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MicrobialPathogenesis

andHost-ParasiteRelationshipsBIOL533Lecture1MedicalMicrobiologyBIOL5331DefinitionsMicrobialpathogenesis—processofcausingdiseaseColonization—presenceofmicrobesatsiteofbodyDoesnotimplytissuedamageordiseasesymptomsDoesimplyinvasionofsiteandmultiplicationBIOL5332CharacteristicsofParasitismEncounter:agentmeetshostEntry:agententershostSpread:agentspreadsMultiplication:agentmultipliesDamage:agent,hostresponse,orbothcausedamageOutcome:agentorhostwins,orcoexistBIOL5333EncounterInuteroDonotnormallycomeincontactwithorganismsProtectionoffetalmembranesDonotnormallycomeincontactwithorganismsfrommotherNormallyonlypresentsporadicallyExceptions:sexualdiseases,viruscauses,rubellaBIOL5334EncounterChallengebetweenmanandmicrobewagesmanytimesduringlifetimeMostdisappearrapidlySomebecomepartofnormalfloraOnlyafewcausediseaseBIOL5336LaterEncountersExogenous:encounteredinenvironmentEndogenous:encounteredinoronbodyOrganismspresentonskincancausediseasewhentheygointodeepertissuesBIOL5337LaterEncountersExample:StaphylococcusaureusenterscutandformsboilInthiscase,encountertookplacelongbeforedisease(attimeskinwascolonized)EncounterisnotalwayssharplydemarcatedBIOL5338NormalFloraWhatconstitutesnormalflora?SomepeoplepossessStreptococcuspyogenesintheirthroatforlongperiods,butrarelycontractdiseaseOpportunisticpathogenexistence(carrierstate)95%ofpeopleneverhavethisbacterium,andwhentheydo,theygetsickBIOL5339NormalFloraDefinedConstitutesnormalfloraifdefinitionis“anyorganismpresentthatisnotcausingdisease”NotnormalfloraifusedtomeanorganismspresentinmajorityofpopulationBIOL53310Host-ParasiteInteractionExposuretovirulentagentsdoesnotalwaysleadtodiseaseTyphusandBlackPlagueepidemics: onlyhalfofpopulationbecamesick,eventhoughmostlikelyexposedBIOL53311Host-ParasiteInteractionResponseofparticularmicrobetoparticularhostDependsonfactorsuniquetoeachinteractionWithinasingleindividualChangeswith:AgeNutritionalstateOtherfactorsBIOL53312EntryMuchofinsideofbodyisconnectedtotheoutside;forexample:LumenofintestineAlveolioflungTubulesofkidneyAlmostallorganswithinthoraxandabdomenaretopologicallyconnectedtotheoutsideBIOL53313EntryMechanismstokeepoutinvadersSphinctersandvalvesWithexceptionofdigestiveandgenitourinarysystems,thesesitesarenormallysterileOrganismthatresidesonlumensideofintestineorlungalveolihasnotpenetratedbodyBIOL53314EntryDefinedIngressofmicrobesintobodycavitiescontiguouswithoutsideBIOL53315DigestiveSystemEnterthrougheatingNumbersoforganismsarereducedonemillionormoreinstomachBacillarydysenterycanresultfromonlyafewhundredorganismsNotmanysurviveinintestinebecauseofdigestiveenzymesandstrongforceofperistalsisBIOL53316DigestiveSystemMoresurviveinileum,butneedmechanismstopreventexpulsionSurfacecomponentsserveasadhesinstoallowadherencetoepithelialcellsPiliandsurfacepolysaccharidesDiseasessuchascholeraand“traveler’sdiarrhea”arecausedwithoutpenetratingepitheliumToxinsthataffectepithelialcellsBIOL53317RespiratorySystemEnterthroughbeinginhaledAircontainingmicrobesgoesthroughairpassages(nasalturbinates,oropharynx,larynx)MicrobesreachinglowerrespiratorysystemfacepowerfulepitheliumsweepingactionColonizationrequiresadhesionmechanismsBIOL53318OtherNotermforurinaryorgenitalentryBybypassingepithelialtissue,microbescancausediseasewithoutpenetratingdeepintotissuesCholera,whoopingcough,infectionofurinarybladderBIOL53319PenetrationintoDeeperTissuesVeryfeworganismscanpenetrateunbrokenskin(wormsareanexception)Someorganismscanpenetrateepithelialtissue;forexample:S.pneumoniae,TreponemapallidumNormallyaftersomeinjurytotissue(manytimescausedbyavirus)Viruses,byreceptorsBIOL53320CarriedinbyMacrophageAlveolarmacrophagetraporganismsinlungNormallycarryupwardonciliaryepitheliumSomecases,cancarrydeeperintotissuesSomeorganismscanlive,growinmacrophage:LegionellaBordetellapertussisHIV(viavirus-ladenmacrophagefromsemen)BIOL53321PenetrationbyOtherMeansInsectbites:numerousviralandprotozoandiseasesCutsandwounds:don’tnormallyleadtodiseaseBrushingteethordefecatingvigorouslycausesminuteabrasionsofepitheliumOrganismsquicklyclearedfrombloodbyreticuloendothelialsystemBIOL53322PenetrationbyOtherMeansInjurytointernaltissuedisruptsdefensemechanismsandseriousdiseasecanresult;forexampleSubacutebacterialendocarditisDevastatingbeforeantibioticsCausedbyoralstreptococcithatbecameimplantedonheartvalvesdamagedbyrheumaticfeverBIOL53323PenetrationbyOtherMeansOrgantransplantsorbloodtransfusionsJakob-CruetzfeldtdiseasefromtransplantedcorneasCytomegalovirusfromkidneys,probablyindonorkidneyBecauseimmunosuppressivedrugsareused,virusmaybeendogenousHepatitisB,HIVtransmittedbybloodBIOL53324DiseaseCausationWhyareorganismsadaptedtovariouslocations?Temperatureoptima;athletesfootyeastcannotgrowat37°COxygenrequirementsSpecializedfactorsimportantforcausingdisease(i.e.,virulencefactors)Virulence:degreeofpathogenicityBIOL53325VirulenceFactorExamplesExotoxinsEndotoxinsCapsulesIgAproteasesAdhesins(pili)MotilityInvasivepropertiesAbilitytoacquireironSerumresistanceAbilitytosurviveinsidephagocytesBIOL53326InoculumSizeInoculumsizecandeterminewhetherorganismscausediseaseNormally,highnumberneededtocausedisease/overcomedefenses;e.g.Bathsincontaminatedhottubs(veritablecultureofbacteria—overonehundredmillionorganismsperml)BIOL53327InoculumSizeNormallyharmlessorganismscanovercomedefenses;e.g.,PeoplegetboilsalloverbodyIflargenumberoforganismsdepositedindeepertissues,infectionusuallyresultsSurgeonprepsareatoreducenumbersBIOL53328SpreadofDiseaseGeneral:spreadonlyifovercomehostdefensesSometimesprecedes,sometimesfollowsmicrobialmultiplicationPrecede:parasitecausesmalariadisseminatedbeforemultiplicationFollow:S.aureusmultiplieslocallybeforebeingdisseminatedBIOL53329SpreadofDiseaseTypes:DirectlateralpropagationtocontiguoustissuesDisseminationtodistantsitesCharacteristics:Anatomicalfactors(e.g.,earinfections)Activeparticipationbypathogens—enzymesBIOL53330Mult