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Chapter 7 Cytokines (CKs)

Chapter 7 Cytokines (CKs). Contents. PartⅠ Definition and general properties of cytokines PartⅡ Classification of cytokines PartⅢ Cytokine receptor PartⅣ Biological functions of cytokines PartⅤ Cytokine and disease. Part Ⅰ Definition and general properties of cytokines.

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Chapter 7 Cytokines (CKs)

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  1. Chapter 7Cytokines (CKs)

  2. Contents • PartⅠ Definition and general properties of cytokines • PartⅡ Classification of cytokines • PartⅢ Cytokine receptor • PartⅣ Biological functions of cytokines • PartⅤ Cytokine and disease

  3. PartⅠ Definition and general properties of cytokines Ⅰ. Definition • A group of low molecular weight polypeptides or proteins which are secreted by activated immunocytes or some matrix cells and possess high activity and various functions. • Their major functions are to mediate and regulate immune response and inflammatory reactions.

  4. Ⅱ. General properties of cytokines 1.Most cytokines are low molecular weight polypeptides or glycoprotein(8~80 KD), and most of them are monomer. • Monomer, dimer, trimer • Soluble, membrane-bounded

  5. 2. Natural cytokines are secreted by activated cells • Such asactivated immune cells,matrix cells and some tumor cells. • Ag, SAg, mitogen

  6. 3.One kind of cytokines can be produced by different cells. One kind of cells can secrete different cytokines. IL-3,GM-CSF,TNF- IL-2 IL-4, 6 Th1 Th2 IFN-γ, TNF-β IL-5

  7. 4. Cytokines act on target cells by the way of paracrine, autocrine or endocrine. • Cytokines can act on the cells that produce them (autocrine), on other cells in the immediate vicinity (paracrine), or on cells at a distance (endocrine) after being carried in blood or tissue fluids.

  8. 5.Cytokines initiate their actions by binding to specific membrane receptors on target cells. • Receptors for cytokines often bind their ligands with high affinities. • Kd 10-10-10-12 Antibody and antigen: Kd 10-7-10-11 MHC-peptide and TCR: Kd 10-5-10-7

  9. Low concentration (pmol/L) • Most cells express low levels of cytokine receptors, and this is adequate for inducing response. • So only small quantities of cytokines are needed to occupy receptors and elicit biologic effects.

  10. 6. The effects of cytokines are often pleiotropism, redundant, synergy, antagonism, and form a cytokine network. • Pleiotropism refers to the ability of one cytokine having multiple effects on diverse cell types.

  11. Redundancy refers to the property of multiple cytokines having the same or overlapping functional effects.

  12. Synergy refers to the property of two or more cytokines having greater than additive effects.

  13. Antagonism refers to the ability of one cytokine inhibiting the action of another.

  14. 骨髓基质细胞 下 丘 脑 造血干细胞 IL-1 IL-6 TNF-a IL-1 IL-6 IL-7 SCF IL-1 IL-6 IL-11 TNF-a GM-CSF G-CMF M-CSF 内皮细胞 IL- 4 M-CSF GM-CSF IL-1 TNF-a 单核细胞 IL- 4 M-CSF GM-CSF Mj IL-1 TNF-a 纤维母细胞 IL-1 TNF-a TGF-b PDGF FGF 中性粒细胞 IL-1 IL-8 TNF-a IL-12 IL-10 IL- 4 G-CMF IFN-g GM-CSF IL-10 IL-13 IL-4 TGF-b IL-2 IFN-g IL-2 NK 细胞 IL-2 IL-12 IL- 4 IL-6 TH1 TH2 Tc B IFN-g 嗜酸性粒细胞 IL-10 IL-13 IL-4 IL-4 IL-2 IL- 4 IL-4 IL-5 IL-6 IL-13 IL-10 TGF-b IL-2 IFN-g IL-4 IL-4 IL-4 IL- 6 内皮细胞 NK1+T

  15. PartⅡ Classification of cytokines • Interleukin, IL • Interferon , IFN • Tumor necrosis factor, TNF • Colony stimulating factor, CSF • Chemokine  • Transforming growth factor

  16. Ⅰ. Interleukin (IL) • Cytokines secreted by leukocytes that have the ability to act as signal molecules between different population of leukocytes • IL-1~IL-38

  17. Ⅱ. Interferon (IFN) A group of glycoproteins that produced by human or animal cells following the infection of virus and exposure to various inducing agents

  18. Comparison of IFN-, IFN-, IFN- _____________________________________ Types Produced cells Main functions ____________________________________ IFN- leukocyte anti-virus,immune regulation IFN- fibroblast anti-tumor IFN---Type II Th1,NK ------- weaker anti-virus effect stronger immune regulation effect anti-tumor _____________________________________ Type I

  19. Ⅲ.Tumor necrosis factor (TNF) TNFs were originally thought of as selective antitumour agents, but are now known to have a multiplicity of actions. • TNF- is produced mainly by LPS activated monocytes and macrophages. • TNF-(lymphotoxin, LT) is produced mainly by activated Th0 and Th1.

  20. Ⅳ. Colony-stimulating factors (CSF) Cytokines that stimulate proliferation or differentiation of pluripotent hematopoietic stem cell and different progenitors. • Multi-CSF (IL-3) • Granulocyte macrophage-CSF(GM-CSF) • Monocyte-CSF(M-CSF) • Granulocyte-CSF(G-CSF) • Stem cell factor(SCF) • Erythropoietin(EPO)

  21. Ⅴ. Chemokine Chemokines are cytokines which recruiting monocytes,granulocytes and lymphocytes in blood to the sites of inflammation. • CXC chemokines(α subgroup):IL-8 • CC chemokines(β subgroup):MCP-1 • C chemokines(γ subgroup) • CX3C chemokines(δ subgroup) *C: cysteine; X: any amino acid

  22. Ⅵ. Transforming growth factor Growth-factor are cytokines which stimulate the growth and differentiation of their target cells. • Transforming growth factor-(TGF- ) • Epithelia growth factor(EGF) • Vascular endothelia cell growth factor(VEGF) • Fibroblastic growth factor(FGF)

  23. PartⅢ CK receptor 1. Membrane-binding cytokine receptors: The receptor consists of extra-cellular region, trans-membrane region and cytoplastic region.

  24. CK receptors can be grouped into five families according to structure and function: (1) Ig receptor superfamily:IL-1R,PDGFR,FGFR (2) Type Ⅰ CK receptor superfamily: CSFR (3) Type Ⅱ CK receptor superfamily: IFNR (4) Type Ⅲ CK receptor superfamily: TNFR (5) G-protein linked receptor superfamily: CCR5

  25. Low affinity IL-2R Moderate affinity IL-2R High affinity IL-2R IL-2 g g a a b b IL-2 receptor

  26. Three forms of the IL-2 Receptor (CD25)

  27. Some cytokines use a common chain for signal transduction

  28. 2. Soluble cytokine receptor

  29. PartⅣ Biological functions of cytokines 1.Take part in nonspecific immunity ------anti-bacteria, anti-virus 2. Take part in specific immunity 3. Stimulate hematopoiesis 4. Take part in inflammatory reaction

  30. PartⅤ Cytokine and disease • Cytokines and diagnosis: IL-3, CSF • Cytokines and treatment: Th1/Th2/Th9/Th17/Th22/Treg • Cytokines and disease prevention: CSF, IL-2 • Cytokine assay: ELISA, flow cytometry

  31. What should you know by the end of this lecture? • Definition of cytokine • General properties of cytokines • Classification and function of cytokines

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