雙語細(xì)菌的感染與免疫

BasictermsBacterialinfection（細(xì)菌的感染）Pathogen（病原菌）Nonpathogen（非病原菌）Opportunisticpathogen（機(jī)會(huì)致病菌）當(dāng)前第1頁\共有68頁\編于星期四\16點(diǎn)BacterialInfection細(xì)菌的感染Theprocessofbacteriainvadinginthebody,growinginthetissues,producingtoxinsandcausingdiseasesiscalledbacterialinfection.當(dāng)前第2頁\共有68頁\編于星期四\16點(diǎn)Pathogen（病原菌）Pathogenicbacterium（致病菌）Abacteriumwhichcancauseadiseaseiscalledpathogen.Nonpathogen（非病原菌）Nonpathogenicbacterium（非致病菌）Abacteriumthatdoesnotcausediseaseiscallednonpathogen.當(dāng)前第3頁\共有68頁\編于星期四\16點(diǎn)Opportunisticpathogen（機(jī)會(huì)致病菌）Conditionedpathogen（條件致病菌）Somebacteriaarecapableofcausingdiseasesonlyundercertainconditions.Theseorganismscancausediseaseonlyifoneormoreoftheusualdefencemechanismshumanshaveevolvedtorestrictmicroorganismsfromtheirusuallysterileinternalorgansandtissuearebreachedbyaccident,byintent(e.g.surgery),orbyanunderlyingmetabolicoraninfectiousdisorder(e.g.AIDS).當(dāng)前第4頁\共有68頁\編于星期四\16點(diǎn)OutlineNormalfloraandopportunisticpathogenBacterialpathogenesisThehostimmunedefencesystemTheinitiationandcourseofinfectionHospitalinfection當(dāng)前第5頁\共有68頁\編于星期四\16點(diǎn)Section1

Normalfloraandopportunisticpathogen

正常菌群與機(jī)會(huì)致病菌當(dāng)前第6頁\共有68頁\編于星期四\16點(diǎn)★Normalflora（正常菌群）Normalmicrobialflora（正常微生物群）Thepopulationofmicroorganismsthatinhabittheskinandmucousmembranesofhealthypersons.Theyareusuallyharmless,someevenbeneficial,tohuman’shealth.當(dāng)前第7頁\共有68頁\編于星期四\16點(diǎn)LocationsSurfacetissuesofskinOralcavityRespiratorytractGastrointestinaltractGenitourinarytract當(dāng)前第8頁\共有68頁\編于星期四\16點(diǎn)Normalfloraonintestinalmucosa當(dāng)前第9頁\共有68頁\編于星期四\16點(diǎn)腸道的正常菌群當(dāng)前第10頁\共有68頁\編于星期四\16點(diǎn)當(dāng)前第11頁\共有68頁\編于星期四\16點(diǎn)★BeneficialeffectsofthenormalfloraBiologicalantagonism（生物拮抗）Productionofessentialnutrients（營養(yǎng)作用）Primingofimmunesystem（免疫作用）Anti-aging（抗衰老作用）當(dāng)前第12頁\共有68頁\編于星期四\16點(diǎn)Biologicalantagonism(生物拮抗)Biologicalbarriers（生物屏障）orReceptorcompetition（受體競(jìng)爭(zhēng))Harmfulmetabolites（有害代謝產(chǎn)物）Nutrientcompetition（營養(yǎng)競(jìng)爭(zhēng)）當(dāng)前第13頁\共有68頁\編于星期四\16點(diǎn)Conditionedpathogen（條件致病菌）Somebacteriaarecapableofcausingdiseasesonlyundercertainconditions.Thesebacteriaarecalledopportunistic(conditioned)pathogensandthiskindofinfectioniscalledopportunisticinfection（機(jī)會(huì)性感染）.★

Opportunisticpathogen（機(jī)會(huì)致病菌）當(dāng)前第14頁\共有68頁\編于星期四\16點(diǎn)★

ConditionsofopportunisticinfectionChangeofinhabitingplaces（寄居部位改變）Immunesystemcompromise（宿主免疫功能低下）Dysbacteriosis（菌群失調(diào)）當(dāng)前第15頁\共有68頁\編于星期四\16點(diǎn)Dysbacteriosis（菌群失調(diào)）Iffloradisequilibriumoccurs,forexample,whentheresidentfloraisdisturbed,somelittlesignificantmicroorganismsmaycolonize,proliferate,andproducedisease,whichiscalleddysbacteriosis.Dysbacteriosismainlyresultedfromlongtermandlargedosesantibioticstaken.當(dāng)前第16頁\共有68頁\編于星期四\16點(diǎn)Superinfection（重疊感染）Afrequentcomplicationofdrugtherapyformicrobialinfection.Itmayresultfromopportunisticcolonizationfollowingimmunosuppressionbytheprimarypathogenandcanbeinfluencedbythetimeintervalbetweeninfections,microbialphysiology,orhostresistance.當(dāng)前第17頁\共有68頁\編于星期四\16點(diǎn)Dysbacteriosisandsuperinfection當(dāng)前第18頁\共有68頁\編于星期四\16點(diǎn)腸道的正常菌群健康青壯年糞便涂片健康老年糞便涂片（雙歧桿菌）當(dāng)前第19頁\共有68頁\編于星期四\16點(diǎn)Probiotics（益生菌）當(dāng)前第20頁\共有68頁\編于星期四\16點(diǎn)Probiotics（益生菌）&Prebiotics（益生元）當(dāng)前第21頁\共有68頁\編于星期四\16點(diǎn)Section2

BacterialPathogenesis

細(xì)菌的致病作用BasictermsBacterialPathogenicity

BacterialvirulenceNumberofinvadingorganismsPortalofentry當(dāng)前第22頁\共有68頁\編于星期四\16點(diǎn)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當(dāng)前第23頁\共有68頁\編于星期四\16點(diǎn)ExotoxinPili(Fimbrial)CapsuleVirulentEnzymeAdhesinsFlagellaIronbindingproteinVirulencesurfaceproteinBacterialvirulencefactors（細(xì)菌毒力因子）當(dāng)前第24頁\共有68頁\編于星期四\16點(diǎn)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(kuò)散）Anti-defensefunctionofhost（免疫逃逸）Endotoxin（內(nèi)毒素）Exotoxin（外毒素）當(dāng)前第25頁\共有68頁\編于星期四\16點(diǎn)Adhesionandfieldplanting（黏附與定植）Invasion（侵入）Multiplicationanddiffusion（繁殖與擴(kuò)散）Localdiffusion（局部擴(kuò)散）Systemicdiffusion（全身性擴(kuò)散）當(dāng)前第26頁\共有68頁\編于星期四\16點(diǎn)★Invasiveness（侵襲力）Definition:Bacterialcapabilitythatcanbreakthroughthephysiologicbarriers(skin,mucosa),settledown,multiply,andspreadinthehost.Adhesivefactors:adhesinandcapsuleInvasivesubstancesBacterialbiofilm當(dāng)前第27頁\共有68頁\編于星期四\16點(diǎn)1.Adhesin（黏附素）Protiensonbacterialsurfaceassociatedwithadhesion.Adhesinsbindtoadhesinreceptorsonhostcells.Classification:Pilus(fimbriae)adhesin(菌毛黏附素)Non-fimbriaeadhesin(非菌毛黏附素)當(dāng)前第28頁\共有68頁\編于星期四\16點(diǎn)AdhesinAdhesinEpitheliumReceptorBacterium當(dāng)前第29頁\共有68頁\編于星期四\16點(diǎn)Capsule(莢膜)ofstreptococcuspneumoniaeMicrocapsule（微莢膜）

Slimelayer（黏液層）當(dāng)前第30頁\共有68頁\編于星期四\16點(diǎn)ProtectthecellwallagainstattackbydrugsInhibitingestionandkillingbyphagocytesPlayaroleintheadherenceofhumantissueAntigenicity2.Capsule（莢膜）當(dāng)前第31頁\共有68頁\編于星期四\16點(diǎn)3.Invasiveenzymes侵襲性酶類Somebacteriamaygenerateinvasiveenzymes,whichcandamagebodytissuesandpromotetheinvasionanddiffusionofthebacteria.當(dāng)前第32頁\共有68頁\編于星期四\16點(diǎn)4.Invasin侵襲素Encodedbyinvasivegenes（侵襲基因）Mediateinvadingadjacentepithelialcells當(dāng)前第33頁\共有68頁\編于星期四\16點(diǎn)5.Bacterialbiofilm細(xì)菌生物被膜：Themembraneousbacterialcommunitycomposedofbacteriaandtheextracellularpolymerssecretedbybacteriaaftertheyadheretothesurfaceoflivingornonlivingmaterials.當(dāng)前第34頁\共有68頁\編于星期四\16點(diǎn)5.Bacterialbiofilm細(xì)菌生物被膜FacilitatesbacterialadhesionBafflesthepenetrationofantibioticandtherejectionofimmunesystemProfitssignalcommunicationamongbacteria.當(dāng)前第35頁\共有68頁\編于星期四\16點(diǎn)Bacterialbiofilm當(dāng)前第36頁\共有68頁\編于星期四\16點(diǎn)當(dāng)前第37頁\共有68頁\編于星期四\16點(diǎn)Biofilmintheendoscope（內(nèi)窺鏡）當(dāng)前第38頁\共有68頁\編于星期四\16點(diǎn)Staphylococcusepidermidis（表皮葡萄球菌）biofilminthesurfaceofvenouscatheter（靜脈導(dǎo)管）當(dāng)前第39頁\共有68頁\編于星期四\16點(diǎn)ExotoxinsEndotoxinsExcretedbylivingcells;highconcentrationsinliquidmedium.IntegralpartofthecellwallofG-bacteria.Releasedonbacterialdeathandinpartduringgrowth.Maynotneedtobereleasedtohavebiologicactivity.ProducedbybothG+andG-bacteria.FoundonlyinG-bacteria.PolypeptidesLPS(lipidAportionprobablyresponsiblefortoxicity.)Relativelyunstable;toxicityoftendestroyedrapidlybyheatingattemperaturesabove60℃.Relativelystable;withstandheatingattemperaturesabove60℃forhourswithoutlossoftoxicity.當(dāng)前第40頁\共有68頁\編于星期四\16點(diǎn)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.當(dāng)前第41頁\共有68頁\編于星期四\16點(diǎn)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.當(dāng)前第42頁\共有68頁\編于星期四\16點(diǎn)區(qū)別要點(diǎn)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(shí)破壞毒性作用強(qiáng)，對(duì)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(qiáng)，刺激機(jī)體產(chǎn)生抗毒素；甲醛液處理脫毒形成類毒素弱，刺激機(jī)體產(chǎn)生的中和抗體作用弱；甲醛液不能脫毒形成類毒素當(dāng)前第43頁\共有68頁\編于星期四\16點(diǎn)SpecificpolysaccharideLPS當(dāng)前第44頁\共有68頁\編于星期四\16點(diǎn)Procedure當(dāng)前第45頁\共有68頁\編于星期四\16點(diǎn)Neurotoxin（神經(jīng)毒素）Tetanustoxin（破傷風(fēng)毒素）當(dāng)前第46頁\共有68頁\編于星期四\16點(diǎn)Cytotoxins（細(xì)胞毒素）Diphtheriatoxin（白喉毒素）inhibitsproteinsynthesisinmammaliancellsandcausesnecrosisofcellsDiphtheriamembraneonthroat當(dāng)前第47頁\共有68頁\編于星期四\16點(diǎn)Enterotoxin（腸毒素）Choleraenterotoxin當(dāng)前第48頁\共有68頁\編于星期四\16點(diǎn)BiologicalrolesofendotoxinFever（發(fā)熱）Leukopeniaandleukocytosis（白細(xì)胞反應(yīng)）Endotoxemiaandshock（內(nèi)毒素血癥與休克）當(dāng)前第49頁\共有68頁\編于星期四\16點(diǎn)EndotoxinActivatesmacrophagesActivatescomplementActivatesHagemanfactorIL-1,TNF,NitricoxideFeverandhypotensionC3a,C5aHypotensionEdemaCoagulationcascadeDIC當(dāng)前第50頁\共有68頁\編于星期四\16點(diǎn)Section4

theinitiationandprocessofinfectionSourcesofinfectionPathwayofbacterialentranceTypesofbacterialinfection當(dāng)前第51頁\共有68頁\編于星期四\16點(diǎn)Exogenousinfection（外源性感染）PatientsCarriers（帶菌者）AnimalsEnodogenousinfection（內(nèi)源性感染）OpportunisticpathogensSourcesofinfection當(dāng)前第52頁\共有68頁\編于星期四\16點(diǎn)Pathwayofpathogenentrance

RespiratoryGastrointestinalGenitalSkinandmucosaAnimalbitesBloodSexualtransmission當(dāng)前第53頁\共有68頁\編于星期四\16點(diǎn)TypesofbacterialinfectionInapparentinfection（隱性感染）Apparentinfection（顯性感染）Carrierstate（帶菌狀態(tài)）當(dāng)前第54頁\共有68頁\編于星期四\16點(diǎn)Inapparentinfection（隱性感染）Subclinicalinfection（亞臨床型感染）Aninfectionthathasnoobservablesymptoms.Itoccurswhenthehostimmunityispotentorthepathogenicityofthepathogenisweak.當(dāng)前第55頁\共有68頁\編于星期四\16點(diǎn)Thetipoftheiceberg

當(dāng)前第56頁\共有68頁\編于星期四\16點(diǎn)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)當(dāng)前第57頁\共有68頁\編于星期四\16點(diǎn)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.當(dāng)前第58頁\共有68頁\編于星期四\16點(diǎn)Bacteremia（菌血癥）Afterenteringblood,bacteriacirculatebutnotmultiplyintheblood.Septicemia（敗血癥）Bacteriacirculateandmultiplyintheblood,inwhichbacteriaproducetoxicproductsandcausehighswingingtypeoffeverandothertoxicsymptoms.當(dāng)前第59頁\共有68頁\編于星期四\16點(diǎn)Pyemia（膿毒血癥）Pyogenic（化膿性）bacteriaproducesepticemiawithmultipleabscesses（膿腫）ininternalorganssuchasspleen,liverandkidneys.當(dāng)前第60頁\共有68頁\編于星期四\16點(diǎn)★

Carrierstate（帶菌狀態(tài)）Afterinapparentinfectionorapparentinfection,sometimesthepathogensarenoteliminatedintime,sothebacteriawillsurviveandmultiplyinhostatlowspeed,andbacteriaspreadintotheenvironment.Carrier（帶菌者）isimportantsourceofinfection.當(dāng)前第61頁\共有68頁\編于星期四\16點(diǎn)HospitalinfectionDefinitionBasiccharacteristicsClassificationMicrobialecologicalcharacteristicsEpidemiologicalc