Download Chapter 11 Immune response(Ir)

Chapter 15
B cell mediated immune
response
Chapter 15 B cells mediated immune response
Humoral immunity(HI) or antibody mediated
immunity:
The total immunological reaction that B cells
recognize antigen, then activate, proliferate,
differentiate into plasma cells and produce Ab.
• B2 cells mediated immune response to TD-Ag
• B1 cells mediated immune response to TI-Ag
Contents
 PartⅠ Immune response of B2 cell to TDAg
 PartⅡ Rules of humoral immunity
 PartⅢ Immune response of B1 cell to TIAg
 PartⅣ Signal transduction of T and B
PartⅠ Immune response of B2 cell to TDAg
Characteristics of TD-Ag:
• Most native Ag
• Protein, large molecules
• Possess T cell epitope and B cell
epitope
• Both CMI and HI
• Need Th cells participation
• Produce several types of antibodies:
IgG
• Produce immune memory
PartⅠ Immune response of B2 cell to TDAg
• B2 cells
recognize TD-
Ag
Ag proliferate,
activate,
differentiate
plasma
cells
produce Ab
B
Y
Y
Y
Y
Y
Y
Y
Cross-linking of
surface membrane Ig
B B
B B BB
B B
YYY Y
Y Y Y Y
Th
Proliferation and
antibody production
B cells can recognise native antigens directly
1. B cells recognize
antigen
• BCRs directly recognize the epitope
on the surface of Ag
• No APC , no MHC restriction
• Capture Ag by BCR, present Ag signal
to T cells
2. B cells activation,
proliferation and
differentiation
(1) B cell activation: dual signals
• First signal: antigen signal
BCR-- determinant on the surface of Ag
Igα/Igβtransduct the first signal
CD19/CD21/CD81 (co-receptor) binds to
C3dg on Ag
• Second signal: co-stimulatory signal
The CD40 on B cells binds to CD40L on
activated Th cells
Ag
Ag
（BCR）
BCR complex
ITAM
ITAM
g
B cell
Second signal: --the help of Th
cells to Activation
B cells of Th cells:
DCs present peptide-class Ⅱ MHC complex
and provide B7 for T cells, Th cells are activated
and express CD40L.
Th cells provide co-stimulatory signal for B
cells:
TCRs on activated Th cells recognize antigen
peptide-class Ⅱ MHC complex presented on B
cells, and CD40L on T cells bind to CD40 on B
cells which provide co-stimulatory signal for B
cells.
Dendritic cell
Interaction between Th cells and B
cells
B cells act on Th cells:
• B cells present Ag to Th cells.
• B cells provide B7 for Th cells.
Th cells act on B cells:
• Activated Th cells provide co-stimulatory
molecule for B cells: CD40L- CD40.
• Activated Th cells secrete Cks（IL-4、IL-5、
IL-6、IL-10、IL-13）which help B cells
proliferate and differentiate.
①
②
(2)
cells
proliferation
differentiation
------help of Th cells
•
•
•
B
and
Activated B cells express receptors of
cytokines such as IL-4R, IL-5R.
Activated Th2 cells secrete cytokines such
as IL-4, IL-5 to enhance proliferation and
differentiation of B cells.
B cells differentiate into plasma cells
(antibody forming cells)----produce Ab,
partial into memory B cells.
免疫记忆
Differentiation of B cells in germinal
Center
•
•
•
•
During proliferation and differentiation,
Somatic hypermutation of B cells induces
affinity maturation of Ab.
Some B cells differentiate to the plasma
cells which produce IgM.
Some B cells have an isotype switch to
produce other types of Ig.
Production of memory B cells.
• Affinity maturation refers to the
increase in the affinity for the
specific antigen of the antibodies
produced during the course of a
humoral immune response with the
help of Th cells. Affinity maturation
is the result of somatic
hypermutation of Ig genes.
Plasma cells are antibody
factories;
Also called antibody
forming cells;
Produce huge numbers of
antibodies:2000/second
• The first antibodies produced in a
humoral immune response are IgM,
but activated B cells subsequently
undergo isotype switching or class
switching to secrete antibodies of
different isotypes: IgG, IgA, and IgE.
Isotype switching does not affect
antibody specificity significantly.
3. Stage of effect----the function
of Ab
•
•
•
•
•
Neutralization
Activate complement system
ADCC — NK, macrophage, neutrophil
Opsonization — macrophage
Type Ⅰ hypersensitivity
Neutralization Opsonization
Activate
complement
system
ADCC
PartⅡ Rules of humoral immunity
1. Primary response
2. Secondary response
Characteristic of primary Ir and secondary
Ir
time
lag phase
primary Ir
longer
shorter
secondary Ir shorter
longer
affinity
low
high
type maintaining
IgM
IgG
Mechanisms?
Bm/Tm
Significance:
On diagnosis: IgM is a marker for
early diagnosis of infectious disease
On vaccination: To obtain secondary
response by more times of
vaccination
PartⅢ Immune response of B1 cell to
TI-Ag
Characteristics of TI-Ag:
•
•
•
•
•
Repeat B cell epitope
No T cells participation
Only humoral immunity
Only produce IgM
No immune memory
PartⅢ Immune response of B1 cell to
TI-Ag
B1 cells recognize TI-1 Ag:
• TI-1 Ag usually called B cell mitogen.
• High TI-1 Ag can induce polyclonal B cells
proliferation and differentiation.
• Low TI-1 Ag only stimulate B cell clone with
specific BCR.
• Response of B1 cell to TI-1 Ag earlier than
that of B2 cell to TD-Ag.
• No Ig isotype swicth, affinity maturation,
and memory B cells.
M
PartⅢ Immune response of B1 cell to
TI-Ag
B1 cells recognize TI-2 Ag :
• Most TI-2 Ags belong to cell wall of
bacteria and capsule polysaccharide with
high repeat structure.
• Density of epitope is key to TI-2 Ag
activating B cells.
• Only stimulate mature B1 cells.
• Help macrophage phagocyte and digest
extracellular bacteria under antibody of
capsule polysaccharide.
PartⅢ Immune response of B1 cell to
TI-Ag
Significance:
• Play important role in defense against
extracellular microbe infection.
• Play an important role in defense
against bacteria with capsule
polysaccharide.
PartⅣ signal transduction of T
and B cell activation
TCR recognition and linkage
Activation of PTK( p56lck, p59fyn, ZAP-70)
Signal transduction in the cell
Activation of transcription factor
APC