脊椎和无脊椎动物免疫系统.ppt

EvasionofImmunityI,Vertebrateandinvertebrateimmunesystems.,Dr.JoHamiltonParasitologyBS,Introduction.,Successfulparasiteshaveevolvedstrategiesforsurvival&developmentinbothinvertebrateandvertebratehosts.Thegoalofaparasiteistopropagatewithinthehostandbetransmittedtothenexthost.Thegoaloftheparasitisedhostistocureorlimittheinfection.Duringthenextthreelectureswewillinvestigatestrategiesusedbyparasitestoevadethehostimmuneresponse.Inthissessionwewillrevisittheimmunesystemofbothvertebratesandinvertebrates.,Objectivesandlearningoutcomes.,Bytheendofthissessionstudentsshouldbe:Familiarwithfundamentalbiologyofvertebrate&invertebrateimmunesystems.Familiarwiththeconceptofinnateandacquiredimmunityinvertebrates.Recognisethatthereisonlyinnateimmunityininvertebrates.Recognisethekeyplayersinbothvertebrateandinvertebrateimmunesystems.,Immunity.,Resistancetoinfectioniscalledimmunity.Theterm“immunity”isderivedfromtheGreekword“immunis”meaningexempt.Therearetwotypesofimmunityinvertebrates.Innateimmunitypresentfrombirth.Acquiredimmunityresultofinfectionorvaccination.Invertebratesonlypossesinnateimmunity.,Innateimmunityinvertebrates(alsoknownasnon-specificornaturalimmunity).,Characteristics:Presentfrombirth.Non-specific-actsonmanyorganismsanddoesnotshowspecificity.Doesnotbecomemoreefficientonsubsequentexposuretosameorganisms.,Innateimmunityinvertebrates.,Non-specificHostDefencesinclude:Mechanical/physicalbarriersskin,mucosalsurfaces.Preventionofstasisperistalsis,flowofurine,upwardmovementofsecretionsinbronchialtree,coughing,vomiting.,Innateimmunityinvertebrates.,Chemicaldefences-LowpHofstomachcontents,secretionoffattyacidsintheskin.Biologicaldefencecomplement,lysozyme,interferons,antimicrobialpeptides,kinins,adhesionmolecules,hormones,lactoferrin.Cellulardefence-e.g.phagocytes.,Innateimmunityinvertebrates.,Someofthekeyplayersininnateimmunitytoconsiderinmoredetailare:Complement.Opsonization.Phagocytosis&theoxidativeburst.Inflammation.,Innateimmunityinvertebratescomplement.,Complement.-complexof17proteinspresentinnormalserum.2pathwaysclassical&alternative.,Innateimmunityinvertebratesclassicalcomplementpathway.,Antigen-antibodycomplexforms,constantregionofantibodychangesshape.ActivatesC1,acquiresesteraseactivity.ActivatedC1activatesC2&C4whichactivatesC3,etc.Eventually,C8&C9activatedformingmembraneattackcomplex(MAC)-poresintargetcellmembrane-lysis.,Innateimmunityinvertebrates-alternativecomplementpathway.,Alternativepathway-C3caninteractdirectlywithcertainchemicals(teichoicacids,LPS)foundinbacterialcellwallsandactivatethealternativepathway.,Innateimmunityinvertebratesopsonization.,Opsonization-processofcoatingmicro-organismswithplasmaproteinstomakethemmoreeasilyphagocytosable.Itisstimulatedbycomplementboundtoantibody-antigentargets.Opsonizationpromotesadhesionbetweenopsonizedcell¯ophages.Theopsoninbindstoreceptorsonphagocytemembrane.Opsonizationandphagocytosisaremoreefficientinimmuneindividuals.,Innateimmunityinvertebratescellulardefence.,Cellulardefenceinvolves:Granulocytes(alsoknownasthepolymorphonuclearleukocytese.g.eosinophils,basophilsetc).Thereticuloendothelialsystem(e.g.macrophages,Kupffercellsoftheliverandnaturalkiller(NKcells).,InnateimmunityinvertebratesWhitebloodcells.,Roleofwhitebloodcellsincellulardefence.Whitebloodcells(WBCs)aremajorcomponentsofimmunesystem.,Bloodsmearshowingdifferentbloodcelltypes.,Innateimmunityinvertebratesphagocytosis.,CertainWBCshighlymobile&carryoutphagocytosis.WBCschemotacticallyattractedtofociofdiseaseortissuedamage.Phagocytosisbeginswithengulfmentofparticulatematter(e.g.bacteria,clumpsofvirions,celldebris,etc.)intoaphagosome.,Innateimmunityinvertebratesphagocytosiscontd.,Thephagosomefuseswithlysosomestoformthephagolysosome.Lysosomescontainnumberofenzymesincludingacidhydrolases,lysozyme,neutralproteases,myeloperoxidase,lactoferrin,&phospholipaseA.Theseenzymescandegradebiomolecules.,HumanmacrophageengulfingthefungusCandidaalbicans.,Innateimmunityinvertebratesoxidativeburst.,Onceengulfed,thewhitecellmustkilltheorganismsbysomemeanssuchasthe“respiratory(oroxidative)burst.Manypathogensandparasitessucceedbecausetheyareabletoavoidphagocytosis.,Innateimmunityinvertebratesinflammation.,Inflammation-(orinflammatoryresponse)mechanismbywhichphagocytesandcomplementarerecruitedtositeoftissueinvasion.Non-specificreactiontotissuedamage.Celldamageinitiatesacomplexseriesofstepsleadingtoinflammation.,Innateimmunityinvertebratesinflammation.,Inflammationinvolves:Vasodilation-swelling.adhesionofleukocytestoendothelialcellsofpost-capillaryvenule,&emigrationofphagocytesintotissues.redness(bloodflow).pain(prostaglandinsbindtonervereceptors).heat(pyrogens).Inflammationlocalisedtoareaofinfection/injurybyreleaseofsubstancesfrommicro-organismsorchemicalmediatorsreleasedfromcellsintissues,e.g.histaminefrommastcells.Onceorganismsaredestroyedinflammationsettlesdown(resolves).,Acquiredimmunity(onlyinvertebrates).,Alsoknownasadaptiveimmunity/specificimmunity.Developsasresponsetoaninfection.Calledadaptiveasimmunesystemadaptsitselftopreviouslyunseenmolecules.Theinductionofimmunitybyinfection,orwithavaccine,iscalledactiveimmunity.,Acquiredimmunity.,Inductionofimmunitybyinfection,orwithvaccine,calledactiveimmunity.Non-immuneindividualcanbemadeimmunebytransferringserumorlymphocytesfromimmuneindividual.Thisisknowaspassiveimmunityanddemonstratesthatserumconstituents(antibodies)andlymphocytesareinvolvedinimmunity.,Acquiredimmunity.,Characteristicsofacquiredimmunity:Immunologicalrecognition.Discriminationbetweenselfandnon-self.Immunologicalspecificity.Immunologicalmemory.,Acquiredimmunity.,Immunitymediatedbyimmunesystem,respondstoinfectionbymountingimmuneresponse.Animmuneresponsemust:Recogniseamicro-organismorparasiteasforeign(non-self)asdistinctfromself.Respondtothepresenceofaforeignorganismbyproductionofspecificantibodiesandspecificlymphocytes.Mediatetheeliminationofsuchorganisms.,Acquiredimmunity.,Therearetwotypesofacquiredimmunity.Cell-mediatedimmunity-thisisimmunitymediatedbyT-cells.Tcellssecretelymphokines(erleukin-2)whichinteractwithothercelltypes,andeitheractivateorrepressanimmuneresponse.Humoralimmunity-thisisblood-specificimmunitymediatedbyantibodies(Abs).,Acquiredimmunitycellmediatedimmunity.,Acquiredimmunitycellmediatedimmunity.,Keycellsinvolvedinacquiredimmunityresponsearelymphocytes.Twotypeslymphocytedevelopinbonemarrowfromcommonprecursor.Eachdifferentresponsemediatedbydifferentsetsoflymphocytes.Followinginvasionbyaforeignorganism,lymphocytesproliferate(i.e.divide)anddifferentiate(i.e.specialize).,Acquiredimmunitycellmediatedimmunity,Blymphocytes.,Blymphocytes(Bcells):Foundfixedinthelymphnodes,liverandspleen.Theyarebonemarrow-derivedlymphocytes,matureinPeyersPatchesofthepancreas.Duringmaturation,antigen-specifiedantibodyisdisplayedonthecellsurface.Ifthecellisactivatedbyanantigen,theBcellsexcreteantibody.,Acquiredimmunitycellmediatedimmunity,Tlymphocytes.,Tlymphocytes(T-cells):Foundinlymphnodes,liver,spleen,alsofreelycirculatingintheblood.Maturesinthymus.Theyhavecellsurfacereceptorofapre-determinedspecificity.Thesecellsregulatecellularimmunity.TwomainTcelltypes:helperTcells(ThcellshavetheCD4+receptor)&suppressor/cytotoxicTcells(TccellsdisplaytheCD8+receptor).,Acquiredimmunitycellmediatedimmunity,macrophages.,Athirdimportantcelltypearemacrophages.Thesecellsplayessentialroleinprocessing&presentingimmunogenstolymphocytes.Alsoimportanteffectorcells(i.e.theycarryoutdestructionofforeignmateriale.g.phagocytosis).Carryreceptorsforantibodymoleculeswhichallowsthemtoattachtoantibody-antigencomplexesbeforephagocytosingthem.,Acquiredimmunitygenerationofimmuneresponse.,Inorderforanimmuneresponsetobeactivated,anobjectmustfirstberecognisedasforeign.Animmunogenisanymoleculethatstimulatesanimmuneresponse.Ingeneral,proteinsarethebestimmunogens,followedbycarbohydratesandthennucleicacids.Lipidsareverypoor.Anantigenisanymoleculethatiscapableofgeneratinganantibodyresponse(antigen=antibodygenerating).,Acquiredimmunitygenerationofimmuneresponse.,Uponaninitialinfection,ittakesabout4-7daystogenerateanimmuneresponse.Aftersevendaysgetprimaryimmuneresponse.Initially,IgMproducedbutBcellsdifferentiatefurtherintoIgGproducingcells.Afteraboutthreeweeksprimaryimmuneresponseturnedoff.DuringthisinitialperiodAbproducingcellsandmemoryBcellsareformed.Whensameagentencounteredbyhostagain,bodyrecognisesit,stimulatesthememorycellstosecreteAbs.Thisiscalledthesecondaryimmuneresponse.Memorycanlastforfewweeksorcanlastforyears.,Acquiredimmunitygenerationofimmuneresponse.,Therearethreetypesofeffectorimmuneresponse.Humoral(blood)-antibodyresponsemediatedbyBcells®ulatedbyTcells.Cell-mediated(cellular)-delayed-typehypersensitivityandcytotoxicitymediatedbyCD4+andCD8+Tcells.Tolerance-non-specificresponsemediatedbyTcells.Healthyindividualstoleranttoowntissues,sometimesimmuneresponsefailstorecogniseselfgivingrisetoautoimmunediseasesortransplantrejectionintransplantationsurgery.,Humoralimmunityantibodies.,LargeglycoproteinsreleasedbyBcells.Antibodies(Abs)specificallyinteractwithantigens.BodycanproducemillionsofantibodyspecificitiesgeneticallyastheBcellsmature.TherearefiveclassesofAb:IgMlargest&firstAbtobemadeantibodyresponse.IgMcanmediateneutralisation,fixcomplement,agglutinateandimmobiliseantigens.IgG-thisisthemainserumAb.Thisissynthesizedduringthesecondaryimmuneresponse.AbletodoallAbmediatedfunctions.,Humoralimmunityantibodiescontd.,IgA-ismucosalantibody.SometimescalledsecretoryAbasmucosalcellssecretethemwhenmucosalpathogensbegintoestablishcolonies.IgD-isreceptorantibodyfoundonthesurfaceofimmunocompetentcells.Thisfunctionsintheafferentresponse.IgE-bindstothesurfaceofmastcellscausingdegranulationofthecellandreleaseofhistamineintocirculation.Thisabisinvolvedwithallergies.,Humoralimmunityantibodiescontd.,Absareimportantforusinfiveways.neutralisation-anAbmoleculecoversupsitesontoxicmoleculeorvirus.opsonization-thisisAb-mediatedphagocytosis.Macrophageshaveantibodyreceptorsitesonsurface,abletobindtoantigen-plementfixation-acomplicatedsystemthatreactstoantigen/antibodycomplexes(seealsocomplementnotesininnateimmunity).,Humoralimmunityantibodiescontd.,agglutination/precipitation-Abscross-linkantigensintolargecomplexesmakingthemeasiertophagocytose&destroy.immobilization-Absbindtoflagellaetc.&preventorganismsfromescapingmacrophagedeath.,CellularimmunityThandTccells.,Oftendirectedagainstintracellularparasites&cancer.InfectedcellskilledbymacrophagesunderdirectionsofCD4+Thcells.CytotoxicTcells(CD8+directed)alsoparticipatebyreleasingtoxiccomponentswhichkillthecell.Cellsinvolvedincellularimmunitymustbeabletorecogniseself,especiallyasmanyoftheirtargetsarecellsinfectedbyagentsthatarewithinthem.Thismeanskillingonesowncellsinanefforttoridtheinfection.SelfrecognitionismediatedbytheMajorHistocompatibilityComplexantigens(MHCantigens).AllourcellsdisplaytheseMHCantigensinspecificpatternsonthecellsurface.,CellularimmunityMajorHistocompatibilityComplex.,Macrophagesmustprocesstheantigen&thendisplaypiecesoftheantigenonitscellsurface.TheythenpresentthisantigentoTcells,whichrecognizetheantigenasbeingforeignaswellasrecognisingtheMHCantigens.IftheTcell“sees”bothantigenandMHCitbecomesactivated:ifit“sees”onlytheMHCantigennothinghappens.WhenmacrophagesdisplayantigenplusClassIMHCtheystimulateCD8+cells(i.e.theymakecytotoxicTcells)whentheydisplayedantigenplusClassIIMHCtheystimulateCD4+cells(i.e.helperTcells).,Invertebrateimmunesystem.,Comparisonofvertebrateitisnon-specificandhasnomemorycomponent.Vertebrateimmunesystembothinnateandacquiredcomponents.,Invertebrateimmunity.,Theinvertebrateimmunesystemiscomprisedoftwobranches:Thehumoralresponse(N.B.thisisnotantibodymediated)isconcernedwithsolublecomponentssuchasantimicrobialpeptides(AMPs),agglutinins(lectins)andmacrokines(thesearesimilartocytokines).Thecellularresponseincludesphagocytosis(haemocytes),encapsulationandnodulation.,Invertebrateimmunityhumoralresponse.,Antimicrobialpeptides.Widerangeincludingdefensins,cecropins,andropins,ceratotoxins,drosomycin&penaeidinsetc.Theiractionleadstolysisofinvadingorganisme.g.bacteria&protozoa.Macrokines.Thereisgrowingevidenceofthesecytokine-likemolecules.Haemolymphpreparationshavebeenshowntostimulatevertebrateimmuneeffectorcells(e.g.macrophages).Agglutinins(lectins).Agglutinateinvadingorganismsmakingthemeasiertophagocytose.,Invertebrateimmunitycellularresponse.,Phagocytosis-Haemocytes(amoebocytes)frontlineofinvertebratecellular.Foreign(non-self)invadersaretakenintoaphagocytoticvacuolewhereproteolyticenzymes&freeoxygen