免疫學(xué)發(fā)展史

免疫學(xué)發(fā)展史第1頁(yè)/共25頁(yè)2StagesofImmunologyDescriptiveearlyperiodEarlyattemptsatvaccination:SmallpoxEarlyexperiments:BacteriacausediseaseHumoralv.cellularimmunitySelectivev.instructivetheoriesofI.R.Themolecularrevolutionpresent第2頁(yè)/共25頁(yè)3DescriptiveEarlyPeriodPlagues&pandemics,esp.bubonicplague(Pasteurellapestis)&smallpox.Causesofdiseaseunknownuntil19thC.Thoughttobecausedbypoisons=“virus”(latin).

Thucydides(5thC.B.C.):peoplewhorecovered-immune第3頁(yè)/共25頁(yè)4EarlyAttemptsatImmunisationMithradatesVI(AnatolianKing)tookincreasingdailydosesofpoisons.ImmunisationagainstSmallpox:-Chinese:driedmatterfrompustulesinsertedinnostrils.Turks:usedvariolation,henceVariolaVirus.第4頁(yè)/共25頁(yè)5ASmallpoxVictim第5頁(yè)/共25頁(yè)6ImmunisationagainstSmallpox

(1) VariolationEarly18thC.:LadyMaryWortleyMontagu(wifeofBritishAmbassador,Constantinople)inoculatedownchildren.“TheRoyalExperiment” GeorgeIpardoned7criminals:inoculated;1laywithsmallpoxvictimeverynighttoend.Allrecovered.Repeatedwith6morecriminals+5orphans. Then2daughtersofPrince&PrincessofWalesinoculated,hencebecamepopular.

第6頁(yè)/共25頁(yè)7ImmunisationagainstSmallpox

(2) VaccinationEndof18thC.:EdwardJennerInoculated7subjectswithcowpox.2challengedwithsmallpox.AllO.K.

Cowpox=Vacciniavirus,hencevaccinationgeneralterm.第7頁(yè)/共25頁(yè)8EdwardJennerinoculatingJamesPhippswithcowpox第8頁(yè)/共25頁(yè)9第9頁(yè)/共25頁(yè)10ImmunisationagainstSmallpox(3)WHOProgramme1978:WHOProgrammecompleted.Smallpoxcompletelyeradicatedworldwide.第10頁(yè)/共25頁(yè)1119thC.:BacteriacausediseaseRobertKoch&LouisPasteurestablishedbacteriaascauseofdiseases.Pasteur:Injectedanimalswithliveattenuatedmicoorganismsimmunityv.chickencholera,anthrax,rabies.

第11頁(yè)/共25頁(yè)12WarsofTheCellsandAntibodiesCellularTheory:ElieMetchnikoff Phagocytesinstarfishlarvaesurroundasplinter;phagocytosis&digestionofbacteriabyMs&polymorphs

PhagocyticTheory(innateimmunity).G.B.Shaw,“TheDoctor’sDilemma”:“….stimulatethephagocytes”.HumoralTheory:

Koch,Ehrlichetal.(Berlin)Showedserumfromimmunisedanimalskillsbacteria.第12頁(yè)/共25頁(yè)13IlyaMetchnikoff第13頁(yè)/共25頁(yè)14HumoralImmunityBordetdiscoveredcomplement.Behring&Kitasato–immunitytodiphtheria&tetanusduetoAbs.v.toxins.Passivetf.ofimmuneserumprotection=1stimmunotherapy.

第14頁(yè)/共25頁(yè)15第15頁(yè)/共25頁(yè)16WarsofTheCellsandAntibodies:TruceSirAlmothWright&Douglas-OpsonisationofbacteriabyAbs.AttemptedfusionofCellularandHumoralTheories–“SirAlmostRight”.Littleprogressincellularimmunologyfor50years(unfashionable).

第16頁(yè)/共25頁(yè)1720thC:HowareAbs.made?Selectivev.InstructiveTheoriesAreAbspre-made(selective)or“moulded”byag(instructive)?Ehrlich’sSideChainTheory(selective)Pauling-InstructiveTheory

SirMacFarlaneBurnet–ClonalSelectionTheory.第17頁(yè)/共25頁(yè)18第18頁(yè)/共25頁(yè)19ChemicalapproachtoAbs.&Ags.Landsteiner:Specificity&diversity;bloodgroupags.AbsasproteinsPorter&Edelman:1stDescriptionofstructureofIgG第19頁(yè)/共25頁(yè)20R.R.Porter第20頁(yè)/共25頁(yè)21ReturntoCellularTheories(InparallelwithstudiesofAbs.)Humoralimmunitycannotexplaingraftrejection,tolerance,immunitytoviruses.

Medawar–tolerancetoskinallograftsRoleofT-cells:Thcells(T-Bcellcooperation),Tccells(killvirusinfectedcells).Zinkernagel&Doherty–Tcrecogniseag.boundtoMHC第21頁(yè)/共25頁(yè)221975–present:TheMolecularRevolution(1)K?hler&Milstein:MonoclonalAbsNobelPrize1984第22頁(yè)/共25頁(yè)231975–present:TheMolecularRevolution(2)Tonegawa–geneticbasisofAbvariabilityPCR&genecloningtechniques+Mabs.identification,structure&functionofIg&TCRgenes,cellsurfaceags.&cytokines.

第23頁(yè)/共25頁(yè)241975–present:TheMolecularRevolution(3)Geneticmanipulation:GeneK.O.andtransgenicmice