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LectureIntroductionandHistoryofWeilinChen,Ph.DHistoryofMedicalImmunology6thed（曹雪涛）NaturalReviewofImmunologyAnnualReviewofImmunologyImmunity:referstoallmechanismsusedbythebodyasprotectionagainstenvironmentalagentsthatareforeigntothebody.Theterm“immunity”wasfirstusedin1775byVanSweiten,aDutchphysician,as“immunitas”todescribetheeffectsinducedbyanearlyattemptatvariolization.ToinduceimmunitydeliberatelywereperformedbytheChineseinthe1200–atechniquecalledvariolationanEnglishcountrydoctorin1798,tookthescrabfromSarahNelmes,amilkmaidsandinsertedintoarmofJamesPhipps,a8‐yearoldboy.Eightwiththedeadlysmallpox.Pasteurcalledtheattenuatedstrainas“Vaccine”.Thelatinword“vacca=cow”inhonorofJenner’sAttenuatedvaccinesforcholera,anthrax,andOnJuly4,1886,9-year-oldJosephMeisterwasbittenreeatedl arabiddo，Pasteurtreatedhimwithhisattenuatedrabiesvaccinetwodayslater.Meistersurvived.JosephMeisterlaterbecomeagatekeeperthePasteurInstitute.In1940,whenhewasorderedbytheGermanoccupierstoopenPasteur'scrypt,JosephMeisterrefusedandcommittedsuicide!RobertKoch(1843-Germanphysician;alsostartedtoworkonAnthrax（炭疽）in1870's.Identifiedthesorestae.Firsttimethecausativeagentofaninfectiousdiseasewasidentified.DiscoveredthetuberclebacillusandDetailedtuberculinskintestDTH.Awarded1905NobelPrize.EmilAdolfvonBehring(1854–AStudentof••appliedastherapy.•AwardedfirstNobelPrizeinphysiology,PaulPaulEhrlich(1854–Developedaseriesoftissue-stainingdyesincludingthatfortuberclebacillus.WorkedDevelopedaseriesoftissue-stainingdyesincludingthatfortuberclebacillus.Side-chaintheoryofantibody"surfacereceptorsboundbylock&key;Agstimulatedreceptors"Shared1908NobelPrizewithElieElieMetchnikoff(1845- Embryologiststudyingstarfish Embryologiststudyingstarfish SharedNobelPrizewithEhrlichinSirFrank 9- Importantworkoninfluenza.Discoveryofaninfluenzaviralenzymewiththespecificityforparticularformsofneuramicacid.Usedtodayfordetection.Clonalselectiontheorytoexplain1960NobelPrizeforthediscoveryofacquiredimmunologicaltolerance.Rejectionofdonorgraftswasduetoanimmunologicalreactionandthattolerancecanbebuiltupbyinjectionsintoembryos.1972NobelPrizefortheirdiscoveriesconcerningthechemicalstructureofGeraldGeraldM.EdelmanRodneyR.1917- JEAN GEORGED.Discoveredgenesthatregulateimmuneresponses(Irgene),Nowknownadthemajorhistocompatibilityantigens1980NobleNielsK.Jerne(1912-Pre-existingrepertoire(inhostDNA)theoryhelpedtheformationofclonalselectiontheory.HostMHCisthedrivingforceforthematurationandselectionofTcellsinthethymus.NobelPrize,1984,fortheoriesconcerning"thespecificityindevelopmentandcontroloftheimmunesystem"andthediscoveryof"theprinciple productionofmonoclonalantibodies."MonoclonalCloningCloningothe19871987rizesgeneticprincipleforgenerationof diversit".PeterC.DohertyandRolfM.1996NobelPrizefortheirdiscoveries "thespecificityofthecell-mediatedimmunedefense".WhyweneedtostudyNewemergingdiseasesareclosetoHIVand Graft免疫防御（immunological免疫自稳(immunological

Skin&Mucous& Cellularandhumoralphagocytosis,NKcellsCellularandhumoraldefencescytotoxicTcells¤innateimmuneresponsenaturalimmuneresponsenon‐specificimmuneresponse¤adaptiveimmuneresponseacquiredimmuneresponsespecificimmuneresponseTheinnateandadativeimmuneresInnatePhagocytesNoandmacrophages)NaturalkillercellsSlowtoostartTcellsBinnateimmunemucouspolymorphonuclear¤Naturalkiller(NK)¤cytokinesand¤TheactivationofTCR(TcellrecetorBCR(Bcellreceptor)B¤EffectiveBcell‐‐‐‐Antibody;T¤Memoryfunctions:1removeparticulateantigens2takeup,peocessandpresentantigenicpeptidestoTcellsdistribution:Kupffercellsinthelivermicroglialcellsinthebrainneutrophilsareshort‐livedphagocyticcellsmultilobednucleus;10‐20μmneutrophilshavealargearsenalofLymphocytesarewhollyresponsibleforthespecificimmunerecognitionofpathogens,sotheyinitiateadaptiveimmuneresponses.Lymphocytesarederivedfrombone‐marrowstemBlymphocytesdevelopinthebonemarrow.Tlymphocytesdevelopinthethymus.B⑴BCR:asurfacereceptorspecificforaparticularantigen⑵B BTantigenpresentinglowDentriticcell(DC):antigenpresentinghighTissuesandorgansofPrimarylymphoidorgansthebonemarrowthethymusglandSecondarylymphoidorgansthespleenBonetheplaceinwhichproliferationofHSCtaketheplaceinwhichdevelopmentandmaturationofBcellsoccurThelymphoidprogenitorcellsaretransportedbycirculatingbloodtothethymusanddifferentiateintofuctionalTCells:thymicstromalcells(TSC)thmoctes Tcell(αβ+)madulla‐‐‐maturethymocytesFunction:ItisthesiteofTcellmaturation;ItdeterminesthespecificityoftheTCRexpressedontheTcellsreleasedtoperipheryadult thewhitepulp:lymphoidcellstheredpulp venoussinusesfunction:areservoivforplatelets,erythrocytesandgranulocytes;destroytheAg,agedplateletsDownloadedfrom:StudentConsult(on1June200602:08©2005roundandkidneyConsistsof:B‐cellcentralmedullalymphMucosal‐as