免疫学发展史HistoryVIP免费

1TheHistoryofImmunologyJr.Hons.ImmunologyB.Sc.D.I.Stott“Hewhoignoreshistoryisdoomedtorepeatit.”2StagesofImmunologyDescriptiveearlyperiodEarlyattemptsatvaccination:SmallpoxEarlyexperiments:BacteriacausediseaseHumoralv.cellularimmunitySelectivev.instructivetheoriesofI.R.Themolecularrevolutionpresent3DescriptiveEarlyPeriodPlagues&pandemics,esp.bubonicplague(Pasteurellapestis)&smallpox.Causesofdiseaseunknownuntil19thC.Thoughttobecausedbypoisons=“virus”(latin).Thucydides(5thC.B.C.):peoplewhorecovered-immune4EarlyAttemptsatImmunisationMithradatesVI(AnatolianKing)tookincreasingdailydosesofpoisons.ImmunisationagainstSmallpox:-Chinese:driedmatterfrompustulesinsertedinnostrils.Turks:usedvariolation,henceVariolaVirus.5ASmallpoxVictim6ImmunisationagainstSmallpox(1)VariolationEarly18thC.:LadyMaryWortleyMontagu(wifeofBritishAmbassador,Constantinople)inoculatedownchildren.“TheRoyalExperiment”GeorgeIpardoned7criminals:inoculated;1laywithsmallpoxvictimeverynighttoend.Allrecovered.Repeatedwith6morecriminals+5orphans.Then2daughtersofPrince&PrincessofWalesinoculated,hencebecamepopular.7ImmunisationagainstSmallpox(2)VaccinationEndof18thC.:EdwardJennerInoculated7subjectswithcowpox.2challengedwithsmallpox.AllO.K.Cowpox=Vacciniavirus,hencevaccinationgeneralterm.8EdwardJennerinoculatingJamesPhippswithcowpox910ImmunisationagainstSmallpox(3)WHOProgramme1978:WHOProgrammecompleted.Smallpoxcompletelyeradicatedworldwide.1119thC.:BacteriacausediseaseRobertKoch&LouisPasteurestablishedbacteriaascauseofdiseases.Pasteur:Injectedanimalswithliveattenuatedmicoorganismsimmunityv.chickencholera,anthrax,rabies.12WarsofTheCellsandAntibodiesCellularTheory:ElieMetchnikoffPhagocytesinstarfishlarvaesurroundasplinter;phagocytosis&digestionofbacteriabyMs&polymorphsPhagocyticTheory(innateimmunity).G.B.Shaw,“TheDoctor’sDilemma”:“….stimulatethephagocytes”.HumoralTheory:Koch,Ehrlichetal.(Berlin)Showedserumfromimmunisedanimalskillsbacteria.13IlyaMetchnikoff14HumoralImmunityBordetdiscoveredcomplement.Behring&Kitasato–immunitytodiphtheria&tetanusduetoAbs.v.toxins.Passivetf.ofimmuneserumprotection=1stimmunotherapy.1516WarsofTheCellsandAntibodies:TruceSirAlmothWright&Douglas-OpsonisationofbacteriabyAbs.AttemptedfusionofCellularandHumoralTheories–“SirAlmostRight”.Littleprogressincellularimmunologyfor50years(unfashionable).1720thC:HowareAbs.made?Selectivev.InstructiveTheoriesAreAbspre-made(selective)or“moulded”byag(instructive)?Ehrlich’sSideChainTheory(selective)Pauling-InstructiveTheorySirMacFarlaneBurnet–ClonalSelectionTheory.1819ChemicalapproachtoAbs.&Ags.Landsteiner:Specificity&diversity;bloodgroupags.AbsasproteinsPorter&Edelman:1stDescriptionofstructureofIgG20R.R.Porter21ReturntoCellularTheories(InparallelwithstudiesofAbs.)Humoralimmunitycannotexplaingraftrejection,tolerance,immunitytoviruses.Medawar–tolerancetoskinallograftsRoleofT-cells:Thcells(T-Bcellcooperation),Tccells(killvirusinfectedcells).Zinkernagel&Doherty–Tcrecogniseag.boundtoMHC221975–present:TheMolecularRevolution(1)Köhler&Milstein:MonoclonalAbsNobelPrize1984231975–present:TheMolecularRevolution(2)Tonegawa–geneticbasisofAbvariabilityPCR&genecloningtechniques+Mabs.identification,structure&functionofIg&TCRgenes,cellsurfaceags.&cytokines.241975–present:TheMolecularRevolution(3)Geneticmanipulation:GeneK.O.andtransgenicmiceenablestudyofeffectsofmolecularcomponentsofI.S.,signallingpathwaysetc.ApplicationstoDisease:MAbsfordiagnosis&immunotherapy;recombinant&DNAvaccines;genetherapy