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ImmunoregulationGuangjieChenDept.ofImmunologyandMicrobiology2014ImmunoregulationGuangjieChenImmunefunctions:ImmunedefenseImmunehomeostasis----immunologicaltoleranceandimmunoregulationImmunesurveillance
Immunefunctions:Immunoregulation:positiveandnegativedirectionLevels:molecularlevel,cellularlevel,holisticlevelandpopulationlevelImmunoregulation:positiveaI.ImmunoregulationistheabilityofimmunesystemitselfSenseandimmunoregulationI.ImmunoregulationistheabantigenTiterofAbDaysafterimmunizationtestcontrolExchangeserumfromanotherrabbitwithoutimmunizationantigenTiterofAbDaysafteri2.Responseandimmunoregulation
negative
feedbackregulationisthemainstream3.Immunoregulation
andintervention4.Immunoregulation
and
diseases:SARS2.ResponseandimmunoregulatiII.Immunoregulationininnateimmuneresponse1.ImmunologicalregulationinTLRmediatedresponse
TLR—PAMP:NF-kB,MAPKpathway---inflammatorygeneactivated,inflammatoryresponseeliminatepathogensII.Immunoregulationininnate《雨铃铛》PPT【精美版】timeofinflammatoryresponseEarlyLaterIntensityofresponseStageofeffectMaintainsuitableintensityStageoftoleranceNoreactivityinhibitorysignalinhibitorysignal
stimulatingsignal
timeofinflammatoryresponseE2.SOCS(suppressorofcytokinesignaling)
CK-CKR------signaltransduction----targetgeneactivated
SOCS
geneactivated,inducenegativefeedback2.SOCS(suppressorofcytokin《雨铃铛》PPT【精美版】3.Regulatoryproteinofcomplement
C1INH:inhibitclassicalpathway
CD55(DAF),CR1:inhibitingformationofCconvertase
CD59:inhibitingformationofMAC3.RegulatoryproteinofcomplIII.Inhibitoryreceptormediatedimmunoregulation1.Immunoregulationbytransductionsignal
(1)PTK,PTPPTK
PTP
III.Inhibitoryreceptormedi(2)ITAMandITIMITAMCD3、Ig
、Ig
、FcRIITIM
CTLA-4、FcRIIB、KIR(2)ITAMandITIMITAM:twoYxxL/Vconservedsequence:Y--tyrosine,L—leucine,V—valineY-phosphorylation,binewithcytoplasmicPTK(ZAP-70),transductionTCRacceptableantigenstimulationsignalITAM:ITIM:I/VxYxxL:I—isoleucine
Y—phosphorylation,bindtoSHP-1andSHIP,inhibitthetransductionsignalofTcellactivationITIM:ActivationsignalsInhibitorysignalsActivationsignalsInhibitory2.Immunoregulationbyinhibitoryreceptors
(1)co-stimulatorymoleculesCD28-----B7:activationCTLA-4-----B7:inhibition(after24h)PD-1-------PD-L1/2:inhibition*Noactivationthereisnoinhibition2.Immunoregulationbyinhibitactivationinhibitionactivationinhibition《雨铃铛》PPT【精美版】(2)FcRIIb(Bcells)
(2)FcRIIb(Bcells)(3)InhibitoryreceptorsofNKcellInhibitoryreceptorsandtheirligandsactivatingreceptorsandtheirligands(3)InhibitoryreceptorsofNKIV.ImmunoregulationbyregulatoryTcellcharacteristicsnTregiTregInductionsitethymuspheripheralCD25
expression+++-/+Foxp3++++Ag-specificAuto-antigen(thymus)Tissue-specificantigenandforeignantigeneffectCell-cellcontact,cytokineproductionCytokinedependentfunctionInhibitionofauto-reactiveTcellimmuneresponseInhibitionofauto-reactiveinflammationandgraftrejection,benefitforcancerIV.Immunoregulationbyregul《雨铃铛》PPT【精美版】iTreg:Th3:TGF-
Tr1:IL-10iTreg:《雨铃铛》PPT【精美版】《雨铃铛》PPT【精美版】V.Regulationbyidiotypeandanti-idiotypenetworkAb(Id)——AIdV.RegulationbyidiotypeandImmunogenicityofimmunoglublinImmunogenicityofimmunoglublsuppressAb1:treatmentofautoimmunediseasesAntigenicinternalimageenhanceAb1:treatmentofAIDSandtumorIdiotypeandanti-idiotypenetworksuppressAb1:treatmentofaut《雨铃铛》PPT【精美版】《雨铃铛》PPT【精美版】TcellsTcelllinesExpansionTcelllinesIrradiation1stinjection2ndinjection3rdinjection1months1monthTcellsTcelllinesExpansionTIdiotypiccellAnti-idiotypiccellinducecytotoxcity
IdiotypenetworksIdiotypiccellAnti-idiotypiccIdiotypenetworksinducedbyTcellvaccineMonths
CD8+granzyme-BsecretingTcells******Positivecells/106purifiedTcellsIdiotypiccellAnti-idiotypiccellinducecytotoxcity
IdiotypenetworksinducedbyTVI.ImmunoregulationbyAICDActivationinducedcelldeathFasL-Fas(apoptosis)VI.ImmunoregulationbyAICDA《雨铃铛》PPT【精美版】《雨铃铛》PPT【精美版】AutoantigensAutoantigeninducedTcellexpansionAutoimmunelymphoproliferativesyndrome,ALPSAutoantigensAutoantigeninduceVI.EffectsoftheneuroendocrinesystemonimmunesystemVI.Effectsoftheneuroendocr《雨铃铛》PPT【精美版】《雨铃铛》PPT
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