细胞因子及其受体.ppt

,Historyfortheresearchofthecytokines,In1957，Interferon（IFN）wasfoundIn1969，termedlymphokineIn1974，denominatedcytokinecytokinology；internationalcytokinesocietyCytokineCompaniesfordevelopingcytokinesinmanycountries,Cytockinesarelow-molecular-weightregulatoryproteinsorglycoproteinssecretedbywhitebloodcellsandvariouscells(vascularendothelialcell,epidermiccellandfibroblast)inbodyinresponsetoanumberofstimuli.,Cytokine,由免疫细胞和某些非免疫细胞（如血管内皮细胞、表皮细胞和成纤维细胞等）经刺激而合成分泌的一类小分子量可溶性糖蛋白或蛋白多肽。,细胞因子(cytokine),Cytokinegene,Inducingstimulus,Cytokine-producingcell,Cytokine,Geneactivation,Receptor,signal,Biologicaleffects,OverviewoftheinductionandfunctionofCytokine,生物学效应：免疫细胞之间的信息交换及相互调节依赖于细胞因子。细胞因子除了介导、调节局部和全身免疫应答和炎症反应过程之外，还对伤口愈合、造血干细胞再生与分化密切相关。,-S-S-,-S-S-,-S-S-,CCCC,C1C3C2,C1C3C2,C1C3C2,C1C3C2,G蛋白,细胞因子受体,Biologicaleffects：Regulationandtransferoftheinformationbetweentheimmunecells;Mediationandregulationoftheimmuneresponseandinflammation;Relationshipwiththewoundhealing,theregenerationanddifferentiationofthehemopoieticstemcells,-S-S-,-S-S-,-S-S-,CCCC,C1C3C2,C1C3C2,C1C3C2,C1C3C2,G蛋白,cytokinereceptors,Biologicaleffectsofthecytokines,Anti-infectionandantitumorImmuneregulationapoptosisStimulatingtheproliferationanddifferentiationofhemopoieticstemcellsPromotethegrowthanddifferentiationofvariouscellsParticipationandregulationoftheinflammatoryresponsesCytokineabnormalitiesinthepathogenesisincertaindiseasesParticipationofthenever-endocrine-immunitynet,细胞因子的主要生物学效应,抗感染和抗肿瘤作用免疫调节作用参与细胞凋亡刺激造血细胞增埴分化促进各种细胞的生长和分化参与和调节炎症反应细胞异常可导致疾病的发生参与神经-内分泌-免疫网络,参与免疫应答与免疫调节免疫应答识别（感应）阶段IFN刺激APCMHC-II的表达IL-1辅助T细胞活化IL-10抑制抗原递呈免疫应答细胞扩增阶段IL-2、IL-4、IL-5、IL-6等促进T、B细胞的增殖与分化TGF-b抑制淋巴细胞增殖,参与神经-内分泌-免疫网络细胞因子对神经内分泌：IL-1、IL-6、TNF等直接参与神经系统的正常发育和损伤修复IL-1、TNF、IFN-g、PAF等诱导垂体释放ACTH，进而促进肾上腺皮质激素的释放应激时儿茶酚氨和糖皮质类固醇分泌增多，进而抑制IL-1、TNF的合成。在免疫应答过程中，免疫细胞之间通过细胞因子相互刺激、彼此约束，对免疫应答进行调节，维持免疫系统的稳态平衡。,1.白细胞介素(interleukin,IL)2.集落刺激因子（colonystimulatingfactor,CSF).3.干扰素（interferon,IFN)4.肿瘤坏死因子（tumornecrosisfactor,TNF)5.趋化因子（chemokine)6.生长因子(growthfactor,GF),细胞因子的种类,Interleukin,ILinterleukinsaresecretedbysomeleukocytesandactuponotherleukocytes,IL-1IL-23havebeenidentified.Colonystimulatingfactor,CSFThecytokinesthatstimulatehemopoieticcellstoformcellcolony,ParticipatehemopoieticfunctionarecalledCSF,forexampleGM-CSF,G-CSF,M-CSF,Epo,Tpo,GM-CSF,具有干细胞集落刺激活性的细胞因子,主要产生细胞,作,用,SCF,纤维母细胞，肝细胞，内皮细胞，,上皮细胞，基质细胞,所有类型的造血干细胞，黑色素,细胞，肥大细胞,IL-3,T,细胞,中性粒细胞，单核细胞，红细胞，,嗜碱性粒细胞,IL-5,T,细胞,嗜酸性粒细胞,IL-11,基质细胞，纤维母细胞,所有类型的造血干细胞，血小板,GM-CSF,T,细胞，单核细胞，内皮细胞，纤,维母细胞,中性粒细胞，单核细胞，嗜酸性,粒细胞，树突细胞,G-CSF,单核细胞，纤维母细胞，,中性粒细胞,M-CSF,单核细胞，淋巴细胞，纤维母细胞，,内皮细胞，上皮细胞,单核细胞，胎盘滋养细胞,EPO,肾脏细胞,红细胞,TPO,肾，肝,血小板,集落刺激因子的作用,Interferon,IFNthecytokinesthatresistviralinfection,andinterfereviralreplication,includingIFN,IFN(typeI);IFN(typeII)Tumornecrosisfactor,TNFthecytokinesthatinducedirectlyapoptosisoftumorcells,includingTNF,TNF(Lymphotoxin,T）,FASL,CD70L,CD30L,CD40L,OX40L,TRAIL(TNFrelatedapoptosis-inducingligand,Growthfactorthecytokinesthatpromotegrowthofvariouscells,epidermalgrowthfactor，insulin-likegrowthfactor，vascularendothelialgrowthfactorChemokinechemokines,agroupoflow-molecular-weightcytokinwsincludinginterleuki8,thataffectchemotaxisandotheraspectsofleukocytebehavior.,Chemokinecausesthecellularmorphologicalteration,11-1mainpropertiesofthecytokines,autocrine,endocrine,Bindingtotargetcellsindistantpartsofthebody.,paracrine,Bindingtoreceptorsonatargetcellincloseproximitytotheproducercells,1.actionmanners,Bindtoreceptorsonthemembraneofthesamecellthatsecretedit,肥大细胞,胸腺细胞,B,IL-4,活化、增殖、分化,增殖,增殖,2.多效性pleiotropy,IL-2、IL-4、IL-5,IL-4+IL-5,B细胞,IL-4,IFN-,5.拮抗性antagonism,3.重叠性redundancy,4.协同性synergy,均有刺激B细胞增殖的功能,更有效地诱导IgE类别转换,IL-4阻断IFN-诱导类别转化的作用,B,B,B,Onstimulation,rapidsynthesis,release,actionanddegragation.,6.rapidity,7.highpotency,Infinitesimalcytokinesperformremarkablebiologicaleffects（pM,10-12M).,细胞因子受体,免疫球蛋白超家族（IgsF）造血细胞因子受体超家族（HCKRsF）趋化因子受体超家族（ChRsF）TFN受体超家族（TNFRsF）IFN受体家族,Solublecytokinereceptors(sCKR),Producingmatter:MostofthembreakofffromthememberreceptorsSecretereceptor,IL-1IL-6IL-12和IL-18TNF,11-2Thecytokinesproducedbymacrophages,1.activatingTcells2.stimulatingproliferationofBcellandantibodysecreting3.inducingacutephaseresponseofliver4.inducingmacrophageactivation5.trigginginflammationandfever6.stimulatingregenerationofhemopoieticstemcells,ThefunctionsofIL-1,macrophage,IL-1,TNF-a157aa,tumornecrosisfactor,TNF,Twotypes:,TNF-a,TNF-b(lymphotoxin-a,LT-a),TNF-b=LTa171aa,Activatedmacrophage,Homology28%SamereceptorsSamebioactivities,ActivatedTcell,Up-regulationofthecytokineproduction(IL-2,IL-4,gIFN,CSF)andexpressionofIL-2receptor,TNF-a,Inducingdifferentiationup-regulationofantibodyproduction,Up-regulationofproductionprostaglandinandcytokines(IL-1,IL-6,IL-8,GM-CSF),Chemotaxisandactivationofneutrophil,StimulatingproductionofCSFUp-regulationofhemopoiesis,BioactivitiesofTNF-a,11-3cytokineproducedbyTcells,IL-2,IFN-gIL-4IL-5IL-10,Th1和Th2细胞的分化,Th1-Th2分泌细胞因子的相互调节及其效应,B细胞,IgG2a,Tc细胞活化,巨噬细胞活化,B细胞,IgM，IgG1，IgA，IgE,肥大细胞生长,嗜酸性粒细胞生长与分化,B细胞，巨噬细胞,Th2细胞，肥大细胞,IL-12,IL-4,IL-10,IFN-g,Th1,IFN-g,IL-12,IL-4,IL-110,IL-13,IL-2,IFN-g,TNF-b,IL-12,IL-3IL-4,Th2,IL-10,IL-5,IL-4,ImmunebioactivitiesofIL-2,IL-1,g-IFNIL-4IL-5IL-6,Th1,Th1,APC,Mj,呈递抗原,抗原,活化T细胞（IL-2产生的前体细胞）,Th1,增殖分化并分泌抗体,Th1,Th1,B,抗原刺激,分化,复制,IL-2反应细胞（TH或TC细胞）,IL-2的生物学作用,IL-1,g-IFNIL-4IL-5IL-6,Th1,Th1,APC,Mj,Antigenpresentation,antigen,ActivationofTcell(precursorproducingIL-2）,Th1,proliferation,differentiationSecretionofantibody,Th1,Th1,B,antigen,differentiation,replication,IL-2reactivecells（ThorTC）,ImmunebioactivitiesofIL-2,TypeIinterferon：IFN-,IFN-anti-virus,TypeIIinterferon:IFN-,immuneregulation,in