Chapter15 B cell mediated immune response

1. Chapter15 B cell mediated immune response

2. 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

3. Contents • PartⅠ Immune response of B2 cell to TD-Ag • Part II Rules of humoral immunity • Part Ⅲ Immune response of B1 to cell TI-Ag

4. PartⅠ Immune response of B2 cell to TD-Ag 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

5. B2 cells recognize TD-Ag activate, proliferate, differentiate plasma cells produce Ab

6. 1.B cells recognize antigen • BCR directly recognize the conformational determinant, capture Ag and present Ag signal to Th cells • No APC , no MHC restriction • Specificity

7. linear conformational

8. 2. B cells activation, proliferation and differentiation (1) B cell activation: dual signals • First signal : antigen signal BCR--conformational determinant on the surface of Ag Igα/Igβtransduct first signal CD19/CD21/CD81 (co-receptor) binds to C3d on Ag • Second signal: co-stimulatory signal The CD40 on B cells binds to CD40L on activated T cells

9. CD225 (Leu-13)

10. Endosome

11. Antigen 3. Thcell isactivated andexpressesCD40ligand, Cytokinessecreted B cell B cell B cell B cell B cell B cell T helper cell T helper cell CD40 TCR MHC II 5. B cellactivated 1. Antigenpresentationto Thcell CD28 B7 6. Bcells proliferate, differentiate, secrete Ig CD40 ligand Immunoglobulin receptor 2. B7expressed Cytokine receptor Cytokine

12. 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

16. (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

17. 免疫记忆 免疫记忆

18. cytokines CD4 T cells cytokines Thymus dependent antigen Functions of CK in HI Promote B cell to proliferate and differentiate Determine the types of Abs produced by isotype switch

20. Differentiation of B cell in germinal Center • Some B cells differentiate into plasma cells • Somatic hypermutation of B cells induces affinity maturation of Ab • Some B cells have isotype switch to produce other types of Ig---need help of CKs • Production of memory B cells

22. lymph node

26. IgM switch to IgG

27. IgM switch to IgA

28. 3. Effect Stage ---the function of Ab

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

30. 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.

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

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

33. 5. Participate in hypersensitivity IgE 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

37. Part II Rules of humoral immunity 1. Primary response 2. Secondary response

38. ____________________________________________ • 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 disease On vaccination : To obtain secondary response by more times of vaccination

42. Part III Immune response of B1 cells to TI-Ag Characteristics of TI-Ag: • Repeated B cell epitopes • No participation of T cells • Only humoral immunity • Only produce IgM • No immune memory

43. B1 cells mediated immune response to 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

46. B1 cells mediated immune response to TI-2 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

48. Summary • 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