Chapter6

Bacterialinfectionandimmunity

細菌的感染與免疫第一頁，共69頁。BasictermsBacterialinfection〔細菌的感染〕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。★Normalflora〔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。★BeneficialeffectsofthenormalfloraBiologicalantagonism〔生物拮抗〕Productionofessentialnutrients〔營養作用〕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〔有害代謝產物〕Nutrientcompetition〔營養競爭〕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。★

ConditionsofopportunisticinfectionChangeofinhabitingplaces〔寄居部位改變〕Immunesystemcompromise〔宿主免疫功能低下〕Dysbacteriosis〔菌群失調〕第十六頁，共69頁。Dysbacteriosis〔菌群失調〕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,半數感染量〕:Infectiousdoseofbacteriafor50%ofthetestpopulation.LD50〔medianlethaldose,半數致死量〕:Lethaldoseofbacteriafor50%ofthetestpopulation.BasicTerms第二十四頁，共69頁。ExotoxinPili(Fimbrial)CapsuleVirulentEnzymeAdhesinsFlagellaIronbindingproteinVirulencesurfaceproteinBacterialvirulencefactors〔細菌毒力因子〕第二十五頁，共69頁。Bacterialvirulence〔細菌的毒力〕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〔部分擴散〕Systemicdiffusion〔全身性擴散〕第二十七頁，共69頁。★Invasiveness〔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細菌生物被膜：Themembraneousbacterialcommunitycomposedofbacteriaandtheextracellularpolymerssecretedbybacteriaaftertheyadheretothesurfaceoflivingornonlivingmaterials.第三十五頁，共69頁。5.Bacterialbiofilm細菌生物被膜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〔內窺鏡〕第三十九頁，共69頁。Staphylococcusepidermidis〔表皮葡萄球菌〕biofilminthesurfaceofvenouscatheter〔靜脈導管〕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(神經毒素)Cytotoxins(細胞毒素)Enterotoxins(腸毒素)UsuallyproducefeverinthehostbyreleaseofIL-1andothermediators.Frequentlycontrolledbyextrachromosomalgenes(e.g.plasmids).Synthesisdirectedbychromosomalgenes.第四十三頁，共69頁。區別要點外毒素內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，少數菌崩解后釋出細胞壁組分，菌裂解后釋出化學成分蛋白質脂多糖穩定性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，引起特殊的臨床表現較弱，各菌的毒性效應大致相同，引起發熱、白細胞增多、微循環障礙、休克、DIC等抗原性強，刺激機體產生抗毒素；甲醛液處理脫毒形成類毒素弱，刺激機體產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〔神經毒素〕Tetanustoxin〔破傷風毒素〕第四十七頁，共69頁。Cytotoxins〔細胞毒素〕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〔發熱〕Leukopeniaandleukocytosis〔白細胞反響〕Endotoxemiaandshock〔內毒素血癥與休克〕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〕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〔內毒素血癥〕Gram-negativebacteriamutiplyatlocationorinbloodstream,releasealotofamountendotoxin〔內毒素〕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。★Carrierstate〔帶菌狀態〕Afterinapparentinfectionorapparentinfection,sometimesthepathogensarenoteliminatedintime,sothebacteriawillsurviveandmultiplyinhostatlowspeed,andbacteriaspreadintotheenvironment.Carrier〔帶菌者〕isimportantsourceofinfection.第六十二頁，共69頁。HospitalinfectionDefinitionBasiccharacteristicsClassificationMicrobialecologicalcharacteristicsEpidemiolog