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1、 Introduction of Cytokines Classification of CKs Biological Activities of CKs Cytokine Receptor (CKR) Clinical Application of CKs,Cytokines,细胞因子,Chapter 5,1,.Introduction of cytokine (CK),A.Biological properties B.Secretory feature C.CKs network,1.Conception of CK,2.Common properties of CKs,-由免疫细胞及非
2、免疫细胞 经刺激而合成、分泌的一类具有多 种生物活性的小分子蛋白质,2,A.Biological properties, Low molecular-weight protein or glycoprotein (MW 15 30KD) Monomer, dimer or trimer Rapid reactivity and high efficiency (CK binding to CKR) Nonspecific and non-MHC restriction,3,B.Secretory feature, Transient and self-restraint Autocrine a
3、nd paracrine Endocrine,(also called immunohormone),4,C. CKs networks, Multicellular sources, TIL2-6,9,10,13 T,Mo/MIL-1,6,10,GM-CSF, pleiotropy (多效性) IFN- overlapping（重叠性） IL-2,4,7,9,12 two-way effects (双向性) TNF, Complexity of biological effects, Synergy & antagonism, synergy IL1 and IL-4 antagonism
4、IFN- and TGF-,5,重叠性 IL-2,4,7,9,12 T细胞增殖,双向性 抗肿瘤 适量 TNF 过量 BSS (细菌性脓毒 血症休克),协同作用 IL-1 IL-4 B 细胞增殖,拮抗作用 IFN- + LAK细胞增殖 TGF-,多效性,IFN-,LAK,B,Th2,NK,增殖,分化,分泌活性,杀伤活性,(IL-1 + IL-4),6,1.Interleukin (IL),A.IL-1 to IL-22 B.Biologic effects, activate immune cells take part in immunoregulation, hematopoiesis an
5、d inflammation reaction,白细胞介素是一组由由淋巴细胞或其他单个核細胞产生的介导白细胞间相互作用的细胞因子,也参与其他细胞的相互作用,.Classification of CKs,7,2.Interferon (IFN),A. IFN-/ (type) and IFN- (type ) B.Biologic effects, antivirus anti-tumor immunoregulation,具有干扰病毒复制能力的细胞因子,故称干扰素,8,3. Tumor necrosis factor (TNF),Anti-tumor Take part in inflamma
6、tion and endotoxic shock Regulate IR,A.TNF- and TNF-,B. Biologic effects,(双向效应),(内分泌,恶液质素),(lymphotoxin, LT),(homological trimer),一类能引起肿瘤组织出血坏死的细胞因子,故称为肿瘤坏死因子,(直接杀死肿瘤细胞),9,4. Colony stimulating factor (CSF),kinds :G-CSF,M-CSF,GM-CSF, multi- CSF (IL-3 ), SCF, EPO,TPO and so on.,-是一类可选择性刺激造血干细胞增殖 分化为某
7、一谱系细胞集落的细胞因子,10,5.Growth factor (GF),A.EGF,NGF,VEGF,PDGF and TGF-,B.IL-2 and TNF, proliferation of lymphocytes maturation of CTL activation of M cytotoxicity of CTL and NK cell,immune suppress,-一类能介导不同类型细胞生长和分化的CKs,11,6. Chemokine,-一类对不同靶细胞具有趋化效应的CK家族,CXC/ chemokine CC/ chemokine C/ chemokine,MCP (单
8、核细胞趋化蛋白) MIP (巨噬细胞炎症蛋白),lymphotactin (淋巴细胞趋化蛋白),新近报道还有CX3C/ chemokine,IL-8,12,. Biological Activities of CytoKines,1.Anti-infection and anti-tumor,A.direct effects B.by means of activating effector cells,IFN- / , IL-12,IL-15 (anti-virus) IL-1,6,8 and TNF (anti-bacteria) TNF,IFN (anti-tumor),IL-2,12
9、and IFN- NK cell IL-12 ,TNF and IFN- M,13,2.Mediate and regulate immune response,识别阶段增生和分化阶段效应阶段,APC表达 MHC- 类分子,IFN-,IL-2 IL-4,5,6,T细胞 B细胞 活化增生和分化,IFN- / IL- 12, 15,抗病毒感染,IL-1,6,8; TNF-,抗菌感染,IL-10,Ag提呈,TGF-,Th1 Th2 IFN- ,IL-2 IL-4,5,6 细胞免疫 B细胞体液免疫 (CTL,M,NK cell),IFN-,IL-4,10,TNF -,IFN,IL-2 CTL M,NK
10、活性,正调节,负调节,14,3.Stimulating hematopoiesis,HSC,4. Induce apoptosis,(CK可直接或间接诱导细胞凋亡),15,.Cytokine Receptor (CKR),1. Classification of CKR,mCKR,sCKR(可溶性CKR),干,型CKR超家族,型CKR超家族,型CKR超家族 TNF受体,型CKR超家族,趋化性CKR超家族,CCR,CXCR,CR,CX3CR,(CCR5,CXCR4 为HIV 辅助受体),16,2. Multisubunits receptor,-CKR consists of 2 or over
11、 2 subunits,CK-binding subunit(即特异性配体结合链) signal transduction subunit,-often is common subunit of CKs (i.e. common signal transduction subunit),17,. Clinical Application of CKs,1.Infectious diseases 2. Hemocytopenia 3. Tumor 4. Autoimmune diseases 5.Hypersensitivity and rejection of graft,IL-1,TNFBSS* treat IL-1Ra and anti-TNF (mAb),LAK and CIK*,*BSS -(bacterial septic shock, 细菌性脓毒血症休克),*LAK(lymphokine activated killers) IL-2 CIK(cytokine induced killers ) (IL-1,IL-2,IFN)+anti-CD3 mAb,18,
