Introduction and History of Immunology Weilin Chen, Ph.D Institute of immunology, ZJUPhone:88208282Email: Lecture 1 History of Immunology Immune system Innate immunity Adaptive immunity Text book:Medical Immunology 5th ed（金伯泉）References:Natural Review of ImmunologyAnnual Review of ImmunologyImmunityImmunity: refers to all mechanisms used by the body as protection against environmental agents that are foreign to the body.The term “immunity” was first used in 1775 by Van Sweiten, a Dutch physician, as “immunitas” to describe the effects induced by an early attempt at variolization.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,1901PaulEhrlich(18541915)Developedaseriesoftissue-stainingdyesincludingthatfortuberclebacillus.WorkedwithKoch.Developedanti-toxin(Diphtheria)andhemalysisSide-chaintheoryofantibodyformation:surfacereceptorsboundbylock&key;AgstimulatedreceptorsShared1908NobelPrizewithMetchnikoff.ElieMetchnikoff(1845-1916)Embryologiststudyingstarfishdevelopment.Foundphagocytosis.Phagocytesfromlarvastuckonthornfromatangerinetree.LaterhefoundafungalsporeattachedtoaphagocyteofDaphnia.Formedthebasisofleukocytephagocytosis.BirthofcellularimmunologySharedNobelPrizewithEhrlichin1908SirFrankMacfarlaneBurnet(1899-1985)Importantworkoninfluenza.Discoveryofaninfluenzaviralenzymewiththespecificityforparticularformsofneuramicacid.Usedtodayfordetection.Clonalselectiontheorytoexplaintolerance1960NobelPrizeforthediscoveryofacquiredimmunologicaltolerance.Rejectionofdonorgraftswasduetoanimmunologicalreactionandthattolerancecanbebuiltupbyinjectionsintoembryos.GeraldM.Edelman1929-RodneyR.Porter1917-19851972NobelPrizefortheirdiscoveriesconcerningthechemicalstructureofantibodies.BARUJBENACERRAFJEANDAUSSETGEORGED.SNELLDiscoveredgenesthatregulateimmuneresponses(Irgene),Nowknownadthemajorhistocompatibilityantigens1980NobleprizeNielsK.Jerne(1912-1994)AntibodyaviditymaturationPlaqueformingassayPre-existingrepertoire(inhostDNA)theoryhelpedtheformationofclonalselectiontheory.HostMHCisthedrivingforceforthematurationandselectionofTcellsinthethymus.*IdiotypenetworkNobelPrize,1984,fortheoriesconcerningthespecificityindevelopmentandcontroloftheimmunesystemandthediscoveryoftheprincipleforproductionofmonoclonalantibodies.Milstein(b.1927)andKhler(1946-1995)MonoclonalantibodySusumuTonegawa(b.1939)CloningoftheImmunoglobulingene1987Nobelprizeforhisdiscoveryofthegeneticprincipleforgenerationofantibodydiversity.PeterC.DohertyandRolfM.ZinkernagelTwosignals1996NobelPrizefortheirdiscoveriesconcerningthespecificityofthecell-mediatedimmunedefense.Why we need to study immunology?New emerging diseases are close to usResurrection of 1918 Flu From Sequenced FragmentsHIV and AIDSAutoimmunityAllergyGraftrejectionSkin&Mucousmembranesrapidly regenerating surfaces, peristalticmovement, mucociliary escalator,vomiting, flow of urine/tears, coughingCellularandhumoraldefenceslysosyme, sebaceous/mucous secretions,stomach acid, commensalorganisms,complement proteins,phagocytosis, NK cellsCellularandhumoraldefencesAntibodies, cytokines, T helper cells,cytotoxic T cellsImmuneresponsesBarriersInvasion&infectionInnateimmunityAdaptiveimmunityInflammationImmune Responses innate immune response natural immune response non-specific immune response adaptive immune response acquired immune response specific immune responseThe innate and adaptive immune responseCharacteristicsCellsMolecularsInnateimmunityRespondsrapidlyNomemoryPhagocytes(PMNsandmacrophages)NaturalkillercellsMastercellsDendriticcellsCytokinesComplementAcutephaseproteinsAdaptiveimmunitySlowtoostartHighlyspecificMemoryTcellsBcellsDendriticcellsAntibodiesCytokinesinnate immune response Physiological barriers skin mucous membranes Phagocytosis polymorphonuclear leukocytes(PMN) macrophages Natural killer(NK) cell cytokines and inflammationMacrophage attacking bacteria(Lung) Macrophage Attacking E. coli adaptive immune response The activation of lymphocytes antigen TCR(T cell receptor) BCR(B cell receptor) Proliferation and differentiation of lymphocytes B cell-cytokines T cell-Antigen-TCR;co-stimulatory signal Effective cell B cell-Antibody; T cell-CTL Memory celladaptive immune responseadaptive immune