細胞因子及其受體

細胞因子及其受體Cytockinesarelow-molecular-weightregulatoryproteinsorglycoproteinssecretedbywhitebloodcellsandvariouscells(vascularendothelialcell,epidermiccellandfibroblast)inbodyinresponsetoanumberofstimuli.

Cytokine由免疫細胞和某些非免疫細胞（如血管內(nèi)皮細胞、表皮細胞和成纖維細胞等）經(jīng)刺激而合成分泌的一類小分子量可溶性糖蛋白或蛋白多肽。細胞因子(cytokine)CytokinegeneInducingstimulusCytokine-producingcellCytokineGeneactivationReceptorsignalBiologicaleffectsOverviewoftheinductionandfunctionofCytokine生物學效應(yīng)：免疫細胞之間的信息交換及相互調(diào)節(jié)依賴于細胞因子。細胞因子除了介導(dǎo)、調(diào)節(jié)局部和全身免疫應(yīng)答和炎癥反應(yīng)過程之外，還對傷口愈合、造血干細胞再生與分化密切相關(guān)。-S-S--S-S--S-S-CC

CCC1C3C2C1C3C2C1C3C2C1C3C2G蛋白細胞因子受體Biologicaleffects：

Regulationandtransferoftheinformationbetweentheimmunecells;Mediationandregulationoftheimmuneresponseandinflammation;Relationshipwiththewoundhealing,theregenerationanddifferentiationofthehemopoieticstemcells-S-S--S-S--S-S-CC

CCC1C3C2C1C3C2C1C3C2C1C3C2G蛋白cytokinereceptorsBiologicaleffectsofthecytokinesAnti-infectionandantitumorImmuneregulationapoptosisStimulatingtheproliferationanddifferentiationofhemopoieticstemcellsPromotethegrowthanddifferentiationofvariouscellsParticipationandregulationoftheinflammatoryresponsesCytokineabnormalitiesinthepathogenesisincertaindiseasesParticipationofthenever--endocrine-immunitynet細胞因子的主要生物學效應(yīng)抗感染和抗腫瘤作用免疫調(diào)節(jié)作用參與細胞凋亡刺激造血細胞增埴分化促進各種細胞的生長和分化參與和調(diào)節(jié)炎癥反應(yīng)細胞異?？蓪?dǎo)致疾病的發(fā)生參與神經(jīng)-內(nèi)分泌-免疫網(wǎng)絡(luò)參與免疫應(yīng)答與免疫調(diào)節(jié)

免疫應(yīng)答識別（感應(yīng)）階段

IFN刺激APCMHC-II的表達 IL-1輔助T細胞活化 IL-10抑制抗原遞呈免疫應(yīng)答細胞擴增階段

IL-2、IL-4、IL-5、IL-6等促進T、B細胞的增殖與分化 TGF-b抑制淋巴細胞增殖參與神經(jīng)-內(nèi)分泌-免疫網(wǎng)絡(luò)

細胞因子對神經(jīng)內(nèi)分泌：IL-1、IL-6、TNF等直接參與神經(jīng)系統(tǒng)的正常發(fā)育和損傷修復(fù) IL-1、TNF、IFN-g、PAF等誘導(dǎo)垂體釋放ACTH，進而促進腎上腺皮質(zhì)激素的釋放 應(yīng)激時兒茶酚氨和糖皮質(zhì)類固醇分泌增多，進而抑制IL-1、TNF的合成。 在免疫應(yīng)答過程中，免疫細胞之間通過細胞因子相互刺激、彼此約束，對免疫應(yīng)答進行調(diào)節(jié)，維持免疫系統(tǒng)的穩(wěn)態(tài)平衡。1.白細胞介素(interleukin,IL)2.集落刺激因子（colonystimulatingfactor,CSF).3.干擾素（interferon,IFN)4.腫瘤壞死因子（tumornecrosisfactor,TNF)5.趨化因子（chemokine)6.生長因子(growthfactor,GF)細胞因子的種類Interleukin,ILinterleukinsaresecretedbysomeleukocytesandactuponotherleukocytes,IL-1~IL-23havebeenidentified.Colonystimulatingfactor,CSFThecytokinesthatstimulatehemopoieticcellstoformcellcolony,ParticipatehemopoieticfunctionarecalledCSF,forexampleGM-CSF,G-CSF,M-CSF,Epo,Tpo,GM-CSF

具有干細胞集落刺激活性的細胞因子

主要產(chǎn)生細胞作

用SCF纖維母細胞，肝細胞，內(nèi)皮細胞，上皮細胞，基質(zhì)細胞所有類型的造血干細胞，黑色素細胞，肥大細胞IL-3T細胞中性粒細胞，單核細胞，紅細胞，嗜堿性粒細胞IL-5T細胞嗜酸性粒細胞IL-11基質(zhì)細胞，纖維母細胞所有類型的造血干細胞，血小板GM-CSFT細胞，單核細胞，內(nèi)皮細胞，纖維母細胞中性粒細胞，單核細胞，嗜酸性粒細胞，樹突細胞G-CSF單核細胞，纖維母細胞，中性粒細胞M-CSF單核細胞，淋巴細胞，纖維母細胞，內(nèi)皮細胞，上皮細胞單核細胞，胎盤滋養(yǎng)細胞EPO腎臟細胞紅細胞TPO腎，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，vascularendothelialgrowthfactorChemokine

chemokines,agroupoflow-molecular-weightcytokinwsincludinginterleuki8,thataffectchemotaxisandotheraspectsofleukocytebehavior.Chemokinecausesthecellularmorphologicalteration11-1mainpropertiesofthecytokinesautocrineendocrineCirculationBindingtotargetcellsindistantpartsofthebody.paracrineBindingtoreceptorsonatargetcellincloseproximitytotheproducercells1.actionmannersBindtoreceptorsonthemembraneofthesamecellthatsecretedit肥大細胞胸腺細胞BIL-4活化、增殖、分化增殖增殖2.多效性pleiotropyIL-2、IL-4、IL-5IL-4+IL-5B細胞IL-4IFN-5.拮抗性antagonism3.重疊性redundancy4.協(xié)同性synergy均有刺激B細胞增殖的功能更有效地誘導(dǎo)IgE類別轉(zhuǎn)換IL-4阻斷IFN-誘導(dǎo)類別轉(zhuǎn)化的作用BBBOnstimulation,rapidsynthesis,release,actionanddegragation.6.rapidity7.highpotencyInfinitesimalcytokinesperformremarkablebiologicaleffects（pM,10-12M).

細胞因子受體免疫球蛋白超家族（IgsF）造血細胞因子受體超家族（HCKRsF）趨化因子受體超家族（ChRsF）TFN受體超家族（TNFRsF）IFN受體家族

Solublecytokinereceptors(sCKR)Producingmatter:

Mostofthembreakofffromthememberreceptors

SecretereceptorIL-1IL-6IL-12和IL-18TNF11-2Thecytokinesproducedbymacrophages1.activatingTcells2.stimulatingproliferationofBcellandantibodysecreting3.inducingacutephaseresponseofliver4.inducingmacrophageactivation5.trigginginflammationandfever6.stimulatingregenerationofhemopoieticstemcellsThefunctionsofIL-1MjmacrophageIL-1TNF-a157aatumornecrosisfactor,TNFTwotypes:TNF-a

TNF-b(lymphotoxin-a,LT-a)TNF-b=LTa171aaActivatedmacrophageHomology28%SamereceptorsSamebioactivitiesActivatedTcellIL-2IL-4

g-IFNUp-regulationofthecytokineproduction(IL-2,IL-4,g–IFN,CSF)andexpressionofIL-2receptorTNF-aBonemarrowInducingdifferentiationup-regulationofantibodyproductionUp-regulationofproductionprostaglandinandcytokines(IL-1,IL-6,IL-8,GM-CSF)ChemotaxisandactivationofneutrophilStimulatingproductionofCSFUp-regulationofhemopoiesisBioactivitiesofTNF-aBcellneutrophilMjmacrophageTcell11-3cytokineproducedbyTcellsIL-2IFN-gIL-4IL-5IL-10Th1+IL-2+IL-4IL-2

IFN-g抑制IL-4IL-10細胞免疫體液免疫Th0Th2Th1和Th2細胞的分化

Th1-Th2分泌細胞因子的相互調(diào)節(jié)及其效應(yīng)B細胞IgG2aTc細胞活化巨噬細胞活化B細胞IgM，IgG1，IgA，IgE肥大細胞生長嗜酸性粒細胞生長與分化B細胞，巨噬細胞Th2細胞，肥大細胞IL-12IL-4IL-10IFN-gTh1IFN-gIL-12IL-4,IL-110,IL-13IL-2IFN-gIL-2IFN-gTNF-bIL-12IL-3IL-4Th2IL-10IL-5IL-4IL-5IL-6IL-13activatedTh1cellNKcellIL-2Promotingproliferationanddifferentiationofcells,andsynthesisofIgPromotingproliferationandproductionofcytokinesActivated（LAK）ActivatedTcellBcellMacrophageNKcellInhibitionofcytotoxicity,promotingsecretionofIL-1ImmunebioactivitiesofIL-2NKIL-1g-IFNIL-4IL-5IL-6Th1Th1APCMjMj呈遞抗原抗原活化T細胞（IL-2產(chǎn)生的前體細胞）Th1Th1LAK增殖分化并分泌抗體Th1Th1B抗原刺激分化復(fù)制IL-2反應(yīng)細胞（TH或TC細胞）IL-2的生物學作用NKIL-1g-IFNIL-4IL-5IL-6Th1Th1APCMjMjAntigenpresentationantigenActivationofTcell(precursorproducingIL-2）Th1Th1LAKproliferation,differentiationSecretionofantibodyTh1Th1BantigendifferentiationreplicationIL-2reactivecells（ThorTC）ImmunebioactivitiesofIL-2TypeIinterferon：IFN-,IFN-anti-virusTypeIIinterferon:IFN-,immuneregulationinterferon,IFNCD8+Tcell,CD4+Tcell,NKcellVirus-infectedcellsImmunebiologicaleffectsofIFN-ActivatedTh1cellNKcellPromotingexpressionofMHC-IIandFc,antimicroorganismandantitumor,synthesisof

TNF-，macrophageBcellVirusinfectedcellTcellpromotingIL-2productionIL-2RexpressionEnhancingIVhypersensitivityPlantationrejectioncytotoxicityIFN-PromotingproductionofIgG3andIgG2aInhibitingexpressionofCD23andproductionofIgEPromotingActivationkilledNKcellInhibitingViralreplication,proliferation11-4Cytokineandclinicalapplicationrelateddiseases

：

deficiencyofcytokinesandreceptors

overexpressionofcytokineshighleverofsolublecytokinereceptorsTherapeuticuseofcytokinesandtheirreceptors：

supplyandadditionblockageandantagonist

CommondiseasesInfectiousdiseasestumorPlantationrejectionhematocytopeniahypersensitivityAutoimmunediseases細胞因子引起的病理反應(yīng)細胞因子病理反應(yīng)拮抗劑適應(yīng)癥IL-1發(fā)熱,炎癥,休克,低血壓,-胰島細胞毒性炎癥性疾病,休克,類風濕關(guān)節(jié)炎,糖尿病,白血病等IL-2發(fā)熱,滲漏綜合征,貧血,低血壓移植排斥,自身免疫病IL-3發(fā)熱,流感樣癥狀,刺激肥大細胞和嗜鹼性粒細胞,刺激白血病細胞

IL-4發(fā)熱,促進IgE產(chǎn)生,I型變