chapter 15 b cell mediated immune response. chapter 15 b cells mediated immune response humoral...

Chapter 15 Chapter 15

B cell mediated immune respB cell mediated immune resp

onseonse

Chapter 15 Chapter 15

B cell mediated immune respB cell mediated immune resp

onseonse

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 TD-A

g

PartⅡ Rules of humoral immunity

PartⅢ Immune response of B1 cell to TI-Ag

PartⅣ Signal transduction of T and B cells

PartⅠ Immune response of B2 cell to PartⅠ Immune response of B2 cell to TD-AgTD-Ag

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 PartⅠ Immune response of B2 cell to TD-AgTD-Ag

• B2 cells recognize TD-Ag

activate, proliferate,

differentiate plasma cells produce Ab

Ag

B cells can recognise native antigens directly

YY Y Y YYY

B

Proliferation and antibody production

Cross-linking of surface membrane Ig

Y

B

Y

B Y

B

Y

B

Y

B Y

B

Y

BYY

B

Th

1.1.    B cells recognize B cells recognize antigenantigen

• 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, 2. B cells activation, proliferation and proliferation and differentiationdifferentiation

(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 activa

ted Th cells

BCR complex

Ag

ITAM

Ag

（ BCR ）

ITAM

g

B cell

Activation of Th cells: DCs present peptide-class Ⅱ MHC complex and provide B7 for T cells, Th cells are activated and e

xpress 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.

Second signal: --the help of Th cells to 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 mo

lecule 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) B cells proliferation and differentiation------help of Th cells

• 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 maturationAffinity 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 isotyisotype switchingpe switching or or class switchingclass 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 Ab3. 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

PartPartⅡⅡ Rules of humoral immunity Rules of humoral immunity

1. Primary response

2. Secondary response

Characteristic of primary Ir and secondary Ir

lag phase 　 affinity 　 type maintaining time

primary Ir longer low IgM shorter secondary Ir shorter high IgG longer

Mechanisms?Mechanisms?

Bm/TmBm/Tm

Significance: On diagnosis: IgM is a marker for early

diagnosis of infectious diseaseOn vaccination: To obtain secondary re

sponse by more times of vaccination

PartPartⅢⅢ Immune response of B1 cell Immune response of B1 cell

to TI-Agto TI-Ag

Characteristics of TI-Ag:• Repeat B cell epitope• No T cells participation• Only humoral immunity• Only produce IgM• No immune memory

PartPartⅢⅢ Immune response of B1 cell Immune response of B1 cell

to TI-Agto 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 pro

liferation and differentiation.• Low TI-1 Ag only stimulate B cell clone with s

pecific BCR.• Response of B1 cell to TI-1 Ag earlier than tha

t of B2 cell to TD-Ag.• No Ig isotype swicth, affinity maturation, and

memory B cells.

M

PartPartⅢⅢ Immune response of B1 cell Immune response of B1 cell

to TI-Agto TI-Ag

B1 cells recognize TI-2 Ag :• Most TI-2 Ags belong to cell wall of bacteria a

nd 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 extra

cellular bacteria under antibody of capsule polysaccharide.

PartPartⅢⅢ Immune response of B1 cell Immune response of B1 cell to TI-Agto TI-Ag

Significance:Significance:• Play important role in Play important role in defense against e

xtracellular microbe infection.• Play an important role in Play an important role in defense again

st 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