博士生课程5(1)-细胞因子.ppt

8 8-30KD30KD CKCK-CKRsCKRs Cytockines are low-molecular-weight regulatory proteins or glycoproteins secreted by white blood cells and various cells(vascular endothelial cell,epidermic cell and fibroblast)in body in response to a number of stimuli.Cytokine Mj macrophagemacrophage IL-8 Cytokines can exert different actions IL-2 Proliferation,survival Example:Chemokines Leukocyte recruitment Acute phase proteins,IL-6 TNF IL-33 Properties of cytokines 细胞因子调节IgG类别转换 多效性多效性 拮抗性拮抗性 重叠性重叠性 协同性协同性 Cytokines during hematopoiesis interleukin,IL（白细胞介素）（白细胞介素）colony stimulating factor,CSF（集落刺激因子）（集落刺激因子）interferon,IFN（干扰素）（干扰素）tumor necrosis factor,TNF（肿瘤坏死因子）（肿瘤坏死因子）Chemokine,CK（趋化因子）（趋化因子）growth factor,GF（生长因子）（生长因子）Cytokines Cytokines of the innate and adaptive immune system Cytokines of innate immune system TNF,IL-1 and IL-6:pleiotropic mediators of inflammation(activators of endothelium,immune cells,liver and brain)Chemokines:regulators of immune cell adhesion at infection sites IL-12:inducer of IFN-,increase of cytotoxic activity Type I IFN:inducers of antiviral state Interleukin Interleukins are secreted by some leukocytes and act upon other leukocytes,IL-1IL-35 have been identified.Interleukin-1,IL-1 The release of TNF-a a by macrophages induces local protective effects,but TNF-a a can have damaging effects when released systemically(septic shock).Tumor necrosis factor,TNF The cytokines that induce directly apoptosis of tumor cells,including TNFa a,TNF (Lymphotoxin,LT）,FASL,CD70L,CD30L,CD40L,OX40L,TRAIL(TNF related apoptosis-inducing ligand)Chemokine chemokines,a group of low-molecular-weight cytokines including interleukin 8,that affect chemotaxis and other aspects of leukocyte behavior.CX3CR CXCR CX3C CXC CK及及CKR分类分类 CC C CCR XCR 1999年国际命名委员会根据年国际命名委员会根据CK的结构特征命名的结构特征命名 依据依据N端前两个半胱氨酸端前两个半胱氨酸(Cys)的相对位置不同分为的相对位置不同分为:IL-12 produced by macrophages and dendritic cells is a key cytokine to fight intracellular microbes(bacteria and viruses)IL-12 induces IFN-,an activator of macrophages(killing of phagocytosed microbes)and Th1 cell differentiation IL-12 also increases cytotoxic activity of CD8 and NK cells IL-12 The cytokines that resist viral infection,and interfere viral replication,including IFNa a,IFN,IFN,IFN,IFN(type I);IFN (type II)type I Interferon Antiviral effects of Type I Interferons(IFN-a a/)Integrative signaling of cytokines during innate immune responses Cytokines of adaptive immune system IL-2:prototypic lymphocyte growth factor IL-4:inducer of Th2 cells,B cell differentitation factor IFN-:inducer of Th1 cells ILIL-2(2(又称又称T T细胞生长因子细胞生长因子,TCGF),TCGF)：细胞来源：细胞来源：主要由主要由T T细胞产生。细胞产生。作用方式：作用方式：以自分泌和旁分泌方式发挥效应。以自分泌和旁分泌方式发挥效应。主要生物学功能：主要生物学功能：（1 1）活化）活化T T细胞，促进细胞因子产生；细胞，促进细胞因子产生；（2 2）刺激）刺激NKNK细胞增殖，增强细胞增殖，增强NKNK杀伤活性及产生杀伤活性及产生 细胞因子；诱导细胞因子；诱导LAKLAK细胞产生细胞产生 （3 3）促进）促进B B细胞增殖和分泌抗体；细胞增殖和分泌抗体；（4 4）激活巨噬细胞。）激活巨噬细胞。IL-4 induces Isotype switching against extracellular pathogens,such as helminths and athropodes IL-4 Pleiotropic activities of IFN-IFN-is secreted by activated T cells after IL-12 stimulation during antimicrobial responses(intracellular bacteria and viruses)Th1 cells help B cell sotype switch to IgG for complement binding and Fc-binding on phagocytes strong macrophage activator Anti-inflammatory cytokines IL-10 IL-10:counteracts IFN-by blocking IL-12 production by macrophages,and expression of costimulators and MHC II IL-10-deficient mice develop inflammatory bowel disease Tr1 TGF-TGF-is secreted by regulatory T cells(Th3)to decrease immune responses The TGF receptor is a dimer of ALK and TGF-RII which signal through Smad transcription factors Absence of TGF or TGF-RII induces autoimmunity in mice Additional key cytokines IL-5:activator of eosinophils,also inducing production of additional eosinophils from bone marrow progenitors IL-13:similar to IL-4,but in addition stimulates mucus production and tissue fibrosis in allergic diseases GM-CSF:promotes maturation of bone marrow cells to monocytes and dendritic cells G-CSF:generated at site of infection but acting as endocrine hormone to mobilize neutrophils during inflammation(clinical use)Colony stimulating factor,CSF The cytokines that stimulate hemopoietic cells to form cell colony,Participate hemopoietic function are called CSF,for example GM-CSF,G-CSF,M-CSF,Epo,Tpo 是一类可介导不同类型细胞生长和分化的细胞因子。是一类可介导不同类型细胞生长和分化的细胞因子。根据其功能和作用的靶细胞不同，分别命名为：根据其功能和作用的靶细胞不同，分别命名为：表皮生长因子（表皮生长因子（epidermal growth factor,EGF)血管内皮生长因子（血管内皮生长因子（vascular endothelial growth factor,VEGF)成纤维细胞生长因子（成纤维细胞生长因子（fibroblast growth factor,FGF)神经生长因子神经生长因子(nerve growth factor,NGF)血小板衍生的生长因子（血小板衍生的生长因子（platelet derived growth factor,PDGF)肝细胞生长因子（肝细胞生长因子（hepatic growth factor,HGF)Growth factor VEGF Receptor Signaling Growth factors applied to angiogenesis VEGF promotes Tumor Angiogenesis TH1 and TH2 subsets secrete different cytokines TH1-cell-mediated functions;inflammation TH2-humoral immunity TH1 and TH2 subsets regulate each other CD4+T cells isolation and differentiation Spleens were mechanically diss