《遗传学概论》PPT课件

IntroductionandHistoryofImmunology,Instituteofimmunology,ZJU,Lecture1,HistoryofImmunologyImmunesystemInnateimmunityAdaptiveimmunity,Textbook:MedicalImmunology5thed（金伯泉）References:NaturalReviewofImmunologyAnnualReviewofImmunology,Immunity,Immunity:referstoallmechanismsusedbythebodyasprotectionagainstenvironmentalagentsthatareforeigntothebody.Theterm“immunity”wasfirstusedin1775byVanSweiten,aDutchphysician,as“immunitas”todescribetheeffectsinducedbyanearlyattemptatvariolization.,Variolation,ToinduceimmunitydeliberatelywereperformedbytheChineseinthe1200atechniquecalledvariolationEdwardJenneranEnglishcountrydoctorin1798,tookthescrabfromSarahNelmes,amilkmaidsandinsertedintoarmofJamesPhipps,a8-yearoldboy.Eightweekslater,Jameswaschallengedwiththedeadlysmallpox.,LouisPasteur(1822-1895)Pasteurcalledtheattenuatedstrainas“Vaccine”.Thelatinword“vacca=cow”inhonorofJennerswork.Attenuatedvaccinesforcholera,anthrax,andrabiesOnJuly4,1886,9-year-oldJosephMeisterwasbittenrepeatedlybyarabiddog，Pasteurtreatedhimwithhisattenuatedrabiesvaccinetwodayslater.Meistersurvived.JosephMeisterlaterbecomeagatekeeperforthePasteurInstitute.In1940,whenhewasorderedbytheGermanoccupierstoopenPasteurscrypt,JosephMeisterrefusedandcommittedsuicide!,RobertKoch(1843-1910)Germanphysician;alsostartedtoworkonAnthraxin1870s.Identifiedthesporestage.Firsttimethecausativeagentofaninfectiousdiseasewasidentified.Discoveredthetuberclebacillusandtuberculin.Detailedtuberculinskintest(DTH).Awarded1905NobelPrize.,EmilAdolfvonBehring(18541917)AStudentofKochWithKitasatoandWernike,discoveredanti-toxinforDiphtheriaandTetanusandappliedastherapy.AwardedfirstNobelPrizeinphysiology,1901,PaulEhrlich(18541915)Developedaseriesoftissue-stainingdyesincludingthatfortuberclebacillus.WorkedwithKoch.Developedanti-toxin(Diphtheria)andhemalysisSide-chaintheoryofantibodyformation:surfacereceptorsboundbylockAgstimulatedreceptorsShared1908NobelPrizewithMetchnikoff.,ElieMetchnikoff(1845-1916)Embryologiststudyingstarfishdevelopment.Foundphagocytosis.Phagocytesfromlarvastuckonthornfromatangerinetree.LaterhefoundafungalsporeattachedtoaphagocyteofDaphnia.Formedthebasisofleukocytephagocytosis.BirthofcellularimmunologySharedNobelPrizewithEhrlichin1908,SirFrankMacfarlaneBurnet(1899-1985)Importantworkoninfluenza.Discoveryofaninfluenzaviralenzymewiththespecificityforparticularformsofneuramicacid.Usedtodayfordetection.Clonalselectiontheorytoexplaintolerance1960NobelPrizeforthediscoveryofacquiredimmunologicaltolerance.Rejectionofdonorgraftswasduetoanimmunologicalreactionandthattolerancecanbebuiltupbyinjectionsintoembryos.,GeraldM.Edelman1929-,RodneyR.Porter1917-1985,1972NobelPrizefortheirdiscoveriesconcerningthechemicalstructureofantibodies.,BARUJBENACERRAF,JEANDAUSSET,GEORGED.SNELL,Discoveredgenesthatregulateimmuneresponses(Irgene),Nowknownadthemajorhistocompatibilityantigens1980Nobleprize,NielsK.Jerne(1912-1994)AntibodyaviditymaturationPlaqueformingassayPre-existingrepertoire(inhostDNA)theoryhelpedtheformationofclonalselectiontheory.HostMHCisthedrivingforceforthematurationandselectionofTcellsinthethymus.*IdiotypenetworkNobelPrize,1984,fortheoriesconcerningthespecificityindevelopmentandcontroloftheimmunesystemandthediscoveryoftheprincipleforproductionofmonoclonalantibodies.,Milstein(b.1927)andKhler(1946-1995)Monoclonalantibody,SusumuTonegawa(b.1939)CloningoftheImmunoglobulingene1987Nobelprizeforhisdiscoveryofthegeneticprincipleforgenerationofantibodydiversity.,PeterC.DohertyandRolfM.ZinkernagelTwosignals1996NobelPrizefortheirdiscoveriesconcerningthespecificityofthecell-mediatedimmunedefense.,Whyweneedtostudyimmunology?,Newemergingdiseasesareclosetous,Resurrectionof1918FluFromSequencedFragments,HIVandAIDS,Autoimmunity,Allergy,Graftrejection,Skinco-stimulatorysignalEffectivecellBcell-Antibody;Tcell-CTLMemorycell,adaptiveimmuneresponse,adaptiveimmuneresponse,ImmuneResponse,Phagocyticcells,Monocytes/Macrophagesfunctions:1removeparticulateantigens2takeup,processandpresentantigenicpeptidestoTcellsdistribution:Kupffercellsinthelivermicroglialcellsinthebrain,Phagocyticcells,monocyte,Phagocyticcells,Neutrophils1.neutrophilsareshort-livedphagocyticcellsmultilobednucleus;10-20m2.neutrophilshavealargearsenal（军火库，兵工厂）ofantibioticproteingranules:lysosomes;lactoferrin;lysozyme,Neutrophil,Lymphocytes,1.Lymphocytesarewholly完全的responsibleforthespecificimmunerecognitionofpathogens,sotheyinitiateadaptiveimmuneresponses.2.Lymphocytesarederivedfrombone-marrowstemcells.3.Blymphocytesdevelopinthebonemarrow.Tlymphocytesdevelopinthethymus.,BLymphocytes,BCR:asurfacereceptorspecificforaparticularantigenBcellsantigenplasmacellssecreteantibodyhumoralimmunity,BLymphocytes,TLymphocytes,TCR:T-cellantigenreceptorTCR+95%TCR+15%CTL,cytotoxicTcellsregulatoryTcellshelperTcells,ThCMI,cellmediatedimmunity,Antigenpresentingcells,Macrophage:antigenprocessinghighantigenpresentinglowDentriticcell(DC):antigenpresentinghigh,Antigenpresentingcells,Naturalkillercells(NK),15%ofbloodlymphocytesexpressneitherT-cellnorB-cellantigenreceptors,Componentsofblood,Tissuesandorgansoftheimmunesystem,PrimarylymphoidorgansthebonemarrowthethymusglandSecondarylymphoidorgansthespleenlymphnodesMucosal-associatedlymphoidtissue,Functionsoflymphoidorgans,theplaceinwhichproliferationofHSCtakeplacetheplaceinwhichdevelopmentandmaturationofBcellsoccur3.ThelymphoidprogenitorcellsaretransportedbycirculatingbloodtothethymusanddifferentiateintofuctionalTlymphocytes,Bonemarrow,Thymus,1.Cells:thymicstromalcells(TSC)thymocytesTcell(+)monocytes,macrophage,TDC2.Structure:cortex-immaturethymocytesmadulla-maturethymocytesM,TDC3.Function:ItisthesiteofTcellmaturation;ItdeterminesthespecificityoftheTCRexpressedontheTcellsreleasedtoperiphery,thymusgland,spleen,1.adultspleen:13*8cm180-250g2.thewhitepulp:lymphoidcellstheredpulpvenoussinusescellularcords3.function:areservoivforplatelets,erythrocytesandgranulocytes;destroytheAg,agedplatelets,spleen,Downloa