免疫2_精品文档.ppt

免疫2_精品文档.ppt

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Immunity,Stateofprotectionagainstforeignorganismsorsubstances（antigens）DefenceagainstdiseaseDefenceagainsttumours,Figure1,Immuneresponsesaredirectedatourbarrierswiththeenvironment,InnateImmunity,Nonspecificimmuneresponseswhichincludeanatomic,physiologic,phagocyticandinflammatorybarriersthathelppreventtheentranceandestablishmentofinfectiousagents.Thesekeeptheinvadingpathogenatbayuntilaspecificresponsecanbemade.,AcquiredImmuneresponses,SpecificresponsemadeagainstaparticularpathogenoragentDiverse-responsescanpotentiallybemadeagainstanypathogenetc.Memory-theimmunesystemcanrememberapathogenthathaspreviouslyinfectedthebodyEscalatingresponse-andgeneratesafastermoreeffectiveresponsenexttime!

Howisthisachieved?

2inter-relatedevents:

recognitionofantigenresponsetoantigen,Figure2,Theimmunesystemiscompartmentalisedtoenablelymphocytestocomeintocontactwithpathogens/antigens.,AntigenPresentation,Antigenpresentingcells（dendriticcells,macrophages）,BlymphocytesandTlymphocytesareinvolvedinthegenerationofimmuneresponses.BothBandTlymphocytespossessantigenreceptorsintheircellmembrane.,Blymphocytereceptors（BCR）,AntibodymoleculesboundtothecellmembraneformtheBcellreceptor（BCR）BCRcanrecogniseandinternaliseintactantigen.（antigenherecanbea3-dimensionalstructure）,Figures3and4,StructureoftheBcellreceptor,Tlymphocytereceptors（TCR）,TlymphocytesonlyrecogniseantigenassociatedwithMHCclassIandclassIImoleculesantigenhereisashortlinearpeptide-primarystructure,Figures5,6and7,StructureoftheTCRanditsinteractionwithMHC/peptidecomplexes,HowareimmuneresponsesDIVERSE?

EachTandBlymphocytehasaDIFFERENTantigenreceptorClonalexpansionofasinglecellresultswhenthelymphocytereceptormeetsitsspecificantigen.Expandedlymphocytesthendevelopdifferenteffectorandmemoryfunctions,FunctionofTlymphocytesI,Thereare2majorsub-populations.HelperTcells（Th）andcytotoxicTcells（Tc）.ThcellsexpressCD4andrecogniseantigen+classIIMHC（onantigenpresentingcells）.Antigenisapeptideof18-22aminoacids,andisderivedfromproteinsfromoutsidethecell.fightextracellularpathogens.（canproducesolublemediators=cytokines.）,HelperCD4Tlymphocytes,FunctionsofTlymphocytesII,TccellsexpressCD8andrecogniseantigen+classIMHC（onallbodycells）.Antigenisapeptideof9aminoacids,andisderivedfromproteinssynthesisedinsidethecell.NormallyselfpeptidesareexpressedinclassIMHC.fightintracellularpathogens.（canlysebodycells!

）,CytotoxicCD8Tlymphocytes,FunctionsofBlymphocytes,Bcellantigenreceptor-membraneboundantibodymoleculeActivatedBcellsbecomeplasmacellsandsecreteantibody-potentsolubleeffectormolecues（IgM,IgG,IgA,IgE,IgD）NeedTcellhelptobecomeactivatedExpressclassIIMHCandcanactivateCD4+Tcells,FunctionsofBlymphocytes,Wheredoimmuneresponsetakeplace?

Specificlymphocytesneedtocomeintocontactwithspecificpathogen/antigentomakeanimmuneresponseThisoccursinthespecialisedmicro-environmentofthelymphnodeFigure8.Structureofalymphnode,Wheredopathogensenterthebody?

Barriers-skin,nasopharynx,gut,lungs（mucosa）a）recognisepathogenb）makeanimmuneresponseThemucosacontainsorganisedlymphoidtissue（egpeyerspatchesinthegut）andmanylymphocytes,Classexercise,WhathappensifIvaccinateyou?

WhydoIdothis?

Howdoesitwork?

WhyisiteffectiveWhathappenswhenyoueatfood?

Whathappenstofood?

Wheredoesitgo?

Doyoumakeanimmuneresponsetofood?

Whymightyouhaverheumatoidarthritisormultiplesclerosiswhatarethesymptoms?

whatishappening?

whatisthecause?

Sowhydontyourespondtoselfantigen?

Tolerance,TandBlymphocyteshaveuniqueantigenreceptorsTheTcellreceptor（TCR）isproducedbythegeneticorganisationgerm-lineDNAThereareapproximately1017differentTCRs!

Duringdevelopment,TCRsgothrough2selectionprocedures,Thymiceducation,Pre-Tcellintothethymus:

Positiveselection:

TCRbindstoMHC=GROWNegativeselection:

TCRhashighaffinityforMHC+selfpeptide=DIEmatureTcell,Figure9,Structureandfunctionofthethymus,WhathappensifIvaccinateyou?

Intentionaladministrationofaharmlessorlessharmfulformofapathogentoinduceaspecificimmuneresponsethatprotectstheindividualagainstlaterexposuretothesamepathogen.Stimulatespecificadaptiveimmuneresponse（antibodies;Tcells）Memory,Figures10,11and12,Vaccinationprotocols,effectondiseaseprevalenceandimmuneresponse,Whathappenswhenyoueatfood?

IngestkilogramquantitiesofforeignantigenDigestandabsorbnutrientsetcDonotmakeanimmuneresponseagainstfood（exceptindiseaseeg）coeliacdisease-respondtoglutenThemucosalimmunesystemfunctionstoswitchoffresponsestoingested/inhaledantigens.,THISISORALTOLERANCE,Whymigh