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更改實驗課更改實驗課地點通原207室實驗課,改在409實驗室上請各位同學按改動后的地點前往上課并互相提醒1MedicalInfectionandMedicalInfectionandPathogenesisof——ForthecourseofMedicalMicrobiology,the8-yrmedicalprogram,Class2020,SYSUDecember7-14,MengfengLi黎孟楓DepartmentofMicrobiology,ZhongshanSchoolMedicine,SYSU,Guangzhou,2HerpesKaposiHerpesKaposi3WhatdoesapathogenhaveWhatdoesapathogenhaveto(foritsown?Enteringahosttoreproduce(replicate)itself(foravirus,intracellularly!)?TransmitprogenytoanotherhosttoproducemoreButwhatifitdoesn’t——disappearingfromorsilencedinthe4MechanismsofWherearetheywhenMechanismsofWherearetheywhentheyarebetweenhosts(e.g.,?Aerosols-inhalationofdroplets,e.g.Rhinoviruses,the'CommonColdVirus'orAdenoviruses.?Fecal-Oral-e.g.,Astroviruses,Caliciviruses,Polioviruse,EV71,HAV.Someofthesevirusescauseacute?Vector-borne-e.g.viaArthropodssuchasmosquitos,ticks,fleas:Arboviruses.?Closepersonalcontact-especiallyexchangeofbodilyfluids:Sex;Blood,e.g.Herpesviruses,HIV,EV71(?)5EntryintoEntryintotheDifferentvirusesusevariousentrysitestoinfectthehost6EntryintotheEntryintotheCommonentrysitesusuallypossesslocaldefense/immunefunction–inappropriatechemicalssuchasgastricacidandbileciliated7EntryEntrySkin–Cuts/wounds,abrasions;orthroughtransmissionvectors,e.g.,ticks,mosquitoesorvampirebatstobreachtheskinbarrier.Respiratorytract–Viruseshavetoovercomethemucosaimmunedefensemechanisms(sIgA,mucussecretion,lowtemperature,cilliatedepithelium).–Droplets,sputum,saliva,8?Gastrointestinaltract-a?Gastrointestinaltract-ahostileenvironment;gastricacid,bilesalts,etc–Feces,contaminated?Urogenitaltract-relativelylesshostilethanGItract,butlessfrequentlyexposedtoextraneousviruses(True?)–Sex,labordelivery,inuterus(mother-to-?Conjunctiva-anexposedsiteandrelatively–Direct/indirectcontact,swimming9Patternsof?HorizontalTransmission:directPatternsof?HorizontalTransmission:directperson-to-person?VerticalTransmission:fromparentstoFormsofverticalNeonatalinfectionatbirth,e.g.hepatitis,AIDS.Infectioninuterus,e.g.,CMV,Rubella,AIDS.Germlineinfection-viaovumorsperm.LocalizedvsSystemicLocalizedvsSystemicHavinggainedentrytoapotentialhost,virusmustinitiateaninfectionbyenteringasusceptiblecell→PrimaryreplicationThisusuallydetermineswhetherinfectionwillremainlocalizedatthesiteofentryorspreadtobecomeasystemicCertainvirusCertainvirustypesareabletospreadfromtheentrysitethroughoutthehost,causingsystemicinfection,via:thethenervousviathePrimaryinfectionDirectinoculationviathePrimaryinfectionDirectinoculation(Arthropodvectors,bloodtransfusion,orI.V.drugabuse)Inthebloodstream,virusesmay(Primarytravelfreeintheplasma:Togaviruses,ORassociateRBC:platelets:lymphocytes:EBV,monocytes:Primaryfollowingprimaryreplication,Primaryfollowingprimaryreplication,whichoccursatentryrelativelylowvirusSecondaryfollowingsecondaryreplication(e.g.,spleen,lymphoidhigherreachesothertargettissuesordirectlyinbloodcells→systemicSecondaryOccursinSecondaryOccursinsystemicinfectionswhenavirusreachesothertissuesthantheentrysitesinwhichitiscapableofreplication,e.g.Poliovirus(gutepithelium→neuronsinbrain&spinalcord)orLentiviruses(macrophages→CNS+manyothertissues).Ifaviruscanbepreventedfromreachingtissueswheresecondaryreplicationcanoccur,generallynoclinicaldiseaseoccursinthistissue.viatheviathenervousPrimaryviremiaORdirectcontactwithneuron→nervoussystem(peripheralnerves→CNS)SummaryofsystemicEntry→PrimarySummaryofsystemicEntry→Primaryreplication→Localized/SuperficialPrimaryPeripheralSecondarySecondaryCNSSystemicExamplesoflocalizedvssystemicLocalizedSystemicPrimaryExamplesoflocalizedvssystemicLocalizedSystemicPrimarySecondaryEnterovirus(e.g.,IntestinalLymphoidtissues,OropharynxorG.U.Lymphoidcells,PrimaryIntestinalCell/TissueTropism-theabilityofaCell/TissueTropism-theabilityofavirustoreplicateinaspecifictypeofcellsortissues??Controlledpartlybytherouteof?Butmoreimportantly,bytheinteractionofavirusattachmentprotein(VAP)withaspecificreceptormoleculeonthesurfaceofacell(ManyVAPsandvirusreceptorsare?Alsoattributedtotissue/cellspecificityofviral?Otherfactors:e.g.,presence/absenceofkeyenzymes(HP-?ConsiderablyimpactonClinicalFormsofClinicalFormsofInapparentinfection(SubclinicalApparentAcutePersistentChronicLatentSlowvirusInapparentinfection(Subclinicalinfection)Noclinical??Inapparentinfection(Subclinicalinfection)Noclinical??Maybeattributabletoinsufficientpropagationofthevirusdueto:–––certainvirustypesweakvirulence,and/orhostimmunity?Maystillbereplicableandreleasedfromthehost→carrierofvirusApparentAcuteApparentAcuteviralshortincubationperiod(hours–shortclinicalcourse(days–protectivetypicalexamples:commoncold,flu,hepatitisALongLongtermpersistenceofvirusresultsfromtwomainmechanisms:SuppressionofthelyticEvasionofimmunePersistentViralPersistentViralLonglastingpresenceofvirusintheSuppressionofthelyticEvasionofimmuneMaybeattributedcompromisedhostimmuneviruslocalizedtohiddenweakviral-viralCommonformsofpersistentChronicLatentSlowvirusChronicVirusChronicViruscontinuouslydetectableMildornoclinicalsymptoms??LatentVirusLatentViruspersistinginanoccult(orcryptic)formmostofthetimeIntermittentflare-upsofclinicaldiseaseInfectiousvirusrecoverableduringflare-upsTypicallypersistfortheentirelifeofthe????SlowvirusSlowvirusAprolongedincubationperiod(months–years)Viruscontinuously,butveryslowly,multipliesTypicallynoclinicalsymptomsevidencedduringthelongincubationperioduntilthedisease???HOWdoesaviruscauseHOWdoesaviruscauseaInterferingwiththefunction/survivalofthehostcells——DirectpathogenicImmunopathogenesis——IndirectpathogeniceffectsFacilitatingorcomplicatinginfectionsofothermicrobes(e.g.,bacteria)CellularmechanismsCellularmechanismsofviral——DirectpathogeniceffectsonhostCellularoutcomesofviral1.Cellularoutcomesofviral1.Cytolyticinfection(cytolysis,cytocidal–numberofviralparticles→releasedtoinfectothercellsCytopathiceffect(CPE)whenculturedin–Mostlycausingacuteinfection,withafewexceptionsofchronicinfection(whenonlyafewcellsareinfectedwhiletherestproliferate)–Pathogenic????InhibitionofcellularbiosynthesisIncreasedpermeabilityoflysosomesToxicviralcomponentsOtherdirectdamagestosubcellular2.Steadystate2.SteadystateThehostcellliveswhenthereplicatingcausesonlymildcellularchanges;releasesthroughbudding(ratherthancytolysis,frequentlyenvelopedviruses)orinter-cellularmembranefusion.Mayproducenewviralparticles(productive)ornot(nonproductive),oralternatelybothLatency??→3.??oneformof3.??oneformofcellsuicide(programmedcellmorphologicallycharacterized(wrinkledmembraneandcondensednucleus)mediatedbyacascadeofmolecularreactions,eventuallyleadingtocellularDNAdegradationtriggeredbyavarietyof“deathsignals”,includinginfectionorreplicationofsomeviruses??4.Integrationofviralgenomeinhost?canberelevanttopersistentinfectionand/orcell5.Transformationof5.TransformationofthehosthostcellssubjectedtoincreasedDNAsynthesisandmultiplicationratherthanbeingkilledorinhibitedbythevirusaccompaniedbymorphologicalchangesrelevanttoimmortalizationorevenmalignancy(cancer)maybeproductive(RNAtransformingviruses)orproductive(DNAtransformingExamples:EBV,HPV,HTLV,Summary:TypesofviralinfectionsatthecellularSummary:TypesofviralinfectionsatthecellularVirusFateof-+No+-LittleDNARNA-+Imortalaion/man3ncyImmunopathogenesisofviraldiseasesImmunopathogenesisofviraldiseases——IndirectpathogeniceffectsofvirusViralVariousViralVariousScenariosofvirus-immunesysteminteraction—ThreeViralpathogenesismediatedbytheimmuneViralpathogenesismediatedbytheimmuneDeregulatedproductionofcytokines:TNF-,MIP,IP-10,IL-8,etc.HypersensitivitytypesII,IIIor①②③④HostcellmembraneAgalteredbyvirusCrossreactionbetweenviralandhostAgInhibitionofsuppressorTcellsErroneousrecognitionbylymphocytesduringviral?SARS?Bird’sflu?FulminanthepatitisViralpathogenesisactingagainstViralpathogenesisactingagainstimmuneImmunesystemasthetargetofavirus:e.g.,HIV––Non-specificimmunosuppressionbyviralinfection:e.g.,CMVinfection,Measlesvirus–Damagetolocalbarrier→facilitatingcomplicatinginfectionsofothermicrobes:SARS-CoVandchlamydia/bacterialinfection!Viralinfection/pathogenesisenhancedViralinfection/pathogenesisenhancedtheimmune–Antibody-dependentenhancementofviralinfection——ADEeffectExamples:DenguefevervsDenguehemorrhagicfever;Epidemichemorrhagicfever(renalsyndrome)–?–Aerosols,Fecal-Oral,Vector-borne,Closepersonal?Sitesofvirus–Skin,Respiratorytract,GI?–Aerosols,Fecal-Oral,Vector-borne,Closepersonal?Sitesofvirus–Skin,Respiratorytract,GItract,Genitourinarytract,?Transmission–HorizontalvsVertical???LocalizedvsSystemicViralInfectionPrimaryvsSecondaryviremiaClinicalFormsofInfection(Typesofviralinfectionsattheclinical––Apparentinfection:??Acuteinfection–––ChronicinfectionsLatentInfection?Typesofviralinfectionsatthecellular–––AbortiveinfectionCytolyticinfection?Directpathogeniceffects——cellulareffectsofviral––––CytolyticeffectsandApoptosisFormationofinclusionbodiesIntegrationofviralgenomeinhostchromosomeTransformationofthehostcells?Immunopathogenesis——Indirectpathogenic–––ViralpathogenesismediatedbytheimmunesystemViralpathogenesisactingagainsttheimmunesystemViralinfection/pathogenes

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