2. Chapter 11. Immune response (1) I. Introduction II. Antibody-mediated Humoral Immunity

3. I. Introduction 1. Concept of Immune Response 2. Types of Immune Response 3. Process of Immune Response

4. 1. Immune response The immune system of body is able to recognize subtle chemical differences that distinguish one foreign pathogen from another. At the same time, the system is able to discriminate between foreign molecules and the body’s own cells and proteins. Once a foreign organism is recognized, the immune system eliminate or neutralize the organism, finally. The immune system of body is able to recognize subtle chemical differences that distinguish one foreign pathogen from another. At the same time, the system is able to discriminate between foreign molecules and the body’s own cells and proteins. Once a foreign organism is recognized, the immune system eliminate or neutralize the organism, finally.

5. 2. Types of Immune Response Autoimmunity selection Immune “Self”Ag Autoimmune Tolerance Ag system: activation “non-self”Ag HI / CMI Immune Tolerance Hypersensitivity Reaction

6. II. Antibody-mediated Humoral Immunity concept of HI ， simple process of HI 1. Common rule of Ab production 2. Interaction between immune cells in process of producing Ab process of producing Ab 3. Immune Memory 4. Effect of Humoral Immunity

7. Humoral Immunity ， HI Humoral Immunity ， HI Humoral immunity is mediated by antibodies of various different classes; which Ab are produced by cells of the B cell lineage in response to stimulation by Ag. Humoral immunity is mediated by antibodies of various different classes; which Ab are produced by cells of the B cell lineage in response to stimulation by Ag.

8. Simple process of HI: 1 、 TD—Ag APC TH BL2 THm BLm THm BLm 2 、 TI—Ag BL1 Mature B cell Plasma cells Plasma cells Ab HI Ab HI

9. 1.Common rule of Ab production a. The regularity of Ig production in phylogenic evolution and development,and ontogenesis. b. The regularity of Ab production in the primary and secondary response 。

10. Secondary Immune Response When the immunized individual after a primary contact with antigen is injected by a second injection of the same antigen, production of antibody becomes apparent, this response is called the secondary response.

11. Primary IR Secondary IR Antigen The first contact of an A second injection of the individual with an Ag same Ag latent period long (1W ， 2-3W) short (1-3day) slow of Ab production Ab Conc. low in serum high in serum Maintain Time short,decrease quickly longer type of Ig IgM IgG Affinity lower higher present of Ag M , DC B cell

12. Concentration of Ig Ig IgM IgG 10day3day Latent period Primary stimulation of Ag Secondary stimulation of Ag

13. 2. Interaction between immune cells in the process of producing Ab TD—Ag response a. Interaction between M  and Th cells * M  presented Ag *Interaction between cells * M  presented Ag *Interaction between cells b. Interaction between Th cell and B cells * B cell presented Ag * Interaction between cells * B cell presented Ag * Interaction between cells c. Interaction between M  and B cells TI—Ag response B cell : response of TI—Ag B cell : response of TI—Ag

14. Ags are ingested, processed, presented by M  (primary response) Ags are ingested, processed, presented by M  (primary response) n Ingestion ： endocytosis, passive adhesion 。 Processing ： lysosomal enzymes condense and degrade Ag, and combine to self-MHCII molecules. Processing ： lysosomal enzymes condense and degrade Ag, and combine to self-MHCII molecules. n Presentation ： These complexes of peptide and MHC molecules are transported to the surface of the cell where they are recognized by the T-cell receptor.

15. Exogenous Ag endosome Transportation combination degradation expression endocytosis APC CD4 TCR MHCII

16. transcription DNA mRNA Virus （ endogenous Ag ） translation Pr degradation CD8 CTL MHCI Target cell TCR

17. Interaction between M  and Th cells （ primary response ） Interaction between M  and Th cells （ primary response ） Double signal hypothesis of Th cell activation ： The first signal ： Th: TCR/CD3——APC: Ag-MHCII complexes Th: TCR/CD3——APC: Ag-MHCII complexes at the same time, TH: CD4——APC: The  2,  2 domain of MHCII at the same time, TH: CD4——APC: The  2,  2 domain of MHCII The second signal ： APC: B7/BB1 （ CM ） ——TH: CD28 （ CMR ） APC: B7/BB1 （ CM ） ——TH: CD28 （ CMR ） TH secreted IL-2 and expressed IL-2R TH secreted IL-2 and expressed IL-2R Finally cells divide, clones proliferation, and produce a kind of CK. Finally cells divide, clones proliferation, and produce a kind of CK.

18. ICAM-1LFA-1 APC (CMs) MHC-II Ag B7/BB1 VLA-4 VCAM-1 CD2 CD58 Cell activation, （ CK ） cell differentiation and clone proliferation TH (CMRs) TCR CD3 CD4 CD28 CTLA4 Signal 1 Signal 2 IL-2 IL-2R Interaction between APC and Th cell

19. MHC-Ag APC TCR/CD3 B7/BB1 CD28 TH Signal 1 Signal 2 IL-2 production clone proliferation APC TH Signal 1 Signal 2 not IL-2 production clone anergy

20. inactivation Suppressive immune response ： Hypersensitivity Disease Hypersensitivity Disease Autoimmunity Disease Autoimmunity Disease Graft rejection responses Graft rejection responses Anti-B7Ab CTLA4 Ig Anti-CD28 Interdiction of co-stimulatory signals TH APC MHC TCR Ag CD28 B7

21. Enhancing immune response ： Tumor immunity treatment Tumor immunity treatment B7 Transfection B7gene CTL MHCTCR Ag CD28 Tumor cell signal1 signal2 CTL MHC TCR Ag CD28 Tumor cell signal1 signal2 CTL activated Killer tumor cell CTL activated Killer tumor cell

22. Interaction between Th and B cells （ secondary response ） Interaction between Th and B cells （ secondary response ） Th cell activation ： Double signal hypothesis Signal 1 ： Th: TCR/CD3——B cell: Ag-MHCII complexes Th: CD4——B cell: The  2,  2 domain of MHCII Th: CD4——B cell: The  2,  2 domain of MHCII Signal 2 ： Th: CD28 molecule ——B cell: B7 molecule. B cell activation ： Double signal hypothesis Signal 1 ： B cell: BCR--Ag ， Ig ,Ig  transfer activation signal 1 B cell: CD40——Th: CD40L Signal 2 ： B cell: CD40——Th: CD40L Th and B cell inducing signal of activation each other ， Th produced IL-4,5,6. B cell is helped at Th cell, finally B cell proliferated and differentiated turn into the plasma cells of producing a kink of Igs.

23. CD3 singal B cell activation B cell Ag SIg 1 2 Signal 1 T cell B7 CD28 ICAM-1 LFA-1 CD3 TCR CD4 MHC-II CD40L CD40 LFA-1ICAM-1 Signal 2 Th activation CK Ag process present Interaction between B cell and T cell CKR

24. Ag Bm BB BB PC IgMIgG IgAIgE Bm Activate Th Activate B IL-2 ， 4 ， 5 ， 6 IL-1 process present process present proliferation ingestion MHC-II TCR MM MM differentiation c. Interaction between M  and B cells

25. signal B cell I type: TI—Ag is polyclonal stimulator II type: multiple repeat-lined antigenic determinant makes receptor linkage TI-Ag response

26. 3. Immune Memory - Secondary response Characteristic : a. Immune memory cells b. Class switching of Ig c. Affinity Maturation of Ab

27. Characteristic ： * Immune memory cells: THm Bm * Involved in Humoral immunity and cell-mediated immunty. * Ab conc. increases ， class switching of Ab ， and affinity maturation of Ab

28. 4. Effect of Humoral Immunity n Neutralization of Ab n Opsonization of Ab n Complement dependent cell-mediated cytotoxicity,CDC n Antibody dependent cell-mediated cytotoxicity,ADCC n Immune regulation of Ab

29. Opsonization of Ab Bacteria Anti-bacteria Ab MM FcrR Boost up lick up action

30. Target cell M , NK Dissolution of target cell IgG Surface Ag FcrR Antibody-dependent cell-mediated cytotoxicity, ADCC

31. Chapter12. Immune response (2) I. Introduction II. CD4 T-mediated immunity III.CD8 T-mediated immunity

32. I. Introduction 1. Concept, Simple process 1. Concept, Simple process 2. Major functions of CMI 2. Major functions of CMI

33. Simple process: TD-Ag Immune system secondary T DTH Tc CK Cytotocixity

34. 2. Major Functions of CMI n Delayed Type Hypersensitivity, DTH n Intracellular Anti-infection n Anti-tumor n Transplantation rejection reaction Graft Versus Host Reaction, GVHR Graft Versus Host Reaction, GVHR n Autoimmunity diseases

35. II. CD4 T-mediated immunity 1. Activation of CD4 T cells 1. Activation of CD4 T cells 2. Formation of DTH inflammation 2. Formation of DTH inflammation * CK production * Function of M  * CK production * Function of M 

36. Activation of CD4 T cells Double signal hypothesis of CD4 T cell activation ： The first signal ： Th: TCR/CD3——APC: Ag-MHCII complexes Th: TCR/CD3——APC: Ag-MHCII complexes at the same time, TH: CD4——APC: The  2,  2 domain of MHCII at the same time, TH: CD4——APC: The  2,  2 domain of MHCII The second signal ： APC: B7/BB1 （ CM ） ——TH: CD28 （ CMR ） APC: B7/BB1 （ CM ） ——TH: CD28 （ CMR ） TH secreted IL-2 and expressed IL-2R TH secreted IL-2 and expressed IL-2R Finally cells divide, clones proliferation, and produce a kind of CK. Finally cells divide, clones proliferation, and produce a kind of CK.

37. IL-2R APC (CMs) TH (CMRs) CD28 CTLA4 CD3 TCR CD4 ICAM-1LFA-1 MHC-IIAg B7/BB1 VLA-4 VCAM-1 CD2 CD58 Signal1 Signal 2 IL-2 IL-2R Cell activation, （ CK ） cell differentiation and clone proliferation

38. APC T T T T T T T IL-2 IFNr TNF T M rest M activation CK of DTH reaction

39. III.CD8 T-mediated immunity 1. Activation ofCD8 T cells 2. Mechanisms of Tc killing target cells a. Perforin a. Perforin b. Granzymes b. Granzymes c. TNF associated proteins c. TNF associated proteins

40. Activation of CD8 T cells Double signal hypothesis of CD8 T cell activation ： The first signal ： Tc: TCR/CD3——Target cell: Ag-MHC-I complexes Tc: TCR/CD3——Target cell: Ag-MHC-I complexes at the same time, Tc: CD4——Target cell: The  3 domain of MHC-I at the same time, Tc: CD4——Target cell: The  3 domain of MHC-I The second signal ： Target cell: B7/BB1 （ CM ） ——Tc: CD28 （ CMR ） Target cell: B7/BB1 （ CM ） ——Tc: CD28 （ CMR ） Tc secreted IL-2 and expressed IL-2R Tc secreted IL-2 and expressed IL-2R Finally cells divide, clones proliferation, and secrete effect molecules. Finally cells divide, clones proliferation, and secrete effect molecules.

41. Interaction between target cell and Tc ICAM-1LFA-1 Target cell (CMs) MHC-I Ag CD2 CD58 Tc (CMRs) TCR CD3 B7/BB1 CTLA4 Signal 1 Signal 2 IL-2R CD8 Cell activation, differentiation, clone proliferation and secreted effect molecules. IL-2

42. Ag recognition Tc activation Tc killed target cell Tc unbind Target cell died

43. TH1 Effector Tc Rest Tc Target cell APC MHCI MHCII IL-2 ， IL-6 ， IFN TCR death Target cell