Chapter15 B cell mediated immune response

B cells mediated immune response

Humoral immunity(HI) or antibody mediated immunity:

The total immunological reaction that B cells recognize antigen, then to be activated, 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

Part Immune response of B2 cell to TD-AgⅠ

Part II Rules of humoral immunity

Part Ⅲ Immune response of B1 to cell TI-Ag

Part Immune response of B2 cell to TD-AgⅠPart Immune response of B2 cell to TD-AgⅠ

Characteristics of TD-Ag:• Possess T cell epitope and B cell epitope• Need Th cells participation• Both CMI and HI• Produce several types of antibodies: IgG

• Produce immune memory

• B2 cells recognize TD-Ag activate, proliferate,

differentiate plasma cells produce Ab

1.1.    B cells recognize antigenB cells recognize antigen

• BCR directly recognize the conformational determinant, capture Ag and present Ag signal to Th cells

• No APC , no MHC restriction

• Specificity

conformationallinear

2. B cells activation, proliferation 2. B cells activation, proliferation and differentiationand differentiation

(1) B cell activation: dual signals • First signal : antigen signal BCR--conformational determinant on the surfa

ce of Ag Igα/Igβtransduct first signal CD19/CD21/CD81 (co-receptor) binds to C3d o

n Ag• Second signal: co-stimulatory signal The CD40 on B cells binds to CD40L on activ

ated T cells

CD225

(Leu-13)

Endosome

CD40

Immunoglobulinreceptor

MHC II

Antigen

Cytokine receptor

Bcell

B7B7B7B7 CD28

TCRTCRTCRTCRT helpercell

1. Antigen presentation toTh cell

2. B7 expressed

Bcell

3. Th cell is activated

and expresses CD40 ligand,

Cytokines secretedCD40

ligand

Cytokine

Bcell

T helpercell

Bcell

Bcell

Bcell

5. B cell activated

6. B cells proliferate, differentiate, secrete Ig

Interaction between Th cell and B cell

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 produce Cks （ IL-4 、 IL-5 、 IL-

6 、 IL-10 、 IL-13 ） which help B cells proliferate and differentiate

(2) B cells proliferate and differentiate------help of Th

• Activated B cells express receptors of cytokines(IL-4R, IL-5R, IL-6R )

• Activated Th2 secrete cytokines IL-4, IL-5,IL-6 to enhance proliferation and differentiation of B cells

• B cells differentiate into plasma cells ( antibody forming cells)---- produce Ab, some activated B cells become memory B cells

免疫记忆免疫记忆

                                                                    

                                               

cytokines

Thymus dependent antigen

CD4 T cells

cytokines

Functions of CK in HI Promote B cell to proliferate and differentiateDetermine the types of Abs produced by isotype switch

Differentiation of B cell in germinal Center

① Some B cells differentiate into plasma cells

② Somatic hypermutation of B cells induces affinity maturation of Ab

③ Some B cells have isotype switch to produce other types of Ig---need help of CKs

④ Production of memory B cells

lymph node

IgM switchIgM switch to IgGto IgG

IgM switch IgM switch to IgAto IgA

    3. Effect Stage3. Effect Stage

---the function of Ab ---the function of Ab

1.   Neutralization: * neutralize microbial toxins and animal venoms * prevent viruses and bacteria from infecting cells

2. ADCC—NK Antibody-coated target cells can be killed by natural killer cells(NK cell) in antibody-dependent cell-mediated cytotoxicity, that is called ADCC.

3.Opsonization – macrophageFc receptors on phagocytes trigger the uptake of antibody-coated bacteria.As a result, this action enhance phagocytosis of the bacterium.

Complement proteins bind to antibodies.Complement proteins bind to antibodies.

4.Activation of complement Complement can be activated to directly lyse bacteria by the presence of Complement can be activated to directly lyse bacteria by the presence of antibodies bound to the bacteria.antibodies bound to the bacteria.

5. Participate in hypersensitivityIgE binds to high-affinity Fc receptors on mast cells and basophils, and leads to the rapid release of granules containing inflammatory mediators into surrounding tissue, cause hypersensitivity

Part II Rules of humoral immunityPart II Rules of humoral immunity

1. Primary response

2. Secondary response

• ____________________________________________

• Primary IR Secondary IR• ____________________________________________• latent phase long short• peak concentration low high• maintaining time short long• Ab type mainly IgM mainly IgG• Ab titer low high• affinity low high• ____________________________________________

Significance:

On diagnosis: IgM is a marker for early diagnosis of infectious diseaseOn vaccination : To obtain secondary response by more times of

vaccination

Part III Immune response of B1 cellPart III Immune response of B1 cells tos to TI-Ag TI-Ag

Characteristics of TI-Ag:

• Repeated B cell epitopes• No participation of T cells • Only humoral immunity• Only produce IgM• No immune memory

• 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

B1 cells mediated immune response to TI-1 Ag:

• Most TI-2 Ags have highly repeated epitope

• Only stimulate mature B1 cells

• Density of epitope is key to TI-2 Ag to activate B cells

• Help macrophage phagocytose and digest extracellular bacteria under antibody of capsule polysaccharide

B1 cells mediated immune response to TI-2 Ag

SummarySummary

Process of Immune response mediated by B2 cell to TD-Ag

Immune response of B1 to cell TI-Ag

Difference of primary HI and secondary HI