医学免疫学英文版课件：introduction

IntroductionandHistoryofImmunologyWeilinChen,Ph.DInstituteofimmunology,ZJUEmail:cwl@/0099231

Lecture1HistoryofImmunologyImmunesystemInnateimmunityAdaptiveimmunity

Textbook:MedicalImmunology6thed（曹雪涛）References:NaturalReviewofImmunologyAnnualReviewofImmunologyImmunityImmunity:referstoallmechanismsusedbythebodyasprotectionagainstenvironmentalagentsthatareforeigntothebody.Theterm“immunity”wasfirstusedin1775byVanSweiten,aDutchphysician,as“immunitas”todescribetheeffectsinducedbyanearlyattemptatvariolization.Variolization

•ToinduceimmunitydeliberatelywereperformedbytheChineseinthe1200–atechniquecalledvariolization•EdwardJenneranEnglishcountrydoctorin1798,tookthescrabfromSarahNelmes,amilkmaidsandinsertedintoarmofJamesPhipps,a8-yearoldboy.Eightweekslater,Jameswaschallengedwiththedeadlysmallpox.

LouisPasteur(1822-1895)

Pasteurcalledtheattenuatedstrainas“Vaccine”.Thelatinword“vacca=cow”inhonorofJenner’swork.

Attenuatedvaccinesforcholera（霍乱）,anthrax（炭疽）,andrabies（狂犬病）OnJuly4,1886,9-year-oldJosephMeisterwasbittenrepeatedlybyarabiddog，Pasteurtreatedhimwithhisattenuatedrabiesvaccinetwodayslater.Meistersurvived.JosephMeisterlaterbecomeagatekeeperforthePasteurInstitute.In1940,whenhewasorderedbytheGermanoccupierstoopenPasteur'scrypt,JosephMeisterrefusedandcommittedsuicide!

Robert

Koch(1843-1910)

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Germanphysician;alsostartedtoworkonAnthrax（炭疽）in1870's.Identifiedthesporestage.

Firsttimethecausativeagentofaninfectiousdiseasewasidentified.

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Discoveredthetuberclebacillusandtuberculin.Detailedtuberculinskintest(DTH).Awarded1905NobelPrize.

EmilAdolfvonBehring(1854–1917)

AStudentofKochWithKitasatoandWernike,discoveredanti-toxinforDiphtheria（白喉）andTetanus（破伤风）andappliedastherapy.AwardedfirstNobelPrizeinphysiology,1901

PaulEhrlich(1854–1915)

Developedaseriesoftissue-stainingdyesincludingthatfortuberclebacillus.

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WorkedwithKoch.Developedanti-toxin(Diphtheria)·

Side-chaintheoryofantibodyformation:"surfacereceptorsboundbylock&key;Agstimulatedreceptors"

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Shared1908NobelPrizewithMetchnikoff.

ElieMetchnikoff(1845-1916)

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Embryologiststudyingstarfishdevelopment.·

Foundphagocytosis.

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Birthofcellularimmunology

SharedNobelPrizewithEhrlichin1908

SirFrankMacfarlaneBurnet(1899-1985)

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Importantworkoninfluenza.Discoveryofaninfluenzaviralenzymewiththespecificityforparticularformsofneuramicacid（神经氨酸）.Usedtodayfordetection.Clonalselectiontheorytoexplaintolerance1960NobelPrizeforthediscoveryofacquiredimmunologicaltolerance.Rejectionofdonorgraftswasduetoanimmunologicalreactionandthattolerancecanbebuiltupbyinjectionsintoembryos.GeraldM.Edelman1929-RodneyR.Porter1917-19851972NobelPrizefortheirdiscoveriesconcerningthechemicalstructureofantibodies.BARUJBENACERRAFJEANDAUSSETGEORGED.SNELLDiscoveredgenesthatregulateimmuneresponses(Irgene),Nowknownadthemajorhistocompatibilityantigens1980NobleprizeNielsK.Jerne(1912-1994)

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Antibodyaviditymaturation·

Plaqueformingassay·

Pre-existingrepertoire(inhostDNA)theoryhelpedtheformationofclonalselectiontheory.·

HostMHCisthedrivingforceforthematurationandselectionofTcellsinthethymus.·

**IdiotypenetworkNobelPrize,1984,fortheoriesconcerning"thespecificityindevelopmentandcontroloftheimmunesystem"andthediscoveryof"theprincipleforproductionofmonoclonalantibodies."

Milstein(b.1927)andKöhler(1946-1995)·

Monoclonalantibody

SusumuTonegawa(b.1939)CloningoftheImmunoglobulingene1987Nobelprizeforhisdiscoveryof"thegeneticprincipleforgenerationofantibodydiversity".

PeterC.DohertyandRolfM.Zinkernagel·

Twosignals·

1996NobelPrizefortheirdiscoveriesconcerning "thespecificityofthecell-mediatedimmunedefense".

Whyweneedtostudyimmunology?NewemergingdiseasesareclosetousResurrectionof1918FluFromSequencedFragmentsHIVandAIDSAutoimmunityAllergyGraftrejection免疫系统的功能1.免疫防御（immunologicaldefense）

指机体对外来微生物及其毒素的免疫保护作用；应答过强或持续过长→超敏反应；应答过低或缺如→免疫缺陷病。2．免疫自稳(immunologicalhomeostasis)

免疫系统通过调节网络实现免疫系统功能相对稳定；自稳机制发生异常→自身免疫病。3.免疫监视（immunologicalsurveillance）

指免疫系统识别畸变和突变细胞并将其清除的功能；免疫监视功能异常→肿瘤发生或持续病毒感染。免疫刺激剂免疫系统（免疫器官、细胞、分子）免疫应答抗体致敏的淋巴细胞细胞因子补体急性期蛋白等免疫调控正常异常应用自身耐受抗感染抗肿瘤变态反应性疾病移植物排斥免疫缺陷病染自身免疫病感染肿瘤免疫学治疗免疫学预防免疫学诊断《医学免疫学》的主要研究内容：Skin&Mucousmembranesrapidlyregeneratingsurfaces,peristalticmovement,mucociliaryescalator,vomiting,flowofurine/tears,coughingCellularandhumoraldefenceslysosyme,sebaceous/mucoussecretions,stomachacid,commensalorganisms,complementproteins,phagocytosis,NKcellsCellularandhumoraldefencesAntibodies,cytokines,Thelpercells,cytotoxicTcells

ImmuneresponsesBarriersInvasion&infectionInnateimmunityAdaptiveimmunityInflammationImmuneResponses

innateimmuneresponse

naturalimmuneresponse

non-specificimmuneresponse

adaptiveimmune

response

acquiredimmuneresponse

specificimmuneresponseTheinnateandadaptiveimmuneresponseCharacteristicsCellsMolecularsInnateimmunityRespondsrapidlyNomemoryPhagocytes(PMNsandmacrophages)NaturalkillercellsMastercellsDendriticcellsPRRCytokinesComplementAcutephaseproteinsAdaptiveimmunitySlowtoostartHighlyspecificToleranceMemoryTcellsBcellsDendriticcellsAntibodiesCytokinesinnateimmuneresponse

Physiologicalbarriersskinmucousmembranes

Phagocytosispolymorphonuclearleukocytes(PMN)macrophages

Naturalkiller(NK)cell

cytokinesandinflammationMacrophageattackingbacteria(Lung)MacrophageAttackingE.coli

adaptiveimmuneresponse

Theactivationoflymphocytes

antigenTCR(Tcellreceptor)BCR(Bcellreceptor)

Proliferationanddifferentiationoflymphocytes

Bcell----cytokinesTcell----Antigen-TCR;co-stimulatorysignal

Effectivecell

Bcell----Antibody;Tcell----CTL

MemorycelladaptiveimmuneresponsePhagocyticcellsMonocytes/Macrophages

functions:1removeparticulateantigens2takeup,peocessandpresentantigenicpeptidestoTcellsdistribution:KupffercellsinthelivermicroglialcellsinthebrainadaptiveimmuneresponseImmuneResponsePhagocyticcellsmonocytePhagocyticcellsNeutrophils1.neutrophilsareshort-livedphagocyticcells

multilobednucleus;10-20μm2.neutrophilshavealargearsenalofantibioticproteingranules:lysosomes;lactoferrin;lysozymeNeutrophil

Lymphocytes1.Lymphocytesarewhollyresponsibleforthespecificimmunerecognitionofpathogens,sotheyinitiateadaptiveimmuneresponses.2.Lymphocytesarederivedfrombone-marrowstemcells.3.Blymphocytesdevelopinthebonemarrow.Tlymphocytesdevelopinthethymus.BLymphocytes⑴BCR:asurfacereceptorspecificforaparticularantigen⑵Bcellsantigenplasmacellssecreteantibody⑶humoralimmunityBLymphocytesTLymphocytes⑴TCR:T-cellantigenreceptorTCRαβ+>95%

TCRγδ+1–5%⑵CTL,cytotoxicTcellsregulatoryTcellshelperTcells,Th⑶CMI,cellmediatedimmunityAntigenpresentingcells

Macrophage:antigenprocessinghighantigenpresentinglowDentriticcell(DC):antigenpresentinghighAntigenpresentingcellsNaturalkillercells(NK)⑴15%ofbloodlymphocytes⑵expressneitherT-cellnorB-cellantigenreceptorsComponentsofbloodTissuesandorgansoftheimmunesystemPrimarylymphoidorgansthebonemarrowthethymusglandSecondarylymphoidorgansthespleenlymphnodesMucosal-associatedlymphoidtissueFunctionsoflymphoidorgans

theplaceinwhichproliferationofHSCtakeplacetheplaceinwhichdevelopmentandmaturationofBcellsoccur3.SecondaryhumoralresponseandproduceantibodiesBonemarrowThymus1.Cells:thymicstromalcells(TSC)thymocytesTcell(αβ+)monocytes,macrophage,TDC2.Structure:cortex---immaturethymocytesmadulla---maturethymocytesMø,TDC3.Function:ItisthesiteofTcellmaturation;

ItdeterminesthespecificityoftheTCRexpressedontheTcellsreleasedtoperiphery

thymusglandspleen1.adultspleen:13*8cm180-250g2.thewhitepulp:lymphoidcellstheredpulpvenoussinusescellularcords3.function:areservoivforplatelets,erythrocytesandgranulocytes;destroytheAg,agedplatelets

spleenDownloadedfrom:StudentConsult(on1June200602:08PM)©2005ElsevierlymphnodeHuman:2-10mmindiameterroundandkidneyshapedConsistsof: