1. Humoral Immune response
Jianzhong Chen, Ph.D.
Institute of Immunology, ZJU

2. 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.

3. Phases and types of humoral immune responses
Antigen recognition phase
Activation, proliferation and differentiation phase
Effector phase
2) Types
Response to TD-Ag
Response to TI-Ag
* 主要针对细胞外病原体
* TD-Ag和TI-Ag

4. Phases of humoral immune responses
Effector phase
Phases of humoral immune responses

5. 2. Response to TD-Ag

6. a. BCR directly recognizes B cell epitopes
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

7. BCR directly recognize B cell epitope
复习B表位和T表位
BCR直接识别B表位，为单识别，不受MHC的限制性。
BCR directly recognize B cell epitope

8. The role of coreceptor (CD19/CD21/CD81) in B cell activation

9. BCR complex-mediated signal transduction in B cells

10. Functional consequences of Ig-mediated B cell activation:
Increase in expression of costimulators (such as B7)
Increase in expression of CKRs
Decrease in their expression of receptors for chemokines produced in lymphoid folicles

11. 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.

12. 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.

13. The interactions of Th cells and B cells in lymphoid tissues.

14. 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 II-peptides for recognition of Th cells.
B cells and Th cells recognize different epitopes of the same protein Ag.

15. Ag presentation by B cells to Th cells

16. 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.).

17. Mechanisms of Th cell-mediated activation of B cells
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18. 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.

19. Ig heavy chain class (isotype) switching

20. 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.

21. Selection of high affinity B cells in germinal centers
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22. The anatomy of humoral immune responses

23. A fraction of the activated B cells, which are often the progeny of class-switched high-affinity B cells, do not differentiate into Ab secretors but instead become memory B cells.

24. 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

25. The mechanism of TI-Ag activating B1 cells
The immune response followed by primary antigenic challenge.
(A) TI-1 Ag
(B) TI-2 Ag
The mechanism of TI-Ag activating B1 cells

26. 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;

27. 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.

28. Features of primary and secondary antibody responses

29. 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

30. The effector functions of antibodies (1)

31. The effector functions of antibodies (2)
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32. Neutralization By Antiviral Antibodies

33. Antibody-mediated opsonization and phagocytosis of microbes
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34. Antibody-mediated opsonization and phagocytosis of microbes
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35. ADCC

36. Effector cells of ADCC
ADCC can be mediated by NK cells, macrophages, neutrophils and eosinophils.

37. Complement activation

38. immunopathology IgE Antibody Binds To Mast Cells & Basophils To Arm Them For Mediator Release