医学免疫学英文教学课件：Chapter 7 cytokines

1、Chapter 7 Cytokines (CKs)Jianing Wang ContentsPart Definition and general properties of cytokinesPart Classification of cytokinesPart Cytokine receptorPart Biological functions of cytokinesPart Cytokine and diseasePart Definition and general properties of cytokines. Definition A group of low molecul

2、ar 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. General properties of cytokines1.Most cytokines are low m

3、olecular weight polypeptides or glycoprotein(880 KD), and most of them are monomer.2.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 IFN-,TNF- IL-4，6 IL-5 TH1TH2Natural cytokines are secreted by activated cells Such a

4、s activated immune cells,matrix cells and some tumor cells. 3. 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) afte

5、r being carried in blood or tissue fluids. Distance autocrine endocrineBlood circulation paracrine Nearby selfCytokines take effect in three ways 4.Cytokines initiate their actions by binding to specific membrane receptors on target cells.Receptors for cytokines often bind their ligands with high af

6、finities. 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.5. The effects of cytokines are often pleiotropism, redundant, synerg

7、y, antagonism, and form a cytokine network.Pleiotropism refers to the ability of one cytokine having multiple effects on diverse cell types.Redundancy refers to the property of multiple cytokines having the same or overlapping functional effects.Synergy refers to the property of two or more cytokine

8、s having greater than additive effects.Antagonism refers to the ability of one cytokine inhibiting the action of another.Th0ThpIL-12IL-4IL-2TNF-IFN-Th1Th2IL-10IL-4IL-5IL-13AgTH1MjIL- 4 骨髓基质细胞IL-1 IL-6 IL-7 SCF 造血干细胞IL-1 IL-6 IL-11 TNF-a GM-CSF G-CMF M-CSF单核细胞TH2B中性粒细胞嗜酸性粒细胞IL-1 IL-8 TNF-aIL-1 TNF-aI

9、L-10 IL- 4IL- 4 IL-6 IL-10 IL-13 IL-4 TGF-bIL-4 IL-5 IL-6 IL-13 IL-10 TGF-bIL-4IL-4内皮细胞IL-4TcIL-4IL-2 IFN-gIL-10 IL-13 IL-4 NK1+T NK 细胞IFN-gIL-2IL-2 IFN-gIL-2IL-2 IL-12G-CMF IFN-g GM-CSF IL-12IL-1 TNF-a TGF-b PDGF FGF M-CSF GM-CSF 内皮细胞纤维母细胞下 丘 脑IL-1 TNF-aM-CSF GM-CSF IL-1 IL-6 TNF-aIL- 4IL- 6IL- 4Pa

10、rt Classification of cytokines Interleukin, ILInterferon, IFNTumor necrosis factor, TNFColony stimulating factor, CSFChemokineTransforming growth factor. Interleukin (IL)Cytokines secreted by leukocytes that have the ability to act as signal molecules between different population of leukocytesIL-1IL

11、-35. Interferon (IFN) A group of glycoproteins that produced by human or animal cells following the infection of virus and exposure to various inducing agents Comparison of IFN-, IFN-, IFN-_ Types Produced cells Main functions _ IFN- leukocyte anti-virus,immune regulation IFN- fibroblast anti-tumor

12、IFN-Type II Th1,NK weaker anti-virus effect stronger immune regulation effect anti-tumor_Type I.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 macro

13、phages.TNF-(lymphotoxin, LT) is produced mainly by activated Th0 and Th1. . 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-C

14、SF)Granulocyte-CSF(G-CSF)Stem cell factor(SCF)Erythropoietin(EPO). Chemokine Chemokines are cytokines which recruiting monocytes, granulocytes and lymphocytes in blood to the sites of inflammation.CXC chemokines( subgroup):IL-8CC chemokines( subgroup):MCP-1C chemokines( subgroup)CX3C chemokines( sub

15、group)*C: cysteine; X: any amino acid. Transforming growth factor Growth-factor are cytokines which stimulate the growth of their target cells.Transforming growth factor-(TGF- )Epithelia growth factor(EGF)Vascular endothelia cell growth factor(VEGF)Fibroblastic growth factor(FGF) Part CK receptor1.

16、Membrane-binding cytokine receptors: The receptor consists of extra-cellular region, trans-membrane region and cytoplastic region. CK receptors can be grouped into five families according to structure and function:(1) Ig receptor superfamily:IL-1R,PDGFR,FGFR(2) Type CK receptor superfamily: CSFR(3)

17、Type CK receptor superfamily: IFNR(4) Type CK receptor superfamily: TNFR(5) G-protein linked receptor superfamily: CCR5 High affinity IL-2Rgbg baaLow affinity IL-2RModerate affinity IL-2RIL-2IL-2 receptorThree forms of the IL-2 Receptor(CD25)Some cytokines use a common chain for signal transduction2.soluble cytokine receptorPart Biological functions of cytokines1.Take part in nonspecific immunity -anti-bacteria, anti-virus 2. Take part in specific immunity3. St