Characteristic and mechanism of specific immune response

1. Chapter 13 Characteristic and mechanism of specific immune response

2. 教学大纲 • 掌握免疫耐受的概念、特性 • 熟悉免疫应答的特异性、记忆性的特点 • 熟悉免疫耐受形成的机制 • 了解BCR、TCR多样性及其分子基础、基因重排和多样性的机制 • 了解免疫耐受的形成、维持和终止的生物学意义。

3. Characteristics of specific immune response specificity memory tolerance acquired、reject diversity、transferable

4. Major contents * Specificity of Ir * Memory of Ir * Tolerance of Ir

5. Specificity of immune response Have antigen specificity Certain antigenspecific antibody sensitive lymphocyte Specific binding

6. Molecule basis of specificity • Diversity of TCR/BCR

7. Memory of immuneresponse concept：when antigen first enter the body ,the activated signals and effect signals can keep in immune system. Therefore ,when the same antigen reenter the body , the immune response against the antigen will be prompt , stronger and efficacy。

8. Physical basement： Tm，Bm , high affinity of specific TCR and BCR, stronger antigen presenting ability, etc. Secondary immune response only mediated by memory lymphocyte.

9. T cell mediated immune memory • Tm is easier to be activated than naive T cell ;require lower level antigen • Weak dependence on co-stimulator for activation(CD28/B7) • Tm secrete more CKs than naive T cell , higher sensitivity to CKs

10. B cell mediated immune memory • Bm Produce higher affinity antibodies; • Can develop Ab class switch; • Express more mIgG , higher level IgA、IgE and MHC-II molecule， facilitate to taking in and presenting of antigen, low concentration of Ag can activate Th and B cell

11. Biological significance of Tm and Bm： has important significance for host against reintroduce of pathogen provide the theoretical basis for vaccination

12. Tolerance of immune response * Concept and characteristic of immune tolerance * Induce of immune tolerance * Forming mechanism of immune tolerance * Significance of studying immune tolerance

13. Tolerance of immune response An unique form for specific immune response *innate tolerance *acquired tolerance

14. Owen于1945年发现异卵双胎小牛胎盘血管互相融合，出生后体内均存在两种不同血型的红细胞，即形成红细胞嵌合体（chimeras），并互不排斥。Owen于1945年发现异卵双胎小牛胎盘血管互相融合，出生后体内均存在两种不同血型的红细胞，即形成红细胞嵌合体（chimeras），并互不排斥。

15. Non-identical twins

16. Medawar胚胎诱导耐受实验(1953年)

18. Dresser demonstrate :Adult mice may be induced immune response (1962年) 天然BSA tolerance Embryo mice soluble BSA tolerance Adult mice

19. 免 疫 耐 受 (Immune tolerance) immune tolerance is a state of unresponsiveness or low responsiveness that is specific for a particular antigenafter host contacted the antigen.

20. Forming of immune tolerance Self or foreign antigen stimulate embryo Immature T cells and B cells form immune tolerance after birth Not produce immune response for the same antigen

21. tolerogen：a class of antigen that induce immune tolerance • can be innate tolerance，also can be acquired tolerance • antigenic specificity

22. ◆ similar with immune response： Require antigen stimulation，have lag period、antigenic specificity、memory. ◆ Immunosuppression ： no antigenic specificity ， unresponsiveness or low responsiveness for all kinds of antigen

24. 免疫反应 免疫原 免疫原 免疫正应答 +++ 7-14天 4-6周 耐受原 免疫原 免疫负应答 4-6周 7-14天  Have lag period

25. Similarities and differences between immune positive response and immune tolerance Irtolerance Antigenstimulation need need lag period have have specificity + + memory + + intensity strong no or weak effect reject foreignprotect self

26. common characteristics of immune tolerance • is antigenic specificity • is induced easily by immature lymphocytes • maintenance of immune tolerance requires persistent existing of tolerogen • in some cases ,can be induced by mature lymphocytes

27. Tolerance of immune response * Concept and characteristic of immune tolerance * Induction of tolerance * Mechanisms of immune tolerance * Significance of studying immune tolerance

28. Induction of tolerance • antigen factors • host

29. antigen factors 1. Properties of antigen • Type of antigen：monomer • Has similar background of heredity for host • Small molecule • Soluble antigen

30. 2. antigen dosage T I -Ag：high doses B cell tolerance TD-Ag：high doses T、B cell tolerance low doses T cell tolerance (high- zone tolerance) （low-zone tolerance）

32. Major features of low zone tolerance and high zone tolerance low zone tolerancehigh zone tolerance Involved cell T T、B Speed for inducing rapidly slowly Duration long short Types of antigen TD-Ag TD、TI-Ag

33. major differences between T cell tolerance and B cell tolerance T cell B cell tolerogen TD-Ag TD、TI-Ag Doses of antigen high or low high Lag period short (24h) long (70 days ) Duration long (months) short (weeks) Forming of tolerance easier difficult mechanism central clone deletion clone abortion peripheral lack of B7 suppress SIgM anergyexpression

34. （一）antigen factors 3. The routes of administration mainline / oral administration >subcutaneous / muscle injection 4. others adjuvant

35. （二）host factors * Maturation of immune system（ages） embryo＞ neonatal＞ adult * State of host use immunosuppressant to damage mature lymphocytes (intrauterine)

36. Tolerance of immune response * Concept and characteristic of immune tolerance * Induction of tolerance * Mechanisms of immune tolerance * Significance of studying immune tolerance

37. Mechanisms of immune tolerance * Central tolerance is induced by immature T、 B lymphocytes of embryo immune system contact antigen in generative lymphoid organs. * Peripheral tolerance is induced when mature T 、B lymphocytes contact antigens in peripheral lymphoid organs.

38. Central tolerance T cell and B cell develop in thymus and bone marrow，in which perform negative selection Initiate cell apoptosis ,cause clonal deletion Reduce development of AID

39. Central tolerance Mechanism of clonal deleted（negative selection) in thymus or bone marrow ,TCR or BCR of self reactive T B cells bind to self peptide-MHC molecule expressed on the surface of microenvironment stroma cell with high affinity ，initiate cells apoptosis，elicit clonal deletion。 Flash

40. Central tolerance: （clonal deletion theory） 胚胎期免疫系统接触特定抗原后，针对该抗原的特异性细胞克隆即被清除或被“禁闭”，机体将该抗原视为自身成份，出生后将不对此抗原产生应答。

41. 动 画 演 示 T 细胞的选择过程 • Positive selection • Negative selection

44. Functions of negative selection • Negative selection of T、B cells make human establish central tolerance against self antigen. • Failure of negative selection ,may be cause autoimmune disease.

45. Peripheral tolerance Reasons of self reactive T、 B cells escaping central tolerance • Thymus or bone marrow stroma cell not express tissue specific antigen resourced from some peripheral organs or antigen expressed after maturation. • Low expression of self antigen or affinity of BCR or TCR is too low.

46. Peripheral tolerance Clonal anergy and immune ignorance Low levels of most tissue specific antigen，can not activate T B cells. If concentration of antigen is moderate, self reactive T cell bind with self peptide MHC-I complex of tissue cell (signal 1)，but tissue cell not express co-stimulatory molecule (no signal 2) →apoptosis → clonal anergy Flash

47. Mechanism of peripheral tolerance • Clonal anergy and immune ignorance Lack of activated signal * lack active signal 1： * lack co-stimulating signal：（clonal anergy）

49. 2）clonal apoptosis *mature T cells contact self antigen---produce apoptosis signal ---T cell apoptosis • 3） activation of Ts cells * release inhibitory cytokines----close signal transduction pathway of associated T cells. (IL-10,TGF-β）