1. Medical Immunology 吉林大学基础医学 院免疫学教研室 1 Overview of Immunology Organs and tissues Cells Molecules － Antibodies － Complement － Cytokines － MHC Components of IS Functions of IS Pathology of IR * IS: Immune system IR: Immune response Applications Prevention Diagnosis Therapy Antigen (Ag) Immune Responses Control mechanisms Hypersensitivity Autoimmune disease Immunodeficiency Tumor Transplantation rejection

2. 2 Ag APCs Th1 Tc B Ab PMN NK Th2 Complement Immune Response (IR) Targetcells MHCCKs MHCCKs CKs CKs CKs

3.  What are cytokines(CK)?  Classification of CKs.  General characteristics of CKs.  Biological Activities of CKs.  Clinical Application of CKs.

4. What are cytokines? Cytokines are low-molecular weight regulatory proteins or glycoproteins secreted by the immune cells and related cells in the body in response to a number of stimuli.

5. Inducing stimulus Cytokine genes Cytokine- producing cells Cytokine Gene activation Receptor signal Biological effects High affinity-high performance Self restriction Short half-life Antigen-nonspecific manner

6. What are cytokines? Cytokines are low-molecular weight regulatory proteins or glycoproteins secreted by the immune cells and related cells in the body in response to a number of stimuli. Cytokines(CKs) regulate the intensity and duration of the immune response by: stimulating or inhibiting the activation, proliferation, and/or differentiation of various cells, regulating the secretion of antibodies or other cytokines or mediators. 6

7.  What are cytokines?  Classification of CKs.  General characteristics of CKs.  Biological Activities of CKs  Clinical Application of CKs

8. Categories of CKs Interferons(IFNs): IFNα/ IFNβ/ IFNγ Tumor necrosis factors(TNFs): TNFα/ TNFβ Interleukin(ILs):IL-1~IL-37 Chemokines: Colony stimulating factors(CSFs): GM-CSF/M-CSF/G-CSF/EPO Transforming growth factors (TGFβs): TGFβ-1/ TGFβ-2/ TGFβ-3

9.  What are cytokines?  Classification of CKs.  General characteristics of CKs.  Biological Activities of CKs  Clinical Application of CKs

10. 10 General characteristics of CKs  Small molecules  Secreted by ： ⑴ Immune Cells; ⑵ Related cells - Autocrine - Paracrine - Endocrine

12. 12 General characteristics of CKs  Small molecules  Secreted by ： ⑴ Immune Cells; ⑵ Related cells - Autocrine - Paracrine - Endocrine  Bind with specific receptor

14. 14 General characteristics of CKs  Small molecules  Secreted by ： ⑴ Immune Cells; ⑵ Related cells - Autocrine - Paracrine - Endocrine  Bind with specific receptor  Effector : - Pleiotropy

16. 16 General characteristics of CKs  Small molecules  Secreted by ： ⑴ Immune Cells; ⑵ Related cells - Autocrine - Paracrine - Endocrine  Bind with specific receptor  Effector : - Pleiotropy - Redundancy

17. 17

18. 18 General characteristics of CKs  Small molecules  Secreted by ： ⑴ Immune Cells; ⑵ Related cells - Autocrine - Paracrine - Endocrine  Bind with specific receptor  Effector : - Pleiotropy - Redundancy - Synergy

19. 19

20. 20 General characteristics of CKs  Small molecules  Secreted by ： ⑴ Immune Cells; ⑵ Related cells - Autocrine - Paracrine - Endocrine  Bind with specific receptor  Effector : - Pleiotropy - Redundancy - Synergy - Antagonism

21. 21

22. 22 General characteristics of CKs  Small molecules  Secreted by ： ⑴ Immune Cells; ⑵ Related cells - Autocrine - Paracrine - Endocrine  Bind with specific receptor  Effector : - Pleiotropy - Redundancy - Synergy - Antagonism - Cascade induction

23. 23

24. 24

25. 25 General characteristics of CKs  Small molecules  Secreted by ： ⑴ Immune Cells; ⑵ Related cells - Autocrine - Paracrine - Endocrine  Bind with specific receptor  Effector : - Pleiotropy - Redundancy - Synergy - Antagonism - Cascade induction

26.  What are cytokines?  Classification of CKs.  General characteristics of CKs.  Biological Activities of CKs  Clinical Application of CKs

28. 28 Cells of IS are produced from haemopoietic stem cells (HSC) in BM. Stromal cells (epithelial cells, fibroblast, macrophage) is required for the differentiation of a particular lineage. Cytokines( CSF) produced from stromal cells provide the local environment for the hematopoiesis. Function of CKs --in the Bone Marrow

29. CKs CKs CKs CKs CKs CKs CKsCKs CKs CKs CKs CKs CKs CKs

31. 31 Ag APCs Th1 Tc B Ab PMN NK Th2 Complement Immune Response (IR) Targetcells

32. 32 Ag APCs Th1 Tc B Ab PMN NK Th2 Complement Immune Response (IR) Targetcells MHCCKs MHCCKs CKs CKs CKs

33. 33 Ag M Th1 Tc B Ab PMN NK Th2 Complement Immune Response (IR) Targetcells IL-12 IFN- γ IL-4IL-10 IL-2 IL-4IL-5IL-6IL-10 IL-1IL-2IL-6

35. Counter regulation of Th cell subsets - Th1 - IL-12, IFN- γ IL-4, IL-10 - Th2 Balanced response Th1 Th2 IL-4, IL-10 Th2 dominant Th1 IL-12, IFN- γ Th2 - Th1 dominant

36. Activation Clonal proliferation Maturation CKs G1G1 S S G0G0 THTH CKs CKs IgE/IgDIgA IgMIgG CKs B cell activation and Ab production Ag

37. Activation Clonal proliferation Maturation IL-4,13(2) G1G1 IL-4 TGFβ IL - 5 S S G0G0 THTH IL-4,5 IL-4,5,6 IFNγ IgE/IgDIgA IgMIgG IL-2,4,5,6,13,IFNγ B cell activation and Ab production Ag

38.  What are cytokines?  Classification of CKs.  General characteristics of CKs.  Biological Activities of CKs  Clinical Application of CKs

39. Clinical Application of CKs Supplement Suppression 39

40. Clinical Application of Cytokines - Supplement 1) Interferon in treatment of viral diseases. 2) IL-2 and IFN-  are used to enhance T-cell activation in immunofideficincy diseases. 3) IL-2 and lymphokine activating killer cells (LAK) in treatment of cancer. 4) GM-CSF induces increase in white cell count, it is used: a- To restore leukocytic count after cytotoxic chemotherapy induced neutropenia. b- After bone marrow transplantation. C- To correct AIDS-associated leukopenia.

41. Clinical Application of Cytokines - Suppression How?

42. Clinical Application of Cytokines - Suppression 1) Anti-IL-2R to reduce graft rejection. 2) Anti-TNFR in treating rheumatoid arthritis. 3) Anti-IL-2R  in treating adult T-cell leukemia. 4) Anti-IL-4 is under trial for treatment of allergies.

43.  What are cytokines?  Classification of CKs.  General characteristics of CKs.  Biological Activities of CKs  Clinical Application of CKs