1. Humoral Ir mediated by B cells
Chapter 12
Humoral Ir mediated by B cells

2. Major content Concept Response to TD-Ag
Characteristics of primary and secondary Ir
Response to TI-Ag
Effect of B cell response

3. 体液免疫应答 (humoral immunity)
B cells encounter specific Ag, activate ,proliferate and differentiate to plasma cells，produce Abs, eliminate Ags.
Ab exist in blood, important effector.
* 主要针对细胞外病原体
* TD-Ag和TI-Ag

4. Classification B cells Respond to TD-Ag （protein)
B cells Respond to TI-Ag (Glucose and Glylipid）

5. B cells response to TD-Ag

6. B cell antigen receptor complex

7. BCR direct 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。

8. B cell and Th cell recognize different epitope on the same Ag
载体效应

9. BCR recognize Ag and activation of B cell
信号1
* B细胞特异性结合抗原，向B细胞传递抗原刺激信号；
* 通过BCR摄取抗原，并将抗原降解为肽段，形成抗原肽-MHC-II类分子复
合物，供抗原特异性Th细胞识别；

10. B cells response to TD-Ag
* B cells recognition to TD Ag
* B cells activation, proliferation and differentiation
* Primary and secondary response
* Effect of B cell response

11. B cell activation （一）active siganl 1 (Ag)
* BCR specific bind epitope on B cell；
*co-receptor：CD21/CD19/CD81 bind C3d linked with Ag；
* Igα/Igβ：signal transduct；
（二） active siganl2 (co-stimulatory molecule)
*activation of naive Th：APC（DC) present double siganls and CK to naive CD4+T.
develop to effective Th；
* B cell present Ag：B cell take in Ag via BCR，process it，formation of peptide-MHC complex，present to Th；
* Effective Th combines with B cell specifically：TCR recognize Ag presented by B；
*Co-stimulatory sgnal：CD40L(on active T) bind CD40(on B cell)；
（三）CKs
IL-1/APC、 IL-4/Th promote activation of B cell.

12. BCR and co-receptor complex
经典途径、替代途径和MBL途径

13. This slid show us comparison the molecules involved in antigen recognition by T cells and B cells..
Antigen receptor: T cell is TCR and B cell is BCR
Recognition:
- Antigen recognition of T cell is dual recognition, while antigen recognition by B cell is single recognition. TCR recognizes epitope presented by MHC, so both peptide and self MHC molecule
-BCR directly recognizes epitope on tne surface of native antigen.
Coreceptor:
- For T cell is CD4 and CD8
- For B cell is CD19/CD21/CD81 complex
Signal transduction molecules
- for T cell is CD3
-for B cell is Ig-alpha and Ig-beta.

14. Interaction of T and B cells
Th细胞和B 细胞间相互作用
Interaction of T and B cells

15. Bidirectional T cell -B cell interaction

17. Tow times of recognition
CD B7.1/2
SIGNAL 2 DC Th
Processing
SIGNAL 1
naive
effector
CD B7.1/2

18. Th help B cell activating, proliferating and differentiating

19. Cytokines promoting B cell activation, proliferation and differentiation
B cells are activated by antigen on antigen presenting cells such as macrophages in the presence of IL-4 and IL-1. This cause expression of receptors for IL-2 and other cytokines. IL-2, IL-4 and IL-5 drive cell division. Differentiation into antibody-forming cells is effected by IL-4,5,6,10 and IFN-gamma.

20. B cells proliferation and differentiation
Active B cell express many CKR
 receive stimuli of CK from Th
 IL-2,IL-4,IL-5 promote B cell proliferation，
IL-4,IL-6,IFN-g promote B cell differentiation.

21. B cell mature in germial center
* Somatic hyper-mutation and Ig affinity maturation
*Antigenic receptor editing： Ig gene rearrangement occur in auto-reactive B cell, edited BCR point at none-self Ag.
*Ab class switch：V region does not change，only C region of H chain change.。

22. B cells enter into primary follicle
1. Antigen loaded dendritic cells migrate from subcapsular sinus to paracortical area of the lymph node DC
B cells (90%) and T cells (10%) migrate to a primary follicle B T
B cells enter into primary follicle T
3. T cells proliferate T
2. T cells migrate through HEV and are trapped by antigen on DC B B
4. B cells migrate through HEV - most pass through the paracortex and primary follicle.
HEV
Some interact with T cells and proliferate to form a primary focus

23. Cytokines and antibody isotype switch
The antibody isotype switch is affected by cytokines.
- IFN-gamma promote the switch of the antibody from IgM to IgG2a or IgG3.
- IL-4 induces the switch of antibody to IgE or IgG1
-Il-2,4,5 promote IgM production.
Flash

24. B cell mature in germial center
* Somatic hypermutation and Ig affinity maturation
*Antigenic receptor editing： Ig gene rearrangement occur in autoreactive B cell, edited BCR point at none-self Ag.
*Ab class switch：V region does not change，only C region of H chain change.。

25. B cell primary response toTD-Ag
APC take in,process and present Ag
B7-CD28
IL-1
TCR recognize peptide/MHCII
B/Th interaction
CD40/CD40L binding
BCR recognize B cell epitope
Th develop
Signal 2
Signal1
secretIL-2、IL-4、IL-5、IL-6
B cell develop
Mature in germinal center PC
（early）IgM
（die after 2 Wk）
Memory B PC
（late）IgG
（enter lymphocyte re-cycle）
（in bone marorw）

26. Primary and secondary response

27. （Primary immune response）
初次免疫应答
（Primary immune response）
Ir induced by pathogen first invaded human body.
Properties：
- longer lag phase；
- Most class of Ab is IgM ；
- Level of Ab is low；
- Affinity of Ab is low.

28. Four phases
潜伏期
对数生长期
平台期
下降期

29. （secondary immune response）
再次免疫应答
（secondary immune response）
The same Ag reenter body, stimulate memory cells to elicit prompt, efficacy and specific response.
Properties：
- APC (memory B) interact with memory T；
- Low amount of Ag for simulation；
- Lag phase shorter；
- Ab Level higher, Ab duration longer；
- Most class of Ab is IgG ，affinity higher。

30. Primary and secondary humoral immune responses

31. Memory B cells present antigen to T cell

32. Raising Ab production and affinity after repetitive immunization

33. Primary and Secondary Immune Response
Ab concentration
Total amount of Ab
IgG
Lag phase
Lag phase
IgM 10 3
First stimuli of Ag
Repetitive stimuli of the same Ag
Days

34. Difference of primary and secondary response
Features
secondary
Ag stimulation
Lag phase
Ab peak
duration
Ig Class
affinity
first
second
5-10 days
lower
shorter
IgM
low
2-5 days
higher
longer
IgG、IgA
high

35. Effect of B cell response

36. Neutralization By Antiviral Antibodies

37. Effector mechanisms against extracellular pathogens
(2) OPSONISATION
Bacteria in extracellular space Ab +
Fc receptor
binding
Phagocytosis
Antibodies can bind the epitopes on pathogen. The Fc regions of antibodies can bind to Fc receptors expressed on phagocytes, then promote the phagocytosis.
OPSONISATION

38. Action of phygosytosis

39. Complement activation
(3)
Complement activation

40. Phagocytosis binding Complement & Fc receptor Opsonisation
Effector mechanisms against extracellular pathogens
COMPLEMENT Activation
Bacteria in plasma
Lysis
Ab &
COMPLEMENT +
Phagocytosis
binding
Complement &
Fc receptor
Opsonisation
Bacteria in plasma bind antibodies to form antigen-antibody complex which can activate complement by classical pathway of complement activation. The activation of complement can leads to the lysis of bacteria by membrane attack complex. The antibodies can use their Fc regions to bind Fc receptors on phagocytes and complement fragments such as C3b can bind to C3bR on phagocytes which promote phagocytosis.

41. FcgR and Complement Receptors Cooperate To Induce Greater Phagocytosis

42. (4) .Effector cells of ADCC
ADCC can be mediated by NK cells, macrophages, neutrophils and eosinophils.

43. (4)

44. (5) IgA against adhesins

45. (6) Immune damage IgE Antibody Binds To Mast Cells & Basophils To Arm Them For Mediator Release

46. B cell response to TI Ag

47. Do not require Th，without immune memory，occur earlier.
TI-1Ag activate B cell
- At high concentration,TI-1Ag induce activation of many B cells (polyclonal activation)
- At low concentration, TI-1Ag induce activation of specific B cell.
* TI-2 Ag direct activate mature B1 cell
- Repetitive epitopes bind BCR→BCR cross-linkage→produce IgM

49. Mechanism for TI-Ag activate B cell
（A）： TI-1 Ag
（B）： TI-2Ag

50. High Repeatitive epitopes
mitogen
LPS
TI-1
TI-2
SmIg
epitope
capsule of pneumococcus
SmIg
High Repeatitive epitopes
mitogen R B B2 ① ②
Signal
Signal
Activate
Activate
B cell activation induced by TI antigen

51. Thymus dependent Ag(TD—Ag) Thymus independent Ag(TI—Ag)
Comparison items
Thymus dependent Ag(TD—Ag)
Thymus independent Ag(TI—Ag) Th
require
No require
Class of Ir
Humoral and cellular
Only humoral
Class of Ab
most are IgG
Only IgM
Memory reaction
Yes
Not

52. Effect of B cell mediated Ir
* Neutralization：Neutralize toxin 、virus
* Opsonization ：Ag coated with IgG and IgA，promote phygocytosis
* Activation of complement：（IgG/IgM）IC，activate classical pathway
- CDC
- Opsonization
* ADCC：NK、M、NC、EC
* Mucous defense of secretary IgA
* Immune damage:
- hypersensitivity and AID
- Graft rejection reaction：preformed Ab cause hyper acut reaction
- promote tumor growth ：blocking factor，interrupt CTL reorganization to tumor Ag

54. Review Question
Describe the process of B cell response to TD Ag in primary immune response简述B细胞对TD-Ag的初次免疫应答过程。
Compare primary and secondary immune response , describe their significance in application 简述体液免疫应答的一般规律和了 解此规律的意义。
Describe the admission molecules and their functions involved in T-B interaction简述参与T-B细胞相互作用的黏附分子及 其功能。