neutrophils
The effector functions of antibodies (1)
The effector functions of antibodies (2)
Downloaded from: StudentConsult (on 1 June 2006 04:16 PM)
© 2005 Elsevier
Neutralization By Antiviral Antibodies
Antibody-mediated opsonization and phagocytosis of microbes
Downloaded from: StudentConsult (on 1 June 2006 04:16 PM)
© 2005 Elsevier
Antibody-mediated opsonization and phagocytosis of microbes
Downloaded from: StudentConsult (on 1 June 2006 04:16 PM)
© 2005 Elsevier
ADCC
Effector cells of ADCC
Complement
activation
immunopathology
IgE Antibody Binds
To Mast Cells &
Basophils To Arm
Them For Mediator
Release