第五章細(xì)菌感染與免疫七年制

Chapter5BacterialInfectionandImmunitySection1

NormalfloraandOpportunisticpathogen

normalflorathemicroorganismthatparasitizeonthebodysurfaceortractsconnectingwithexternal,don’tharmthehostinordinarycondition.I.

Distributionofnormalfloraskinoralcavity:anaerobesintestinaltract:anaerobes:aerobes=1000:1vagina:Lactobacillus.respiratoryII.Roleofnormalflora1.biologicalbarrier:antagonism2.

nutrientsynthesize:aminoacid,VB,Vk3.

immunity:enhanceanddevelopandmaturationofimmunesystem4.removalofharmfulsubstances5.anti-aging6.anti-tumorOpportunisticpathogensomebacteriaareunabletocauseinfectioninordinarycondition,butcaninitiateinfectionundersomecertaincondition.NormalfloraOpportunisticpathogenconditionopportunisticpathogenIf:(1)hostimmunityreduce(2)dysbacteriosisbalanceofnormalflorawasbroken(3)translocationnormalfloraleavetheirordinaryhabitantandgainaccesstootherpart

Section2BacterialPathogenesisMechanismvirulence:referstoextent(thedegree)ofpathogenicitymedianlethaldose(LD50):ThenumberofpathogensrequiredtocauselethaldiseaseinhalfoftheexposedhostsiscalledanLD50.medianinfectivedose(ID50):Thenumberofpathogensrequiredtocausedisease(or,atleast,infection)inhalfoftheexposedhostsiscalledtheID50.InfectionandDisease

virulenceofbacteriatheamountofinvadingbacteriatheportalofentrytheimmunityofhostVirulence

surfacestructureinvasivesubstanceexotoxinendotoxininvasivenesstoxinimmuneescape(I)Invasiveness：Theabilityofbacteriatoresisthostdefence,colonize,multiplyandspread.

1.adherencefactors------surfacestructurebacteriatohostcell:pili(/flagella)capsulelipoteichoicacidcolonizationfactorbacteriatobacteria:microcolonybiofilm2.Penetrationandspreadinvasininvasiveenzyme---exoenzymecoagulase---S.aureusfibrinogen→fibrin→surroundbacteriahyaluronidase(spreadingfactor)hydrolyzehyaluronicacid→tissueloose→B.spreadsstreptokinase.SK----Lysefibrin→B.spreadsimmuneescapecapsule---anti-phagocytosisIgAprotease---cleavelocalIgA(II).toxin1.exotoxin：excretedbylivingcells,G+bacteria(most)polypeptideheat-unstable,60℃,1-2hrdestroystrongantigenicity，exotoxin→toxoidhighlytoxichighselectionfortissues

structure:Asubunit-BsubunitneurotoxincytotoxinenterotoxinexotoxinsubunitA：toxicityactivesubunitB:non-toxicity,bindreceptorofsensitivecellexotoxinneurotoxin：tetanospasminspinalcordcytotoxin:diphtherotoxininhibitcellproteinsynthesisenterotoxin:choleratoxin

Aseverecaseoftetanus.muscles,backandlegsarerigidmusclespasmscanbreakbonescanbefatal(e.grespiratoryfalure)ClostridiumtetaniVibriocholeraBGM1ANa+,Cl-adenylatecyclaseATP→cAMPNa+,Cl-,H2OThischildhasdiphtheriaresultinginathickgray

coatingoverbackofthroat.Thiscoatingcaneventuallyexpanddownthroughairwayand,ifnottreated,thechildcoulddiefromsuffocationCorynebacterium–Diphtheria2.endotoxinintegralpartofG－bacteriacellwall.releaseafterbacteriadisintegrationLPS,maintoxicpart:LipidAheat-stable:160℃2-4hrcan’tconvertedintotoxoidweaklytoxicnon-specificityallendotoxinsproducethesamesymptoms.feverWBCreactionendotoxemiaandshockShwartzmanandDICSection3BacterialInfectionOriginofinfection1.

Exogenousinfection(1)

patient(2)

carrier(3)animal2.

EndogenousinfectionnormalfloradysbacteriosisVerticaltransmissionHorizontaltransmissionpersonpersonanimalmotheroffspringplacentabirthcanalbreastmilk(zoonosis)Themodeofinfection1.

damagedskinormucousmembranes2.

respiratorytract3.digestivetract4.genitalandurinarytractⅠ.inapparentinfectionII.apparentinfection

Thetypeofinfectionapparentinfectionacuteinfectionlocalinfectionchronicinfectionsystemicinfection

furunclecarbunclebacteremiatoxemiasepticemiapyemiawholebodyinfectionbacteremia:isaninvasionofthebloodstreambybacteria.toxemia:isthepresenceofexotoxinintheblood.endotoxemia:isthepresenceofendotoxinintheblood.septicemia:illnessthatoccurswhenpoisonoussubstances(toxins)producedbycertainbacteriaenterthebloodstream.

pyemia:iscausedbypurulentmicroorganismsintheblood.

Section4ImmunityagainstBacterialInfectionsNon-specificimmunitySpecificimmunity

Non-specificorinnateimmunityanatomicalbarriershumoralfactorsphagocyticcells1.skinandmucosabarrier：①theintactskinandmucousmembranesofthebodyaffordahighdegreeofprotectionagainstpathogens.②secretebactericin,fattyacid,lacticacid，antibacterialpeptidelysozyme，lactoferrinetc.③normalflora2.blood-brainbarrier3.placentalbarrierAnatomicalbarriersPhagocyticcellssmallphagocyticcell---neutrophillargerphagocyticcell---MPS(mononuclearphagocytesystem)

1.Thestepsofphagocytosis:

chemotaxisrecognitionandbindingingestiondigestion(phagolysome)(phagosome)2.bactericidalmechanism：phagosomelysosomephagolysomefusedigestionoftheingestedmaterial

Oxygen-dependentmechanismreactiveoxygenintermediate—ROIO-,HO,OH-222halogenationofthebacterialcellwallhydrogenperoxide

halideionsmyeloperoxidaseconvertingaminoacidintoaldehydesNitrogen-dependentmechanismenzyme:NOsynthaseOxygen-independentmechanismenzyme:lysozyme;defensins;hydrolaseTNFpH:3.5-4.03.ResultsofPhagocytosis

completephagocytose：Thelysosomesfusewiththephagosomescontainingtheingestedmicrobesandthemicrobesaredestroyed.un-completephagocytose:Somebacteria,suchasLegionellapneumophilaandMycobacteriumspecies,aremoreresistanttophagocyticdestructiononceengulfed.tissuedamage：hydrolase→inflammationhumoralfactors1．complementC5b6789;C3b,C4b;C3a,C5a2．cytokinesIL-1,IL-6,TNF-α3．a(chǎn)cute-phaseproteinC-reactionprotein

Acquiredimmunityhumoralimmunitycell-mediatedimmunityIgEIgGIgDIgMIgAperforingranzymeIFN-

IL-2、TNF-

MucosaimmunityCD4+Th1CD8+CTLSIgAanti-extracellularbacteriaSkinandmucosabarrierphagocyticcells:neutrophil(PMN),macrophage,monocytes

complementantibodycellmediatedimmuneresponseCD4+Th2Anti-intracelllularbac