模式识别受体与乙肝病毒感染.ppt

DeptofInfectiousDiseasesShanghaiRuijinHospitalJiaotongUniversitySchoolofMedicineQingXiePatternRecognitionReceptorsandHBVInfectionRoleofToll-likeReceptors

HBsAgrate(%)?8: high2-7: medium2: lowHBVinfectionisstillamajorglobalhealthcareproblem350millionchroniccarriersworldwide9thleadingcausesofdeath75%ofHBVcarrierareAsianHighprevelanceWidelyspread

NatureHistoryofHBVInfectionAcuteHBVInfectionChronicHBVInfectionChronicHepatitisBCirrhosisLiverFailureHCC3-5%Adult95%Children5年6-15%5年20-23%5年12-20%AntiviraltreatmentHBVVironsCompleteResponsePartiallyResponseNonResponseImmuneasakeyfactorinfluencestheoutcomeandprogressionofdisease

Challenge:Whatmechanismofvirusclearanceofhost??Howtodothat??HBVHOSTVirusclearanceresolvedUnabletoclearvirusPersistentinfectionProgressionofdiseaseImmunefunctionofHostCentralRole

ThreeessentialelementsrequiredinliverinflammationfollowingHBVinfectionHBVVIRONSHEPATOCYTESIMMUNOCYTES

Nonantigenspecific-INNATEIMMUNITYNK/TPhagocytesNKpDCPlasmacytoidDC调节性T细胞Antigenspecific-ADAPTIVEIMMUNITYCD8CD4BTregsCD4+CD25+TregcellLINKCytokinesTypeIinterferonIL-12GranzymeBmDCMyeloidDCAntigenpresentationTh17

HostVirusClearanceHostImmuneResponseismediatedbyPatternRecognitionReceptors(PRR)whichrecognizesspecificmolecularorreplicationintermediatorofvirusparticles.HBVVironsTypeIIFNInductionActivatedCytotoxicResponse

PatternRecognitionReceptors(PRR)

RecentStudiesfound:Thecloserelationshipbetweenhostinnateimmunityandtherecognitionofpathogenandclearance.TLRasanimportantPRR,playsacentralroleindefenceofvirusinvasion.DifferentTLRcanrecognizevariouspathogen.

G+bacteriaG-bacteriaVirusVirusVirusclearance

WhatisaroleofTLRinHBVinfection??HBVG+bacteriaG-bacteriaVirusclearanceDisturbanceofTLRexpressioninducesthepersistentinfection.Abnormalofsignalpasswayinitia