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1、8-30KD CK-CKRs,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,macrophage,Just as hormones serve as messenger of t
2、he endocrine system, so cytokine sever as messengers of the immune system. Unlike endocrine hormones , though, which exert their effects over large distances, cytokines general act locally.,Cytokines can exert different actions,IL-2 Proliferation, survival,Example:,Chemokines Leukocyte recruitment,A
3、cute phase proteins, IL-6 TNF IL-33,Properties of cytokines,细胞因子调节IgG类别转换,多效性,拮抗性,重叠性,协同性,Biological effects of the cytokines,Anti-infection and antitumor Immune regulation Apoptosis Stimulating the proliferation and differentiation of hemopoietic stem cells Promote the growth and differentiation of
4、 various cells Participation and regulation of the inflammatory responses Cytokine abnormalities in the pathogenesis in certain diseases,Cytokines during hematopoiesis,interleukin, IL （白细胞介素） colony stimulating factor,CSF（集落刺激因子） interferon,IFN（干扰素） tumor necrosis factor,TNF （肿瘤坏死因子） Chemokine, CK （
5、趋化因子） growth factor,GF （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 infectio
6、n 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 by macrophages induces local protect
7、ive effects, but TNF-a can have damaging effects when released systemically (septic shock).,Tumor necrosis factor,TNF,The cytokines that induce directly apoptosis of tumor cells, including TNF, TNF (Lymphotoxin, LT） , FASL, CD70L, CD30L, CD40L, OX40L, TRAIL (TNF related apoptosis-inducing ligand),Ch
8、emokine,chemokines, a group of low-molecular-weight cytokines including interleukin 8, that affect chemotaxis and other aspects of leukocyte behavior.,1999年国际命名委员会根据CK的结构特征命名 依据N端前两个半胱氨酸(Cys)的相对位置不同分为:,IL-12 produced by macrophages and dendritic cells is a key cytokine to fight intracellular microbe
9、s (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 IFN, IFN, I
10、FN, IFN, IFN ( type I ); IFN ( type II ),type I Interferon,Antiviral effects of Type I Interferons (IFN-a/b),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 differentita
11、tion factor IFN-: inducer of Th1 cells,IL-2 (又称T细胞生长因子,TCGF) ： 细胞来源：主要由T细胞产生。 作用方式：以自分泌和旁分泌方式发挥效应。 主要生物学功能： （1）活化T细胞，促进细胞因子产生； （2）刺激NK细胞增殖，增强NK杀伤活性及产生 细胞因子；诱导LAK细胞产生 （3）促进B细胞增殖和分泌抗体； （4）激活巨噬细胞。,IL-4 induces Isotype switching against extracellular pathogens, such as helminths and athropodes,IL-4,Plei
12、otropic 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 cy
13、tokines,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
14、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 stimulat
15、es 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, C
16、SF,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。 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（epidermal growth factor, EGF) 血管内皮生长因子（vascular endothelial growth factor, VEGF) 成纤维细胞生长因子（fibroblast growth factor, FGF) 神经生长因子(nerve growth factor, NGF) 血小板衍生的生长因子（platelet derived growth factor, PDGF) 肝细胞生长因子（hepatic growth factor, HGF),Growth factor,VEG
