醫(yī)學(xué)資料 Chapter21病毒的感染與致病機(jī)制學(xué)習(xí)課件

Chapter21

Theinfectionandpathogenicmechanismofvirus

Viralinfection

Originofviralinfection

Exogenousinfection(1)

patient(2)

carrier(3)animal(zoonoticdisease)

Thepathwayofviralinfection

1.

respiratorytract2.digestivetract3.

damagedskinormucousmembranes4.blood5.

arthropodvector6.contact:sexcontact(STD)

Themodeofviralinfectionshorizontaltransmission

Virusestransmitfromperson-to-personoranimaltoperson

verticaltransmission

Virusestransmitfrommothertooffspringthroughplacenta---fetus,congenitalinfection,

(congenitaldeformity)throughbirthcanal

---infectionofnewbornthroughbreastmilk

---fromvirus-infectedmothers

Theviruseswhichcanresultincongenitalinfection

rubellavirus

(RV)cytomegalovirus(CMV)

herpessimplexvirus-I(HSV-I)

hepatitisBvirus(HBV)

humanimmunodeficiencyvirus(HIV)

congenitaldeformity(先天性畸形)causedbyrubellaviruscongenitaldeformity(先天性畸形)causedbyHCMV

Viraldisseminationinvivo

localinfection

systemicinfection

viremia

skin/mucousmembrane

celltocellnervoussystembloodsystemThetypeofviralinfection

I.inapparentorsubclinicalinfection

virusesenterthebody,butcausenoapparentclinicalsyndrome.II.apparentinfectionorinfectiousdisease.

virusesenterthebody,whichcancauseapparentclinicalsyndrome.acuteviralinfection:virusesexistinthebodiesforashorttime(≦6month)persistentviralinfection:virusesexistinthebodiesforalongtime(＞6month)persistentviralinfection1)

chronicinfection:

viruscanbecontinuouslydetected.2)latentinfection:

virusisusuallynotdetectablebutpatientmayhaveperiodicout-breaksofdisease.SuchasHSV,VZV3)slowvirusinfection:

withlongincubationperiods(years),subacute,progressive

HIV；prion4)

delayedcomplicationafteracuteviralinfection

SubacuteSclerosingPanencephalitis(SSPE)HSVHSVThepathogenesisofviralinfectioncellvirusreceptorattachmentproteincellvirustropismI.virus–cellinteractions:

1.cytocidalinfection

viruswhichinfectandreplicatewithincellscausingthecellstolysewhentheprogenyvirionsarereleased.

CPE(cytopathiceffect)

2.steadystateinfection

virusesareproducedfromtheinfectedcellsbutthecellsarenotkilledbytheprocess.---cellfusionsuchasHCMV---integrationofviralAgincellmembranes

suchas

influenzavirus,HBV

cytopathiceffect(CPE):--Thepresenceofthevirusoftengivesrisetomorphologicalchangesinthehostcell.Anydetectablemorphologicalchangesinthehostcellduetoviralinfectionareknownasacytopathiceffect.--Cytopathiceffects(CPE)mayconsistofcellrounding,disorientation,swellingorshrinking,death,detachmentfromthesurface,etc.

3.inclusionbodyround,oval,orirregular-shapedbodiesoccurringinthecytoplasmornucleusofvirus-infectedcells,whichcanbeseenunderthemicroscope.

4.cellapoptosisvirusorviralprotein(e.g.HIV)5.viralgenomeintegration

integration:

integrationoftheviralgenomeintocellularDNA.(e.g.HIV)

cellproliferationandtransformation

morphologicalchange

immortalization

e.g.

oncogenicvirus

oncogenicvirusHBV---hepatocellularcarcinoma

HCV---

hepatocellularcarcinoma

HPV---cervicalcarcinomaEBV---Burkittlymphoma,nasopharyngealcarcinoma

HHV8---KaposiSarcoma

HTLV---TcellleukemiaII.virus–immunesysteminteraction:

immunopathologicalreactions---Hypersensitivity:

typeIIresponse(cytotoxic)typeIIIresponse(immunecomplex)typeIVresponse(cell-mediatedordelayed)

theinjuryofimmunesysteminducedbyvirusinfection:

immunosuppressive

Virusinfectimmunocyte

killtheimmunocyte

auto-immunitycanbeinducedbyviralinfections

ImmunityagainstviralinfectionsSectionIII

Non-specificimmunity

Specificimmunity

Non-specificorinnateimmunityanatomicalbarriers

humoralfactors

phagocyticcellsNKcellsAcquiredimmunity

humoralimmunity

cell-mediatedimmunity

IgEIgGIgDIgMIgAperforingranzymeIFN-

IL-2、TNF-

MucosaimmunityCD+4Th1CD+

8CTLSIgA

1.skinandmucosa

barrier：

①

theintactskinandmucousmembranesofthebodyaffordahighdegreeofprotectionagainstpathogens.②

secretebactericin,fattyacid,lacticacid，

lysozyme，lactoferrinetc.③

normalflora2.hemo-spinalfluidbarrier3.placentalbarrier

Anatomicalbarriersnaturalkillercell

NKcell：

Recognizechangeonvirus-infectedcellsanddestroythembyanextracellularkillingmechanism.Roleinearlyviralinfectionorcarcinogenesisbeforeactivationofacquiredimmunity.

inherentbarriers

Skin,Mucus,Ciliatedepithelium

,LowpH

NKcell

humoralandcellularcomponents

interferon(IFN)

complement

cytokines:TNF-α,IL-1andIL-6…

Non-specificimmunityInterferon（

IFN）concept:

Aclassofprotein(glycoprotein)producedbycellsinresponsetoviralinfectionorotherinterferoninducersthatprotectedothercellsofsamespeciesfromattackbyawiderangeofviruses.

productionofIFN:

interferoninducers:PolyI:Cvirusbacterialendotoxin,etc

productionofIFN:IFNinduceractsoncellreceptorsIFNgeneactivationIFNmRNAtranscribeIFNsynthesisIFNreleasedCharacteristics:

1）notactdirectlyonvirus

2)broad-spectrumantiviralactivity3)hostspeciesspecific:

inhibitviralreplicationonlyinthespeciesinwhichitwasproduced4)Immuno

opsonizationandanti-tumor

classificationofIFNs:HuIFN;MuIFN……

IFN-α

IFN-β

IFN-γGenechromosome9

chromosome9

chromosome12cellbloodmononuclearcell

fibroblasts

Ag-activatedTcellanti-viral+++

+++

++ActivityModify-immune++

++

+++responsesantiviralactivity:

cannotactdirectlyonvirus,butthroughinductionofantiviralproteins(AVP).

IFN抗病毒作用示意圖

Mechanisms:

IFNcombinescellsurfaceAVPgeneactivationAVPmRNAtranscribeAVPsynthesis.

AVPconsistsof:proteinkinaseR2,5-Asynthetase

Specificimmunity

humoralimmunity

neutralizationantibody

cellmediatedimmunity

CD+8CTLCD+4Th1

1.neutralization

antibody

bindtoenvelopeorcapsidproteinofvirus,blockingthevirusreplication

adsorption

bytheinhibitionof

penetration

IgGIgMIgAmechanism:

(1)virolysis---bycomplement