免疫學(xué)發(fā)展史

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

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

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

第6頁/共25頁7ImmunisationagainstSmallpox

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

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

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

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

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

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

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

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

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

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