大二下學習微生物課件21 hbv new

Chapter25

HepatitisVirus

p.329學習要求重點掌握1.甲～戊五種肝炎病毒的生物學性狀：基因組特征、抗原組成、抵抗力2.五種肝炎病毒的致病性與免疫性：傳播途徑、致病特點、致病與免疫機制3.五種肝炎病毒的微生物學檢查法及預防措施

難點1.乙型肝炎病毒的基因結(jié)構(gòu)與功能2.乙型肝炎病毒的致病與免疫機制3.五種肝炎病毒血清標記物檢查及其臨床意義病毒性肝炎的流行特點世界性傳染病傳染性強傳播途徑復雜流行廣泛發(fā)病率較高4病毒性肝炎的臨床特征乏力食欲減退惡心、嘔吐肝腫大肝功能損害黃疸Ingeneral,hepatitisvirusesresultin:

acuteinflammationofliver;

clinicalfindings:fever,gastrointestinalsymptom,jaundicecomposedof:

HAV,HBV,HCV,HDV,HEVandHGV,TTVdependingon:

genome,pathogenicty,clinicfindings,etc.HepatitisAvirus(HAV)

belongedtoenterovirus,type72DistributionofHAV

mainlyindevelopingcountriesI.Biologicalproperties1.Morphology:27~32nm,sphericalparticle,+ssRNAvirus,7.5kb.

oneserotypeintheworld,but7genetypesinChina,IAsubtypeismostcommonMorphologyofHAV

EM;Feinstone（1973）Solid

particleswithinfectivityempty

particleswithoutinfectivityStructureofHAV2.Genestructure:3.Cultivation:animals---monkeytissuecultures---Vero,FRhk64.Resistance:

stableunder56℃,acidandbasic,ether;destroyedby100℃5min,andformalinII.Pathogenicityandimmunity

1.Source:acutepatientstransimssion:fecal---oral(mainly)2.Pathogenesis:virusoralintestinallymphnodeviremialiverdirectdamageandimmunopathogenesis(highlevel

-IFNpromoteHLAexpressionandCTLactivity)3.Immunity:persistentimmunityafterrecovery,

IgMandIgGTransmissionpathwayIII.Laboratorydiagnosis

1.Antibody:IgM(important),IgG2.HAVparticlesorantigen3.HAVRNA---RT-PCRIV.Preventionandtreatment

1.prevention:inactivatedandattenuatedvaccinespassiveimmunization2.treatment:supportiveHepatitisBvirus(HBV)

HBVbelongstoHepadnaviridae

---1963,Blumberg(Australian)—HBsAg---1970,Dane(England)----HBVviralparticle---1979,genomesequencing---atpresent,0.35billioncarriersintheworld,0.12billioninChina

mostharmfultohealthy:hepatitiscirrhosis(15%-40%)hepatocellularcarcinomaDistributionofHBV

I.Biologicalproperties1.Biologicalproperties

threemorphologicparticles1)Daneparticle:42nmwithdoublecoats,dsDNA,3200bp,infectiousformofHBV.(envelope=7nm,virioncore=27nm)2)Smallsphericalparticle:22nmwithHBsAgonly.3)Tubularorfilamentousform:22nmwidthwith50-500nminlength.Daneparticle

42nm,doubleshells,containallofantigens:HBsAg,PreS1,PreS2,HBcAg,HBeAg)andcore(DNA,DNApolymerase),withinfectivitySphericalparticlePipe-likeparticle---22nm,containingHBsAg---22nm,long50-500nm---withoutPre-S1andPre-S2PTA:phosphotungsticacid2.Compositionofviralantigens1)HBsAg:glyco-lipoproteininviralsurface.124-147aa“a”epitope,adrvsayw2)Pre-SAg:pre-S1,pre-S2.3)HBcAg:protein,viralcoreAg.innernucleocapsid(difficultforchecking)4)HBeAg:protein,viral

eAg.secretedintoserum

PreSAntigens:

PreS1:119(128)aa.TopromoteImmunogenicityofHBsAg

PreS2：55aa.PossessPHSA-ror

硫酸肝素蛋白聚糖？attachonlivercellsurfacebywayofPHSAbridge.

AntiPreS2：blockingthePHSA-rorreceptor.3.GenomeStructureHBVgenomePartialdsDNAProm:promoterEnh:enhancerGRE:glucocorticoid

responsiveelement4.VirusReplication5.VirusVariation

PreS/S:mutationincodede145or126aaof“a”epitopePreC/C:PreC---1896GA(TAG)C---1762-1764Typing:sero-typing:8typesgene-typing:main4ytpesII.PathogenisityandImmunity1.TransmissionSources:Patients,HBVcarriers.Routes:bloodorbloodproducts,parentaltransmissionsexualtransmissionintimatecontact……2.pathogenicmechanisms(1)hypersensitivitytypeⅣ:a.CTLtoHBcAg:perforin+FasLb.Th:IFN-γ,IL-1,TNF-α---inflammation,necrosis(2)Immuno-pathologymediatedbyAb:plex---hypersensitivitytypeⅢviralAg(HBsAg,HBeAg)(3)autoimmunity:againstLSPandLMAg,viaADCCandCTLSummary:Intra-liver:CTLThautoimmunityExtra-liver:

hypersensitivitytypeⅢ3.Relationshiptohepatitisandimmunityliverpathologicalchangesisdependonimmuneresponse!ImmunityagainstHBVnormal:acutehepatitis(CTL+Ab)strong:serioushepatitis(CTL+Ⅲallergy)lower:chronichepatitistolerance:carrier4.Relationshiptocirrhosisandhepatocellularcarcinoma1).Cirrhosis(15%-40%)2).hepatocellularcarcinoma(HCC)HBVisariskfactorinthedevelopmentoflivercancera.infectionVSno-infection,higher217timesb.trans-activationbyHBx(transactivator)c.HCCintegratedHBVDNAd.HCCmodelofwoodchunksinfectedwithhepatitisvirusNormalliverviralhepatitis

NormallivercirrhosisIII.Microbiologicdiagnosis:1)SpecificAg&Ab:ELISA(EnzymeLinkedImmunosorbentAssay)RIA(RadioImmunoassay)Immunodiffusion(forSubtype)Westernblot(peptidefragments)2)HBVDNA:DNAhybridizationtechniquesPCR(Polymerasechainreaction).3)DaneParticle:IEM4)DNApolymerase:eventheliverpuncturespecimenWindowtimeGeneralPatternofHBVinfectionPatternofchronicdiseaseALTandHBsAgareimportantindicatorsforHBVinfectionIV.Preventionandtreatment1.generalmeasures:Isolationofpatient’swithacutehepatitis;Screentheblooddonors;Sterilizationofmedicalinstruments……2.Immunization:1)ActiveImmunization:Vaccinesincluding(1)fromplasmaofHBsAgasymptomaticcarriers;(2)fromGeneticEngineering:CHO;yeast;PoxVaccine.(3)synthesizedpolypeptideandDNAvaccineProcedure:a.Usuallyfornewborninfants:“O-1m-6m”；

b.newborninfantsofHBsAg+，HBeAg+mother:HBIg0,

after1-2weeks,vaccination

2)PassiveImunization:HBIg:injection(i.m)(1)mother’sHBVindicatorspositiveHBeAg:<6h;HBsAg<24h(2)Occupationalaccidents(3)misusedproductswithHBsAgpositive3.treatmentofpatients:supporting:rest,appropriatenutrition.Medicine:IFN-α,

adefovir(阿德福韋),3TC(Glaxoe,UK),Chineseherbmedicine.Review:1.Pleasedescribethebasicstructureof

Daneparticle?2.HowtointerpretthesignificancesofHBVantigensandtheirantibodies?3.HowtopreventthetransmissionofhepatitisBvirus?

HCVandHEV HCVHEV Size 60nmdiameter 30-35nmdiameter Envelope yesno,withspikes Core 9.5kb,+ssRNA 7.5kb,+ssRNA Transmission blood,verticalfecal-oral Clinic similartoHBV similartoHAV Immunity unknownyes復習思考題試比較HA