chapter-11-CYTOKINE-AND-CYTOKINE-RECEPTOR-forclass

Chapter11Mastertheconceptandclassificationofthecytokines;MasterthemainpropertiesandBiologicaleffectsofthecytokines;KnowthemainpropertiesandfunctionofIFN,TNF,ILandCSF;Understandthecytokinereceptors.HistoryfortheresearchofthecytokinesIn1974，denominatedcytokinecytokinology；internationalcytokinesociety《Cytokine》CompaniesfordevelopingcytokinesinmanycountriesIn1957，Interferon（IFN）wasfoundIn1969，termedlymphokineMjmacrophageIL-1ActivatedTh1cellDNH2COOHIL-2Cytockinesarelow-molecular-weightregulatoryproteinsorglycoproteinssecretedbywhitebloodcellsandvariouscells(vascularendothelialcell,epidermiccellandfibroblast)inbodyinresponsetoanumberofstimuli.CytokineCytokinegeneInducingstimulusCytokine-producingcellCytokineGeneactivationReceptorsignalBiologicaleffectsOverviewoftheinductionandfunctionofCytokineSection1Commoncharacteristicsofcytokines1Mechanismsoffunction(1)BindingtospecificreceptorsandperformanceautocrineendocrineCirculationBindingtotargetcellsindistantpartsofthebody.paracrineBindingtoreceptorsonatargetcellincloseproximitytotheproducercells(2)ActionmannersBindtoreceptorsonthemembraneofthesamecellthatsecreteditMastcellThymuscellBIL-4Activationproliferationdifferentiationproliferationproliferation(1)Pleiotropy(多效性)2ComplexityofactionsIL-2、IL-4、IL-5IL-4+IL-5IL-4IFN-(4)Antagonism拮抗性(2)Redundancy重叠性(3)Synergy协同性StimulatingtheproliferationoftheBcellsMoreeffectivelyinducingtheexchangeofIgEIL-4interdictstheactionthatIFN-inducesIgexchangesBBB_+Onstimulation,rapidsynthesis,release,actionanddegradation.3Rapidity1.interleukin,IL2.colonystimulatingfactor,CSF3.interferon,IFN4.tumornecrosisfactor,TNF5.chemokineCK6.growthfactor,GFSection2ClassificationandfunctionofcytokinesIL-13IL-2IL-4Interleukinsaresecretedbysomeleukocytesandactuponotherleukocytes,IL-1~IL-35havebeenidentified.1Interleukin,ILThecytokinesthatresistviralinfection,andinterfereviralreplication,includingIFN,IFN(typeI);IFN(typeII)2Interferon,IFNviruscellinfectionIFN-,IFN-IFNIFNTheanti-virusmechanismofIFN-virusviralreplicationInhibitionofviralreplicationSignal-transductionIFN-IFN-inducedproteinstimulatingnuclearnuclear3Tumornecrosisfactor,TNFThecytokinesthatinducedirectlyapoptosisoftumorcells,includingTNF,TNF(Lymphotoxin,LT）,FASL,CD70L,CD30L,CD40L,OX40L,TRAIL(TNFrelatedapoptosis-inducingligand)TNF-BiologicalactivitiesofTNF-.Acanceroustumorinamouseinjectedwithendotoxin(left)showshemorrhagicnecrosis,unlikeatumorinanuntreatedmouse(right).EndotoxininducestheproductionofTNF-,whichthenactstodestroythetumor.Transgenicmouse(top)bearingaTNF-transgenebecomesanorecticandseverelywasted.Normalmouseisshownonthebottom.4Colonystimulatingfactor,CSFThecytokinesthatstimulatehemopoieticcellstoformcellcolony,ParticipatehemopoieticfunctionarecalledCSF,forexampleGM-CSF,G-CSF,M-CSF,Epo(erythropoietin),Tpo(thrombopoietin).G-CSFGM-CSFThefunctionsofCSFThecytokinesthatpromotegrowthofvariouscells,epidermalgrowthfactor，insulin-likegrowthfactor，vascularendothelialgrowthfactor5Growthfactorvascularendothelialgrowthfactor(VEGF)GrowthfactorsappliedtoangiogenesisVEGFpromotesTumorAngiogenesisVEGFpromotesTumorAngiogenesis6Chemokinechemokines,agroupoflow-molecular-weightcytokinwsincludinginterleuki8,thataffectchemotaxisandotheraspectsofleukocytebehavior.StromalDerivedFactor-1SolutionStructureOfTheCx3CChemokineDomainOfFractalkineCytokinespossessingchemotaxisC5acytokine（IL-8)ChemokinemaketheshapesofcellschangedmemberreceptorsSecretereceptorSection3CytokinereceptorSection4Biologicaleffectsofcytokines1Regulateimmunocytedifferentiationandmaturation2Mediateinnateimmunity3Mediateadaptiveimmunity4Stimulatehaematogenesis5CytokineandtumorTheroleofIL-8signalinginthetumormicroenvironment.Tumor-derivedIL-8hasthecapacitytoexertprofoundeffectsonthetumormicroenvironment.Forexample,secretionofIL-8fromcancercellscanenhancetheproliferationandsurvivalofcancercellsthroughautocrinesignalingpathways.Inaddition,tumor-derivedIL-8willactivateendothelialcellsinthetumorvasculaturetopromoteangiogenesisandinduceahemotacticinfiltrationofneutrophilsintothetumorsite.AlthoughIL-8canpromotecellinvasionandmigration,thecapacityofIL-8toinducetumor-associatedmacrophagestosecreteadditionalgrowthfactorswillfurtherincreasetherateofcellproliferationandcancercellinvasionatthetumorsite.6Cytokinesandimmunologicaldisorders(1)TransplantationrejectionX-linkedSCID,(XSCID)(2)ImmunodeficiencyMutationsinthec(commonchain)chainofthereceptorsforinterleukinsIL-2,-4,-7,-9and-15**Signaltransduction,**lymphocytedifferentiation,proliferationandmaturationIL-2RIL-4RIL-7RIL-9RIL-15RcommonchainInthe1990s,lateresearcherstestedagenetherapytreatmentthatwouldrestorethefunctionofacrucialgene,gammac,tocellsoftheimmunesystem.Thistreatmentappearedverysuccessful,restoringimmunefunctiontomostofthechildrenwhoreceivedit.bubbleboydisease,有γ链细胞因子受体图解含有γ链的细胞因子受体损伤或缺失导致下游信号传导受阻引起SCID病。γ链是IL-2、IL-4、IL-7、IL-9、IL-15和IL-21受体的组成成分。其中，IL-2R、IL-15R有三个亚基：α、β、γ；IL-4R、IL-7R、IL-9R和IL-21R由α、γ亚基组成。若没有γ链，正常信号传导途径--JAKs激活、信号使者磷酸化、STAT蛋白激活受阻。至今研究确定SCID的起因包括γ链损伤和表达的γ链无功能、表达的JAK