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Chapter6
Bacterialinfectionandimmunity
細(xì)菌的感染與免疫第一頁,共69頁。BasictermsBacterialinfection〔細(xì)菌的感染〕Pathogen〔病原菌〕Nonpathogen〔非病原菌〕Opportunisticpathogen〔時機致病菌〕第二頁,共69頁。BacterialInfection細(xì)菌的感染Theprocessofbacteriainvadinginthebody,growinginthetissues,producingtoxinsandcausingdiseasesiscalledbacterialinfection.第三頁,共69頁。Pathogen〔病原菌〕Pathogenicbacterium〔致病菌〕Abacteriumwhichcancauseadiseaseiscalledpathogen.Nonpathogen〔非病原菌〕Nonpathogenicbacterium〔非致病菌〕Abacteriumthatdoesnotcausediseaseiscallednonpathogen.第四頁,共69頁。Opportunisticpathogen〔時機致病菌〕Conditionedpathogen〔條件致病菌〕Somebacteriaarecapableofcausingdiseasesonlyundercertainconditions.Theseorganismscancausediseaseonlyifoneormoreoftheusualdefencemechanismshumanshaveevolvedtorestrictmicroorganismsfromtheirusuallysterileinternalorgansandtissuearebreachedbyaccident,byintent(e.g.surgery),orbyanunderlyingmetabolicoraninfectiousdisorder(e.g.AIDS).第五頁,共69頁。OutlineNormalfloraandopportunisticpathogenBacterialpathogenesisThehostimmunedefencesystemTheinitiationandcourseofinfectionHospitalinfection第六頁,共69頁。Section1
Normalfloraandopportunisticpathogen
正常菌群與時機致病菌第七頁,共69頁?!颪ormalflora〔正常菌群〕Normalmicrobialflora〔正常微生物群〕Thepopulationofmicroorganismsthatinhabittheskinandmucousmembranesofhealthypersons.Theyareusuallyharmless,someevenbeneficial,tohuman’shealth.第八頁,共69頁。LocationsSurfacetissuesofskinOralcavityRespiratorytractGastrointestinaltractGenitourinarytract第九頁,共69頁。Normalfloraonintestinalmucosa第十頁,共69頁。腸道的正常菌群第十一頁,共69頁。第十二頁,共69頁?!顱eneficialeffectsofthenormalfloraBiologicalantagonism〔生物拮抗〕Productionofessentialnutrients〔營養(yǎng)作用〕Primingofimmunesystem〔免疫作用〕Anti-aging〔抗衰老作用〕第十三頁,共69頁。Biologicalantagonism(生物拮抗)Biologicalbarriers〔生物屏障〕orReceptorcompetition〔受體競爭)Harmfulmetabolites〔有害代謝產(chǎn)物〕Nutrientcompetition〔營養(yǎng)競爭〕第十四頁,共69頁。Conditionedpathogen〔條件致病菌〕Somebacteriaarecapableofcausingdiseasesonlyundercertainconditions.Thesebacteriaarecalledopportunistic(conditioned)pathogensandthiskindofinfectioniscalledopportunisticinfection〔時機性感染〕.★Opportunisticpathogen〔時機致病菌〕第十五頁,共69頁?!?/p>
ConditionsofopportunisticinfectionChangeofinhabitingplaces〔寄居部位改變〕Immunesystemcompromise〔宿主免疫功能低下〕Dysbacteriosis〔菌群失調(diào)〕第十六頁,共69頁。Dysbacteriosis〔菌群失調(diào)〕Iffloradisequilibriumoccurs,forexample,whentheresidentfloraisdisturbed,somelittlesignificantmicroorganismsmaycolonize,proliferate,andproducedisease,whichiscalleddysbacteriosis.Dysbacteriosismainlyresultedfromlongtermandlargedosesantibioticstaken.第十七頁,共69頁。Superinfection〔重疊感染〕Afrequentcomplicationofdrugtherapyformicrobialinfection.Itmayresultfromopportunisticcolonizationfollowingimmunosuppressionbytheprimarypathogenandcanbeinfluencedbythetimeintervalbetweeninfections,microbialphysiology,orhostresistance.第十八頁,共69頁。Dysbacteriosisandsuperinfection第十九頁,共69頁。腸道的正常菌群安康青壯年糞便涂片安康老年糞便涂片〔雙歧桿菌〕第二十頁,共69頁。Probiotics〔益生菌〕第二十一頁,共69頁。Probiotics〔益生菌〕&Prebiotics〔益生元〕第二十二頁,共69頁。Section2
BacterialPathogenesis
細(xì)菌的致病作用BasictermsBacterialPathogenicity
BacterialvirulenceNumberofinvadingorganismsPortalofentry第二十三頁,共69頁。Pathogenicity〔致病性〕isusedtodescribethecapacityofbacteriatoinitiatediseases.Thetermofvirulence〔毒力〕isusedasacomparisonofpathogenicityinthequantitativesense.ID50〔medianinfectiousdose,半數(shù)感染量〕:Infectiousdoseofbacteriafor50%ofthetestpopulation.LD50〔medianlethaldose,半數(shù)致死量〕:Lethaldoseofbacteriafor50%ofthetestpopulation.BasicTerms第二十四頁,共69頁。ExotoxinPili(Fimbrial)CapsuleVirulentEnzymeAdhesinsFlagellaIronbindingproteinVirulencesurfaceproteinBacterialvirulencefactors〔細(xì)菌毒力因子〕第二十五頁,共69頁。Bacterialvirulence〔細(xì)菌的毒力〕Virulence(毒力)Invasiveness(侵襲力)Toxin(毒素)Adherence&permanentplanting(黏附與定植)Multiplication&diffusion(增殖與擴散)Anti-defensefunctionofhost(免疫逃逸)Endotoxin(內(nèi)毒素)Exotoxin(外毒素)第二十六頁,共69頁。Adhesionandfieldplanting〔黏附與定植〕Invasion〔侵入〕Multiplicationanddiffusion〔繁殖與擴散〕Localdiffusion〔部分?jǐn)U散〕Systemicdiffusion〔全身性擴散〕第二十七頁,共69頁?!颕nvasiveness〔侵襲力〕Definition:Bacterialcapabilitythatcanbreakthroughthephysiologicbarriers(skin,mucosa),settledown,multiply,andspreadinthehost.Adhesivefactors:adhesinandcapsuleInvasivesubstancesBacterialbiofilm第二十八頁,共69頁。1.Adhesin〔黏附素〕Protiensonbacterialsurfaceassociatedwithadhesion.Adhesinsbindtoadhesinreceptorsonhostcells.Classification:Pilus(fimbriae)adhesin(菌毛黏附素)Non-fimbriaeadhesin(非菌毛黏附素)第二十九頁,共69頁。AdhesinAdhesinEpitheliumReceptorBacterium第三十頁,共69頁。Capsule(莢膜)ofstreptococcuspneumoniaeMicrocapsule〔微莢膜〕Slimelayer〔黏液層〕第三十一頁,共69頁。ProtectthecellwallagainstattackbydrugsInhibitingestionandkillingbyphagocytesPlayaroleintheadherenceofhumantissueAntigenicity2.Capsule〔莢膜〕第三十二頁,共69頁。3.Invasiveenzymes侵襲性酶類Somebacteriamaygenerateinvasiveenzymes,whichcandamagebodytissuesandpromotetheinvasionanddiffusionofthebacteria.第三十三頁,共69頁。4.Invasin侵襲素Encodedbyinvasivegenes〔侵襲基因〕Mediateinvadingadjacentepithelialcells第三十四頁,共69頁。5.Bacterialbiofilm細(xì)菌生物被膜:Themembraneousbacterialcommunitycomposedofbacteriaandtheextracellularpolymerssecretedbybacteriaaftertheyadheretothesurfaceoflivingornonlivingmaterials.第三十五頁,共69頁。5.Bacterialbiofilm細(xì)菌生物被膜FacilitatesbacterialadhesionBafflesthepenetrationofantibioticandtherejectionofimmunesystemProfitssignalcommunicationamongbacteria.第三十六頁,共69頁。Bacterialbiofilm第三十七頁,共69頁。第三十八頁,共69頁。Biofilmintheendoscope〔內(nèi)窺鏡〕第三十九頁,共69頁。Staphylococcusepidermidis〔表皮葡萄球菌〕biofilminthesurfaceofvenouscatheter〔靜脈導(dǎo)管〕第四十頁,共69頁。ExotoxinsEndotoxinsExcretedbylivingcells;highconcentrationsinliquidmedium.IntegralpartofthecellwallofG-bacteria.Releasedonbacterialdeathandinpartduringgrowth.Maynotneedtobereleasedtohavebiologicactivity.ProducedbybothG+andG-bacteria.FoundonlyinG-bacteria.PolypeptidesLPS(lipidAportionprobablyresponsiblefortoxicity.)Relativelyunstable;toxicityoftendestroyedrapidlybyheatingattemperaturesabove60℃.Relativelystable;withstandheatingattemperaturesabove60℃forhourswithoutlossoftoxicity.第四十一頁,共69頁。ExotoxinsEndotoxinsHighlyantigenic;stimulateformationofhigh-titerantitoxin(抗毒素).Antitoxinneutralizestoxin.Weaklyimmunogenic;antibodiesareantitoxicandprotective.Relationshipbetweenantibodytitersandprotectionfromdiseaseislessclearthanwithexotoxins.Convertedtoantigenic,nontoxictoxoids(類毒素)byformalin,acid,heat,etc.Toxoidsareusedtoimmunize.Notconvertedtotoxoids.Highlytoxic;fataltoanimalsinmicrogramquantitiesorless.Moderatelytoxic;fatalforanimalsintenstohundredsofmicrograms.第四十二頁,共69頁。ExotoxinsEndotoxinsUsuallybindtospecificreceptorsoncells.Specificreceptorsnotfoundoncells.Usuallydonotproducefeverinthehost.Selectivetoxicityandspecificclinicalsyndromes.Neurotoxins(神經(jīng)毒素)Cytotoxins(細(xì)胞毒素)Enterotoxins(腸毒素)UsuallyproducefeverinthehostbyreleaseofIL-1andothermediators.Frequentlycontrolledbyextrachromosomalgenes(e.g.plasmids).Synthesisdirectedbychromosomalgenes.第四十三頁,共69頁。區(qū)別要點外毒素內(nèi)毒素來源革蘭陽性菌與部分革蘭陰性菌革蘭陰性菌編碼基因質(zhì)粒、前噬菌體或染色體基因染色體基因存在部分從活菌分泌出,少數(shù)菌崩解后釋出細(xì)胞壁組分,菌裂解后釋出化學(xué)成分蛋白質(zhì)脂多糖穩(wěn)定性60~80℃,30分鐘破壞160℃,2~4小時破壞毒性作用強,對組織器官有選擇性毒害效應(yīng),引起特殊的臨床表現(xiàn)較弱,各菌的毒性效應(yīng)大致相同,引起發(fā)熱、白細(xì)胞增多、微循環(huán)障礙、休克、DIC等抗原性強,刺激機體產(chǎn)生抗毒素;甲醛液處理脫毒形成類毒素弱,刺激機體產(chǎn)生的中和抗體作用弱;甲醛液不能脫毒形成類毒素第四十四頁,共69頁。SpecificpolysaccharideLPS第四十五頁,共69頁。Procedure第四十六頁,共69頁。Neurotoxin〔神經(jīng)毒素〕Tetanustoxin〔破傷風(fēng)毒素〕第四十七頁,共69頁。Cytotoxins〔細(xì)胞毒素〕Diphtheriatoxin〔白喉毒素〕inhibitsproteinsynthesisinmammaliancellsandcausesnecrosisofcellsDiphtheriamembraneonthroat第四十八頁,共69頁。Enterotoxin〔腸毒素〕Choleraenterotoxin第四十九頁,共69頁。BiologicalrolesofendotoxinFever〔發(fā)熱〕Leukopeniaandleukocytosis〔白細(xì)胞反響〕Endotoxemiaandshock〔內(nèi)毒素血癥與休克〕第五十頁,共69頁。EndotoxinActivatesmacrophagesActivatescomplementActivatesHagemanfactorIL-1,TNF,NitricoxideFeverandhypotensionC3a,C5aHypotensionEdemaCoagulationcascadeDIC第五十一頁,共69頁。Section4
theinitiationandprocessofinfectionSourcesofinfectionPathwayofbacterialentranceTypesofbacterialinfection第五十二頁,共69頁。Exogenousinfection〔外源性感染〕PatientsCarriers〔帶菌者〕AnimalsEnodogenousinfection〔內(nèi)源性感染〕OpportunisticpathogensSourcesofinfection第五十三頁,共69頁。Pathwayofpathogenentrance
RespiratoryGastrointestinalGenitalSkinandmucosaAnimalbitesBloodSexualtransmission第五十四頁,共69頁。TypesofbacterialinfectionInapparentinfection〔隱性感染〕Apparentinfection〔顯性感染〕Carrierstate〔帶菌狀態(tài)〕第五十五頁,共69頁。Inapparentinfection〔隱性感染〕Subclinicalinfection〔亞臨床型感染〕Aninfectionthathasnoobservablesymptoms.Itoccurswhenthehostimmunityispotentorthepathogenicityofthepathogenisweak.第五十六頁,共69頁。Thetipoftheiceberg
第五十七頁,共69頁。Apparentinfection〔顯性感染〕AcuteinfectionChronicinfectionLocalinfectionGeneralizedinfection★Toxemia(毒血癥)Endotoxemia(內(nèi)毒素血癥)Bacteremia(菌血癥)Septicemia(敗血癥)Pyemia(膿毒血癥)第五十八頁,共69頁。Toxemia〔毒血癥〕Bacteriamutiplyatinvadinglocationanddonotenterbloodstream,buttheexotoxins〔外毒素〕enterbloodandcausecorrespondingtoxicsymptoms.Endotoxemia〔內(nèi)毒素血癥〕Gram-negativebacteriamutiplyatlocationorinbloodstream,releasealotofamountendotoxin〔內(nèi)毒素〕releasedfrombacterialcellrupture.第五十九頁,共69頁。Bacteremia〔菌血癥〕Afterenteringblood,bacteriacirculatebutnotmultiplyintheblood.Septicemia〔敗血癥〕Bacteriacirculateandmultiplyintheblood,inwhichbacteriaproducetoxicproductsandcausehighswingingtypeoffeverandothertoxicsymptoms.第六十頁,共69頁。Pyemia〔膿毒血癥〕Pyogenic〔化膿性〕bacteriaproducesepticemiawithmultipleabscesses〔膿腫〕ininternalorganssuchasspleen,liverandkidneys.第六十一頁,共69頁?!顲arrierstate〔帶菌狀態(tài)〕Afterinapparentinfectionorapparentinfection,sometimesthepathogensarenoteliminatedintime,sothebacteriawillsurviveandmultiplyinhostatlowspeed,andbacteriaspreadintotheenvironment.Carrier〔帶菌者〕isimportantsourceofinfection.第六十二頁,共69頁。HospitalinfectionDefinitionBasiccharacteristicsClassificationMicrobialecologicalcharacteristicsEpidemiolog
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