細(xì)胞因子及其受體

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

Cytokine由免疫細(xì)胞和某些非免疫細(xì)胞（如血管內(nèi)皮細(xì)胞、表皮細(xì)胞和成纖維細(xì)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(xì)胞因子(cytokine)CytokinegeneInducingstimulusCytokine-producingcellCytokineGeneactivationReceptorsignalBiologicaleffectsOverviewoftheinductionandfunctionofCytokine生物學(xué)效應(yīng)：免疫細(xì)胞之間的信息交換及相互調(diào)節(jié)依賴于細(xì)胞因子。細(xì)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(guò)程之外，還對(duì)傷口愈合、造血干細(xì)胞再生與分化密切相關(guān)。-S-S--S-S--S-S-CC

CCC1C3C2C1C3C2C1C3C2C1C3C2G蛋白細(xì)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(xì)胞因子的主要生物學(xué)效應(yīng)抗感染和抗腫瘤作用免疫調(diào)節(jié)作用參與細(xì)胞凋亡刺激造血細(xì)胞增埴分化促進(jìn)各種細(xì)胞的生長(zhǎng)和分化參與和調(diào)節(jié)炎癥反應(yīng)細(xì)胞異常可導(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(shí)別（感應(yīng)）階段

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

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

細(xì)胞因子對(duì)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(jìn)而促進(jìn)腎上腺皮質(zhì)激素的釋放 應(yīng)激時(shí)兒茶酚氨和糖皮質(zhì)類固醇分泌增多，進(jìn)而抑制IL-1、TNF的合成。 在免疫應(yīng)答過(guò)程中，免疫細(xì)胞之間通過(guò)細(xì)胞因子相互刺激、彼此約束，對(duì)免疫應(yīng)答進(jìn)行調(diào)節(jié)，維持免疫系統(tǒng)的穩(wěn)態(tài)平衡。1.白細(xì)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(zhǎng)因子(growthfactor,GF)細(xì)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(xì)胞集落刺激活性的細(xì)胞因子

主要產(chǎn)生細(xì)胞作

用SCF纖維母細(xì)胞，肝細(xì)胞，內(nèi)皮細(xì)胞，上皮細(xì)胞，基質(zhì)細(xì)胞所有類型的造血干細(xì)胞，黑色素細(xì)胞，肥大細(xì)胞IL-3T細(xì)胞中性粒細(xì)胞，單核細(xì)胞，紅細(xì)胞，嗜堿性粒細(xì)胞IL-5T細(xì)胞嗜酸性粒細(xì)胞IL-11基質(zhì)細(xì)胞，纖維母細(xì)胞所有類型的造血干細(xì)胞，血小板GM-CSFT細(xì)胞，單核細(xì)胞，內(nèi)皮細(xì)胞，纖維母細(xì)胞中性粒細(xì)胞，單核細(xì)胞，嗜酸性粒細(xì)胞，樹突細(xì)胞G-CSF單核細(xì)胞，纖維母細(xì)胞，中性粒細(xì)胞M-CSF單核細(xì)胞，淋巴細(xì)胞，纖維母細(xì)胞，內(nèi)皮細(xì)胞，上皮細(xì)胞單核細(xì)胞，胎盤滋養(yǎng)細(xì)胞EPO腎臟細(xì)胞紅細(xì)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(xì)胞胸腺細(xì)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(xì)胞IL-4IFN-5.拮抗性antagonism3.重疊性redundancy4.協(xié)同性synergy均有刺激B細(xì)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(xì)胞因子受體免疫球蛋白超家族（IgsF）造血細(xì)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(xì)胞免疫體液免疫Th0Th2Th1和Th2細(xì)胞的分化

Th1-Th2分泌細(xì)胞因子的相互調(diào)節(jié)及其效應(yīng)B細(xì)胞IgG2aTc細(xì)胞活化巨噬細(xì)胞活化B細(xì)胞IgM，IgG1，IgA，IgE肥大細(xì)胞生長(zhǎng)嗜酸性粒細(xì)胞生長(zhǎng)與分化B細(xì)胞，巨噬細(xì)胞Th2細(xì)胞，肥大細(xì)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(xì)胞（IL-2產(chǎn)生的前體細(xì)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(xì)胞（TH或TC細(xì)胞）IL-2的生物學(xué)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(xì)胞因子引起的病理反應(yīng)細(xì)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(xì)胞毒性炎癥性疾病,休克,類風(fēng)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(xì)胞和嗜鹼性粒細(xì)胞,刺激白血病細(xì)胞

IL-4發(fā)熱,促進(jìn)IgE產(chǎn)生,I型變