Microbe Human Interaction - Wikispaces 11+2012.pdf · PDF file1 Microbe‐Human...

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Transcript of Microbe Human Interaction - Wikispaces 11+2012.pdf · PDF file1 Microbe‐Human...

  • 1

    MicrobeHumanInteractions:Contact,InfectionandDisease

    HostMicrobeRelationships Host

    Anyorganismthatharborsanotherorganismorparticle(virus,prion)

    SymbiosisAnassociationbetween2species(livingtogether)

    Mutualism Parasitism

    Commensalism

    Mutualism Bothmembersbenefitfromrelationship E.coliproduceusefulproducts(VitK)inourlargeintestine

    Parasitism Onememberbenefits,onememberisharmed

    Commensalism Onememberbenefits,onememberisnotbenefitednorharmed

    Microbesonourskinutilizeskinproducts

    Host-Microbe Relationships: Symbiosis

    E. Coli in Lg. intestines

    Giardia in intestines

    Demodex folliculorum in hair follicle

    ResidentMicroflora

    Adulthumanbodyconsistsof:

    10trillion(1013)eukaryoticcellsHumancells

    100trillion(1014)prokaryoticcellsBacteriacells

    Wehave10timesasmanyprokaryoticcellsvs.ourowncells!!Howisthispossible?

    ResidentMicroflora

    ResidentMicroflora Microbesalwayspresentonorinthebody

    TransientMicroflora Microbespresentforshorterperiodsoftime(minutestomonths)

    ResidentMicroflora

    Whichareasharbormicroflora?

    Whataresometypesofnormalmicroflora?

    Whichbodytissues,organsandfluidsareusuallymicrobefree?

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    Typesofmicrobesandtheanatomicsitestheyoccupy TheAbsenceofResident Microflora canhaveHarmfulEffects

    Enlargement of cecum

    Vitamin deficiency

    Underdeveloped immune system

    normalbiotaareunlikelytobedisplacedbyincomingmicrobes

    limitednumberofattachmentsites chemicalorphysiologicalenvironmentcreated

    byresidentbiotaishostiletoothermicrobes

    Normalbiotaisbeneficial,oratworst,commensaltothehostingoodhealthwithafunctioningimmunesystem

    ResidentMicrobialAntagonism FirstAcquiringResidentMicroflora

    Mothersbirthcanal Mothersbreastmilk Bottlefeeding People Air Surfaces

    Theonlytimethathumansaresterileiswhentheyareinthewomb(inutero)

    Contamination,InfectionandDiseaseContamination:Microbesare

    present

    Infection(Infestationlargerparasites)

    Multiplicationofmicrobes(Microbespenetratehostdefenses,entertissue

    andMULTIPLY)

    DiseaseDisturbanceinnormalhomeostasis

    Invasionofnormallysterileregionsofthebodycanresultininfectionanddisease.

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    Factorsthatweakenhostdefensesandincreasesusceptibilitytoinfection

    oldageandextremeyouth(infancy, prematurity) geneticdefectsinimmunityandacquireddefectsin

    immunity(AIDS) surgeryandorgantransplants underlyingdisease:cancer,livermalfunction,diabetes chemotherapy/immunosuppressivedrugs physicalandmentalstress pregnancy otherinfections

    Truevs.OpportunisticPathogenTruepathogen Causediseaseinhealthyindividuals

    Associatedwithaspecificandrecognizabledisease

    Opportunisticpathogen Causediseaseinimmunecompromisedhost

    Gainaccess(injury)tosterileregions

    Staphylococcusaureus

    Vibriocholerae

    OpportunisticmicrobesOpportunistsusuallydonotcausediseaseunlesstheopportunityarises.Conditionsthatopportunistscanflourish: Failureofthehostsnormaldefenses

    Immunocompromised populations

    Introoftheorganismintounusualbodysites E.colinormalingutbutnoturinarytract

    Disturbancesinnormalmicroflora Yeastinfectionafterantibioticuse.Why?

    Pathogens,PathogenicityandVirulence

    PathogenDiseasecausingagent

    PathogenicityTheabilitytocausedisease

    VirulenceThedegreeofpathogenicity

    Influenza

    E. coli

    TheProgressofanInfection

    Pathogenneedstobecomeestablishedbybeingsuccessfulatthefollowing:

    1. Portalsofentry2. Attachment3. Survivinghostdefenses4. Causingdisease5. Portalsofexit

    Virulenceofamicrobeisdeterminedbyitsabilityto- establishitselfinahost- causedamage

    Virulencefactor:anycharacteristicorstructureofthemicrobecontributestoitsabilitytoestablishitselfinthehostandcausedamage

    TheProgressofanInfection

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    Portalofentry:theroutethatamicrobetakestoenterthetissuesofthebodytoinitiatean infection

    Exogenous:microbeoriginatingfromasourceoutsidethebodyfromtheenvironmentoranotherpersonoranimal

    Endogenous:microbealreadyexistingonorinthebody normalbiotaorapreviouslysilentinfection

    TheProgressofanInfection:1.PortalofEntry

    TheProgressofanInfection:1.PortalsofEntry

    Themajorityofpathogenshaveadaptedtoaspecificportalofentry

    ifcertainpathogensenterthewrongportal,theywillnotbeinfectious

    inoculationofthenasalmucosawiththeinfluenzaviruswillresultininfection,butiftheviruscontactstheskin,noinfectionoccurs

    TheProgressofanInfection:1.PortalsofEntry

    Occasionally,aninfectiousagentcanenterbymorethanoneportal

    Mycobacteriumtuberculosiscanenterthroughboththerespiratoryandgastrointestinaltracts

    Streptococcus andStaphylococcus canenterthroughtheskin,urogenitaltract,andtherespiratorytract

    TheSizeoftheInoculumInfectiousdose(ID)

    - theminimumnumberofmicrobesnecessarytocauseaninfectiontoproceed

    - microorganismswithsmallerinfectiousdoseshavegreatervirulence

    - IDforrickettsiaisasinglecell- IDfortuberculosisandbeaverfeverisabout10cells- IDforgonorrheais1,000cells- IDfortyphoidfeveris10,000cells- IDforcholerais1,000,000,000cells

    TheProgressofanInfection:1.PortalsofEntry

    - gainastablefootholdonhosttissues

    - dependentonbindingbetweenspecificmoleculesonboththehostand pathogen

    - pathogenislimitedtoonlythosecells(andorganisms)towhichitcanbind

    - firmattachmentisalmostalwaysaprerequisiteforcausingdiseasesincethebodyhassomanymechanismsforflushingmicrobesfromtissues

    TheProgressofanInfection:2.Attachment/Adhesion

    Structures Capsules Piliorfimbriae

    Hooks

    TheProgressofanInfection:2.Attachment/Adhesion

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    Exampleofhowfimbriaeandcapsulesareusedtoadheretothehostcell.

    TheProgressofanInfection:2.Attachment/Adhesion

    Microbesnotestablishedasnormalbiotawilllikelyencounterthehostimmunedefenseswhenfirstentering

    Phagocytes: cellsthatengulfanddestroyhostpathogensbymeansofenzymesandantimicrobialchemicals

    TheProgressofanInfection:3.SurvivingHostDefenses

    WBC engulfing S. cerevisiae

    Antiphagocytic factors:

    - Virulencefactorsthathelppathogenstoavoidphagocytes

    - Leukocidins:killphagocytes;StreptococcusandStaphylococcus

    - Slimeorcapsule:makesitdifficultforthephagocytetoengulfthepathogen;Streptococcus pneumoniae andSalmonellatyphi

    - Somebacteriasurviveinsidethephagocyte;Legionella,Mycobacterium

    TheProgressofanInfection:3.SurvivingHostDefenses

    Humanshaveknownforcenturiesthatcopperisapotentweaponagainstinfection.Newresearchshowsthatthebacteriathatcauseseriousurinarytractinfectionsstealscopperfromimmunecellstopreventthemetalfrombeingusedagainstthem.

    NatureChemicalBiology (July8,2012)

    TheProgressofanInfection:3.SurvivingHostDefenses

    Virulencefactorsaresimplyadaptationsamicrobeusestoestablishitselfinahost

    Threewaysthatmicroorganismscausedamagetotheirhost

    A. directlythroughtheactionofenzymes

    B. directlythroughtheactionoftoxins(bothendotoxinsandexotoxins)

    C. indirectlybyinducingthehostsdefensestorespondexcessivelyorinappropriately

    TheProgressofanInfection:4.CausingDisease

    Exoenzymes- enzymessecretedbymicrobesthatbreakdownandinflict

    damageontissues- dissolvethehostsdefensebarrierstopromotethespreadof

    diseasetoothertissues

    Examplesofexoenzymes- hyaluronidase:digeststhegroundsubstance that

    cementsanimalcellstogether- coagulase:causesclottingofbloodorplasma

    TheProgressofanInfection:4.CausingDiseaseEnzymes

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    TheProgressofanInfection:4.CausingDiseaseExoenzymes

    Toxin: aspecificchemicalproductofmicrobes,plants,andsomeanimalsthatcausescellulardamageinotherorganisms

    Toxinsarenamedaccordingtotheirtarget- neurotoxinsactonthenervoussystem- enterotoxinsactontheintestines- hemotoxins lyseredbloodcells- nephrotoxins damagethekidneys

    Twotypesoftoxinsinpathogenicbacteria Exotoxin Endotoxin

    TheProgressofanInfection:4.CausingDiseaseToxins

    Exotoxins- proteinsthattargetsaspecific

    celltype

    - affectcellsbydamagingthecellmembraneandinitiatinglysis

    Hemolysins- disruptthemembraneofred

    bloodcellstoreleasehemoglobin

    - Ex.Streptococcuspyogenes andStaphylococcusaureus

    TheProgressofanInfection:4.CausingDiseaseExotoxins

    Endotoxin- lipopolysaccharide(LPS),partoftheoutermembraneof

    gramnegativecellwalls- Releasedwhencellsdie- hasavarietyofsystemiceffectsontissuesandorgans- causesfever,inflammation,hemorrhage,anddiarrhea

    TheProgressofanInfection:4.CausingDiseaseEndotoxins

    Someendotoxinsarepyrogenic

    TheProgressofanInfection:4.CausingDiseaseEndotoxins

    Enablespathogentospreadtootherhosts Respiratory Salivary Skin Fecal Urogenital Blood

    TheProgressofanInfection:5.PortalofExit

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    - specificavenuebywhichpathogensexit

    - shedthroughsecretion,excretion,discharge,orsloughedtissue

    - highnumberofmicrobesinthesematerialsincreasesthelikelihoodthatthepathogenwillreachotherhosts

    - portalofexitisusuallythesameastheportalofentry,butsomepathogensuseadifferentroute

    TheProgressofanInfection:5.PortalofExit

    Microbeseventuallysettleinaparticulartargetorganandcausedamageatthesite

    - hosttissuesareweakenedasaresultofthemultiplicationofthepathogen

    - pathogensobstructtubularstructuressuchasbloodvessels,lymphaticchannels,fallopiantubes,andbileducts

    - necrosis: accumulateddamageduetopathogensleadingtocellandtissuedeath

    TheProgressofanInfection:Establishment,Spread,andPathologicEffects

    TheStepsInvolvedWhenaMicrobeCausesDiseaseinaHost

    Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

    Attaching Firmly

    FimbriaeCapsulesSurface proteinsViral spikes