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Chapter6

Bacterialinfectionandimmunity

细菌的感染与免疫第一页,共69页。BasictermsBacterialinfection〔细菌的感染〕Pathogen〔病原菌〕Nonpathogen〔非病原菌〕Opportunisticpathogen〔时机致病菌〕第二页,共69页。BacterialInfection细菌的感染Theprocessofbacteriainvadinginthebody,growinginthetissues,producingtoxinsandcausingdiseasesiscalledbacterialinfection.第三页,共69页。Pathogen〔病原菌〕Pathogenicbacterium〔致病菌〕Abacteriumwhichcancauseadiseaseiscalledpathogen.Nonpathogen〔非病原菌〕Nonpathogenicbacterium〔非致病菌〕Abacteriumthatdoesnotcausediseaseiscallednonpathogen.第四页,共69页。Opportunisticpathogen〔时机致病菌〕Conditionedpathogen〔条件致病菌〕Somebacteriaarecapableofcausingdiseasesonlyundercertainconditions.Theseorganismscancausediseaseonlyifoneormoreoftheusualdefencemechanismshumanshaveevolvedtorestrictmicroorganismsfromtheirusuallysterileinternalorgansandtissuearebreachedbyaccident,byintent(e.g.surgery),orbyanunderlyingmetabolicoraninfectiousdisorder(e.g.AIDS).第五页,共69页。OutlineNormalfloraandopportunisticpathogenBacterialpathogenesisThehostimmunedefencesystemTheinitiationandcourseofinfectionHospitalinfection第六页,共69页。Section1

Normalfloraandopportunisticpathogen

正常菌群与时机致病菌第七页,共69页。★Normalflora〔正常菌群〕Normalmicrobialflora〔正常微生物群〕Thepopulationofmicroorganismsthatinhabittheskinandmucousmembranesofhealthypersons.Theyareusuallyharmless,someevenbeneficial,tohuman’shealth.第八页,共69页。LocationsSurfacetissuesofskinOralcavityRespiratorytractGastrointestinaltractGenitourinarytract第九页,共69页。Normalfloraonintestinalmucosa第十页,共69页。肠道的正常菌群第十一页,共69页。第十二页,共69页。★BeneficialeffectsofthenormalfloraBiologicalantagonism〔生物拮抗〕Productionofessentialnutrients〔营养作用〕Primingofimmunesystem〔免疫作用〕Anti-aging〔抗衰老作用〕第十三页,共69页。Biologicalantagonism(生物拮抗)Biologicalbarriers〔生物屏障〕orReceptorcompetition〔受体竞争)Harmfulmetabolites〔有害代谢产物〕Nutrientcompetition〔营养竞争〕第十四页,共69页。Conditionedpathogen〔条件致病菌〕Somebacteriaarecapableofcausingdiseasesonlyundercertainconditions.Thesebacteriaarecalledopportunistic(conditioned)pathogensandthiskindofinfectioniscalledopportunisticinfection〔时机性感染〕.★Opportunisticpathogen〔时机致病菌〕第十五页,共69页。★

ConditionsofopportunisticinfectionChangeofinhabitingplaces〔寄居部位改变〕Immunesystemcompromise〔宿主免疫功能低下〕Dysbacteriosis〔菌群失调〕第十六页,共69页。Dysbacteriosis〔菌群失调〕Iffloradisequilibriumoccurs,forexample,whentheresidentfloraisdisturbed,somelittlesignificantmicroorganismsmaycolonize,proliferate,andproducedisease,whichiscalleddysbacteriosis.Dysbacteriosismainlyresultedfromlongtermandlargedosesantibioticstaken.第十七页,共69页。Superinfection〔重叠感染〕Afrequentcomplicationofdrugtherapyformicrobialinfection.Itmayresultfromopportunisticcolonizationfollowingimmunosuppressionbytheprimarypathogenandcanbeinfluencedbythetimeintervalbetweeninfections,microbialphysiology,orhostresistance.第十八页,共69页。Dysbacteriosisandsuperinfection第十九页,共69页。肠道的正常菌群安康青壮年粪便涂片安康老年粪便涂片〔双歧杆菌〕第二十页,共69页。Probiotics〔益生菌〕第二十一页,共69页。Probiotics〔益生菌〕&Prebiotics〔益生元〕第二十二页,共69页。Section2

BacterialPathogenesis

细菌的致病作用BasictermsBacterialPathogenicity

BacterialvirulenceNumberofinvadingorganismsPortalofentry第二十三页,共69页。Pathogenicity〔致病性〕isusedtodescribethecapacityofbacteriatoinitiatediseases.Thetermofvirulence〔毒力〕isusedasacomparisonofpathogenicityinthequantitativesense.ID50〔medianinfectiousdose,半数感染量〕:Infectiousdoseofbacteriafor50%ofthetestpopulation.LD50〔medianlethaldose,半数致死量〕:Lethaldoseofbacteriafor50%ofthetestpopulation.BasicTerms第二十四页,共69页。ExotoxinPili(Fimbrial)CapsuleVirulentEnzymeAdhesinsFlagellaIronbindingproteinVirulencesurfaceproteinBacterialvirulencefactors〔细菌毒力因子〕第二十五页,共69页。Bacterialvirulence〔细菌的毒力〕Virulence(毒力)Invasiveness(侵袭力)Toxin(毒素)Adherence&permanentplanting(黏附与定植)Multiplication&diffusion(增殖与扩散)Anti-defensefunctionofhost(免疫逃逸)Endotoxin(内毒素)Exotoxin(外毒素)第二十六页,共69页。Adhesionandfieldplanting〔黏附与定植〕Invasion〔侵入〕Multiplicationanddiffusion〔繁殖与扩散〕Localdiffusion〔部分扩散〕Systemicdiffusion〔全身性扩散〕第二十七页,共69页。★Invasiveness〔侵袭力〕Definition:Bacterialcapabilitythatcanbreakthroughthephysiologicbarriers(skin,mucosa),settledown,multiply,andspreadinthehost.Adhesivefactors:adhesinandcapsuleInvasivesubstancesBacterialbiofilm第二十八页,共69页。1.Adhesin〔黏附素〕Protiensonbacterialsurfaceassociatedwithadhesion.Adhesinsbindtoadhesinreceptorsonhostcells.Classification:Pilus(fimbriae)adhesin(菌毛黏附素)Non-fimbriaeadhesin(非菌毛黏附素)第二十九页,共69页。AdhesinAdhesinEpitheliumReceptorBacterium第三十页,共69页。Capsule(荚膜)ofstreptococcuspneumoniaeMicrocapsule〔微荚膜〕Slimelayer〔黏液层〕第三十一页,共69页。ProtectthecellwallagainstattackbydrugsInhibitingestionandkillingbyphagocytesPlayaroleintheadherenceofhumantissueAntigenicity2.Capsule〔荚膜〕第三十二页,共69页。3.Invasiveenzymes侵袭性酶类Somebacteriamaygenerateinvasiveenzymes,whichcandamagebodytissuesandpromotetheinvasionanddiffusionofthebacteria.第三十三页,共69页。4.Invasin侵袭素Encodedbyinvasivegenes〔侵袭基因〕Mediateinvadingadjacentepithelialcells第三十四页,共69页。5.Bacterialbiofilm细菌生物被膜:Themembraneousbacterialcommunitycomposedofbacteriaandtheextracellularpolymerssecretedbybacteriaaftertheyadheretothesurfaceoflivingornonlivingmaterials.第三十五页,共69页。5.Bacterialbiofilm细菌生物被膜FacilitatesbacterialadhesionBafflesthepenetrationofantibioticandtherejectionofimmunesystemProfitssignalcommunicationamongbacteria.第三十六页,共69页。Bacterialbiofilm第三十七页,共69页。第三十八页,共69页。Biofilmintheendoscope〔内窥镜〕第三十九页,共69页。Staphylococcusepidermidis〔表皮葡萄球菌〕biofilminthesurfaceofvenouscatheter〔静脉导管〕第四十页,共69页。ExotoxinsEndotoxinsExcretedbylivingcells;highconcentrationsinliquidmedium.IntegralpartofthecellwallofG-bacteria.Releasedonbacterialdeathandinpartduringgrowth.Maynotneedtobereleasedtohavebiologicactivity.ProducedbybothG+andG-bacteria.FoundonlyinG-bacteria.PolypeptidesLPS(lipidAportionprobablyresponsiblefortoxicity.)Relativelyunstable;toxicityoftendestroyedrapidlybyheatingattemperaturesabove60℃.Relativelystable;withstandheatingattemperaturesabove60℃forhourswithoutlossoftoxicity.第四十一页,共69页。ExotoxinsEndotoxinsHighlyantigenic;stimulateformationofhigh-titerantitoxin(抗毒素).Antitoxinneutralizestoxin.Weaklyimmunogenic;antibodiesareantitoxicandprotective.Relationshipbetweenantibodytitersandprotectionfromdiseaseislessclearthanwithexotoxins.Convertedtoantigenic,nontoxictoxoids(类毒素)byformalin,acid,heat,etc.Toxoidsareusedtoimmunize.Notconvertedtotoxoids.Highlytoxic;fataltoanimalsinmicrogramquantitiesorless.Moderatelytoxic;fatalforanimalsintenstohundredsofmicrograms.第四十二页,共69页。ExotoxinsEndotoxinsUsuallybindtospecificreceptorsoncells.Specificreceptorsnotfoundoncells.Usuallydonotproducefeverinthehost.Selectivetoxicityandspecificclinicalsyndromes.Neurotoxins(神经毒素)Cytotoxins(细胞毒素)Enterotoxins(肠毒素)UsuallyproducefeverinthehostbyreleaseofIL-1andothermediators.Frequentlycontrolledbyextrachromosomalgenes(e.g.plasmids).Synthesisdirectedbychromosomalgenes.第四十三页,共69页。区别要点外毒素内毒素来源革兰阳性菌与部分革兰阴性菌革兰阴性菌编码基因质粒、前噬菌体或染色体基因染色体基因存在部分从活菌分泌出,少数菌崩解后释出细胞壁组分,菌裂解后释出化学成分蛋白质脂多糖稳定性60~80℃,30分钟破坏160℃,2~4小时破坏毒性作用强,对组织器官有选择性毒害效应,引起特殊的临床表现较弱,各菌的毒性效应大致相同,引起发热、白细胞增多、微循环障碍、休克、DIC等抗原性强,刺激机体产生抗毒素;甲醛液处理脱毒形成类毒素弱,刺激机体产生的中和抗体作用弱;甲醛液不能脱毒形成类毒素第四十四页,共69页。SpecificpolysaccharideLPS第四十五页,共69页。Procedure第四十六页,共69页。Neurotoxin〔神经毒素〕Tetanustoxin〔破伤风毒素〕第四十七页,共69页。Cytotoxins〔细胞毒素〕Diphtheriatoxin〔白喉毒素〕inhibitsproteinsynthesisinmammaliancellsandcausesnecrosisofcellsDiphtheriamembraneonthroat第四十八页,共69页。Enterotoxin〔肠毒素〕Choleraenterotoxin第四十九页,共69页。BiologicalrolesofendotoxinFever〔发热〕Leukopeniaandleukocytosis〔白细胞反响〕Endotoxemiaandshock〔内毒素血症与休克〕第五十页,共69页。EndotoxinActivatesmacrophagesActivatescomplementActivatesHagemanfactorIL-1,TNF,NitricoxideFeverandhypotensionC3a,C5aHypotensionEdemaCoagulationcascadeDIC第五十一页,共69页。Section4

theinitiationandprocessofinfectionSourcesofinfectionPathwayofbacterialentranceTypesofbacterialinfection第五十二页,共69页。Exogenousinfection〔外源性感染〕PatientsCarriers〔带菌者〕AnimalsEnodogenousinfection〔内源性感染〕OpportunisticpathogensSourcesofinfection第五十三页,共69页。Pathwayofpathogenentrance

RespiratoryGastrointestinalGenitalSkinandmucosaAnimalbitesBloodSexualtransmission第五十四页,共69页。TypesofbacterialinfectionInapparentinfection〔隐性感染〕Apparentinfection〔显性感染〕Carrierstate〔带菌状态〕第五十五页,共69页。Inapparentinfection〔隐性感染〕Subclinicalinfection〔亚临床型感染〕Aninfectionthathasnoobservablesymptoms.Itoccurswhenthehostimmunityispotentorthepathogenicityofthepathogenisweak.第五十六页,共69页。Thetipoftheiceberg

第五十七页,共69页。Apparentinfection〔显性感染〕AcuteinfectionChronicinfectionLocalinfectionGeneralizedinfection★Toxemia(毒血症)Endotoxemia(内毒素血症)Bacteremia(菌血症)Septicemia(败血症)Pyemia(脓毒血症)第五十八页,共69页。Toxemia〔毒血症〕Bacteriamutiplyatinvadinglocationanddonotenterbloodstream,buttheexotoxins〔外毒素〕enterbloodandcausecorrespondingtoxicsymptoms.Endotoxemia〔内毒素血症〕Gram-negativebacteriamutiplyatlocationorinbloodstream,releasealotofamountendotoxin〔内毒素〕releasedfrombacterialcellrupture.第五十九页,共69页。Bacteremia〔菌血症〕Afterenteringblood,bacteriacirculatebutnotmultiplyintheblood.Septicemia〔败血症〕Bacteriacirculateandmultiplyintheblood,inwhichbacteriaproducetoxicproductsandcausehighswingingtypeoffeverandothertoxicsymptoms.第六十页,共69页。Pyemia〔脓毒血症〕Pyogenic〔化脓性〕bacteriaproducesepticemiawithmultipleabscesses〔脓肿〕ininternalorganssuchasspleen,liverandkidneys.第六十一页,共69页。★Carrierstate〔带菌状态〕Afterinapparentinfectionorapparentinfection,sometimesthepathogensarenoteliminatedintime,sothebacteriawillsurviveandmultiplyinhostatlowspeed,andbacteriaspreadintotheenvironment.Carrier〔带菌者〕isimportantsourceofinfection.第六十二页,共69页。HospitalinfectionDefinitionBasiccharacteristicsClassificationMicrobialecologicalcharacteristicsEpidemiolog

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