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1TheHistoryofImmunologyJr.Hons.ImmunologyB.Sc.D.I.Stott“Hewhoignoreshistoryisdoomedtorepeatit.”

1TheHistoryofImmunologyJr.2StagesofImmunologyDescriptiveearlyperiodEarlyattemptsatvaccination:SmallpoxEarlyexperiments:BacteriacausediseaseHumoralv.cellularimmunitySelectivev.instructivetheoriesofI.R.Themolecularrevolutionpresent2StagesofImmunologyDescripti3DescriptiveEarlyPeriodPlagues&pandemics,esp.bubonicplague(Pasteurellapestis)&smallpox.Causesofdiseaseunknownuntil19thC.Thoughttobecausedbypoisons=“virus”(latin).

Thucydides(5thC.B.C.):peoplewhorecovered-immune3DescriptiveEarlyPeriodPlagu4EarlyAttemptsatImmunisationMithradatesVI(AnatolianKing)tookincreasingdailydosesofpoisons.ImmunisationagainstSmallpox:-Chinese:driedmatterfrompustulesinsertedinnostrils.Turks:usedvariolation,henceVariolaVirus.4EarlyAttemptsatImmunisatio5ASmallpoxVictim5ASmallpoxVictim6ImmunisationagainstSmallpox

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

6ImmunisationagainstSmallpox7ImmunisationagainstSmallpox

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

Cowpox=Vacciniavirus,hencevaccinationgeneralterm.7ImmunisationagainstSmallpoxMedawar–tolerancetoskinallograftsCellularTheory:ElieMetchnikoff Phagocytesinstarfishlarvaesurroundasplinter;phagocytosis&digestionofbacteriabyMs&polymorphsPhagocyticTheory(innateimmunity).Passivetf.Causesofdiseaseunknownuntil19thC.Chinese:driedmatterfrompustulesinsertedinnostrils.Causesofdiseaseunknownuntil19thC.20thC:HowareAbs.EdwardJennerinoculatingJamesPhippswithcowpoxImmunisationagainstSmallpox

(2) VaccinationRoleofT-cells:Thcells(T-Bcellcooperation),Tccells(killvirusinfectedcells).Repeatedwith6morecriminals+5orphans.AbsasproteinsInoculated7subjectswithcowpox.EdwardJennerinoculatingJamesPhippswithcowpox20thC:HowareAbs.stimulatethephagocytes”.Absasproteinsofimmuneserumprotection=1stimmunotherapy.InstructiveTheoriesmade?Selectivev.8EdwardJennerinoculatingJamesPhippswithcowpoxMedawar–tolerancetoskinal9910ImmunisationagainstSmallpox(3)WHOProgramme1978:WHOProgrammecompleted.Smallpoxcompletelyeradicatedworldwide.10ImmunisationagainstSmallpo1119thC.:BacteriacausediseaseRobertKoch&LouisPasteurestablishedbacteriaascauseofdiseases.Pasteur:Injectedanimalswithliveattenuatedmicoorganismsimmunityv.chickencholera,anthrax,rabies.

1119thC.:Bacteriacausedise12WarsofTheCellsandAntibodiesCellularTheory:ElieMetchnikoff Phagocytesinstarfishlarvaesurroundasplinter;phagocytosis&digestionofbacteriabyMs&polymorphs

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

Koch,Ehrlichetal.(Berlin)Showedserumfromimmunisedanimalskillsbacteria.12WarsofTheCellsandAntibo13IlyaMetchnikoff13IlyaMetchnikoff14HumoralImmunityBordetdiscoveredcomplement.Behring&Kitasato–immunitytodiphtheria&tetanusduetoAbs.v.toxins.Passivetf.ofimmuneserumprotection=1stimmunotherapy.

14HumoralImmunityBordetdisco151516WarsofTheCellsandAntibodies:TruceSirAlmothWright&Douglas-OpsonisationofbacteriabyAbs.AttemptedfusionofCellularandHumoralTheories–“SirAlmostRight”.Littleprogressincellularimmunologyfor50years(unfashionable).

16WarsofTheCellsandAntibo1720thC:HowareAbs.made?Selectivev.InstructiveTheoriesAreAbspre-made(selective)or“moulded”byag(instructive)?Ehrlich’sSideChainTheory(selective)Pauling-InstructiveTheory

SirMacFarlaneBurnet–ClonalSelectionTheory.1720thC:HowareAbs.made?1818AttemptedfusionofCellularandHumoralTheories–“SirAlmostRight”.SirMacFarlaneBurnet–ClonalSelectionTheory.AbsasproteinsPlagues&pandemics,esp.Causesofdiseaseunknownuntil19thC.made?Selectivev.Littleprogressincellularimmunologyfor50years(unfashionable).):peoplewhorecovered-immuneGeneticmanipulation:GeneK.20thC:HowareAbs.Earlyexperiments:BacteriacausediseaseHumoralTheory:Koch,Ehrlichetal.chickencholera,anthrax,rabies.TheHistoryofImmunologyNobelPrize1984):peoplewhorecovered-immunePCR&genecloningtechniques+Mabs.,signallingpathwaysetc.Repeatedwith6morecriminals+5orphans.Smallpoxcompletelyeradicatedworldwide.boundtoMHC19ChemicalapproachtoAbs.&Ags.Landsteiner:Specificity&diversity;bloodgroupags.AbsasproteinsPorter&Edelman:1stDescriptionofstructureofIgGAttemptedfusionofCellulara20R.R.Porter20R.R.Porter21ReturntoCellularTheories(InparallelwithstudiesofAbs.)Humoralimmunitycannotexplaingraftrejection,tolerance,immunitytoviruses.

Medawar–tolerancetoskinallograftsRoleofT-cells:Thcells(T-Bcellcooperation),Tccells(killvirusinfectedcells).Zinkernagel&Doherty–Tcrecogniseag.boundtoMHC21ReturntoCellularTheories221975–present:TheMolecularRevolution(1)K?hler&Milstein:MonoclonalAbsNobelPrize1984221975–present:TheMolecula231975–present:TheMolecularRevolution(2)Tonegawa–geneticbasisofAbvariabilityPCR&genecloningtechniques+Mabs.identification,structure&functionofIg&TCRgenes,cellsurfaceags.&cytokines.

231975–present:TheMolecula241975–present:TheMolecularRevolution(3)Geneticmanipulation:GeneK.O.andtransgenicmiceenablestudyofeffectsofmolecularcomponentsofI.S.,signallingpathwaysetc.ApplicationstoDisease:MAbsfordiagnosis&immunotherapy;recombinant&DNAvaccines;genetherapy241975–present:TheMolecula25ASmallpoxVictim25ASmallpoxVictim26EdwardJennerinoculatingJamesPhippswithcowpox26EdwardJennerinoculatingJa27272820thC:HowareAbs.made?Selectivev.InstructiveTheoriesAreAbspre-made(selective)or“moulded”byag(instructive)?Ehrlich’sSideChainTheory(selective)Pauling-InstructiveTheory

SirMacFarlaneBurnet–ClonalSelectionTheory.2820thC:HowareAbs.made?EdwardJennerinoculatingJamesPhippswithcowpoxReturntoCellularTheoriesTheHistoryofImmunologyCausesofdiseaseunknownuntil19thC.Behring&Kitasato–immunitytodiphtheria&tetanusduetoAbs.Littleprogressincellularimmunologyfor50years(unfashionable).20thC:HowareAbs.Plagues&pandemics,esp.GeorgeIpardoned7criminals:inoculated;1laywithsmallpoxvictimeverynighttoend.1975–present:TheMolecularRevolution(1)ImmunisationagainstSmallpox(3)WHOProgrammeCellularTheory:ElieMetchnikoff Phagocytesinstarfishlarvaesurroundasplinter;phagocytosis&digestionofbacteriabyMs&polymorphsPhagocyticTheory(innateimmunity).20thC:HowareAbs.1975–present:TheMolecularRevolution(3)TheHistoryofImmunologyCausesofdiseaseunknownuntil19thC.boundtoMHCShaw,“TheDoctor’sDilemma”:“….Plagues&pandemics,esp.TheHistoryofImmunologyRepeatedwith6morecriminals+5orphans.Causesofdiseaseunknownuntil19thC.1975–present:TheMolecularRevolution(3)SirMacFarlaneBurnet–ClonalSelectionTheory.Porter&Edelman:1stDescriptionofstructureofIgG1975–present:TheMolecularRevolution(2)andtransgenicmiceenablestudyofeffectsofmolecularcomponentsofI.Geneticmanipulation:GeneK.:BacteriacausediseaseHumoralImmunityPorter&Edelman:1stDescriptionofstructureofIgGSirMacFarlaneBurnet–ClonalSelectionTheory.ImmunologyB.ReturntoCellularTheoriesidentification,structure&functionofIg&TCRgenes,cellsurfaceags.K?hler&Milstein:MonoclonalAbs):peoplewhorecovered-immuneEhrlich’sSideChainTheory(selective)ofimmuneserumprotection=1stimmunotherapy.1978:WHOProgrammecompleted.andtransgenicmiceenablestudyofeffectsofmolecularcomponentsofI.DescriptiveEarlyPeriod29R.R.PorterEdwardJennerinoculatingJamestimulatethephagocytes”.Repeatedwith6morecriminals+5orphans.andtransgenicmiceenablestudyofeffectsofmolecularcomponentsofI.EdwardJennerinoculatingJamesPhippswithcowpoxImmunisationagainstSmallpox(3)WHOProgrammeImmunologyB.made?Selectivev.):peoplewhorecovered-immuneCausesofdiseaseunknownuntil19thC.Causesofdiseaseunknownuntil19thC.ASmallpoxVictimGeorgeIpardoned7criminals:inoculated;1laywithsmallpoxvictimeverynighttoend.AbsasproteinsPauling-InstructiveTheoryCellularTheory:ElieMetchnikoff Phagocytesinstarfishlarvaesurroundasplinter;phagocytosis&digestionofbacteriabyMs&polymorphsPhagocyticTheory(innateimmunity).Then2daughtersofPrince&PrincessofWalesinoculated,hencebecamepopular.ofimmuneserumprotection=1stimmunotherapy.1975–present:TheMolecularRevolution(3)Humoralimmunitycannotexplaingraftrejection,tolerance,immunitytoviruses.ImmunisationagainstSmallpox

(1) VariolationCellularTheory:ElieMetchnikoff Phagocytesinstarfishlarvaesurroundasplinter;phagocytosis&digestionofbacteriabyMs&polymorphsPhagocyticTheory(innateimmunity).):peoplewhorecovered-immunePlagues&pandemics,esp.Passivetf.Causesofdiseaseunknownuntil19thC.EarlyAttemptsatImmunisationmade?Selectivev.Thucydides(5thC.1975–present:TheMolecularRevolution(2)identification,structure&functionofIg&TCRgenes,cellsurfaceags.Showedserumfromimmunisedanimalskillsbacteria.ofimmuneserumprotection=1stimmunotherapy.Behring&Kitasato–immunitytodiphtheria&tetanusduetoAbs.Medawar–tolerancetoskinallograftsboundtoMHC1975–present:TheMolecularRevolution(3)Earlyexperiments:BacteriacausediseaseZinkernagel&Doherty–Tcrecogniseag.TheHistoryofImmunologyPCR&genecloningtechniques+Mabs.ImmunisationagainstSmallpox:-20thC:HowareAbs.Showedserumfromimmunisedanimalskillsbacteria.301975–present:TheMolecularRevolution(2)Tonegawa–geneticbasisofAbvariabilityPCR&genecloningtechniques+Mabs.identification,structure&functionofIg&TCRgenes,cellsurfaceags.&cytokines.

stimulatethephagocytes”.):p31TheHistoryofImmunologyJr.Hons.ImmunologyB.Sc.D.I.Stott“Hewhoignoreshistoryisdoomedtorepeatit.”

1TheHistoryofImmunologyJr.32StagesofImmunologyDescriptiveearlyperiodEarlyattemptsatvaccination:SmallpoxEarlyexperiments:BacteriacausediseaseHumoralv.cellularimmunitySelectivev.instructivetheoriesofI.R.Themolecularrevolutionpresent2StagesofImmunologyDescripti33DescriptiveEarlyPeriodPlagues&pandemics,esp.bubonicplague(Pasteurellapestis)&smallpox.Causesofdiseaseunknownuntil19thC.Thoughttobecausedbypoisons=“virus”(latin).

Thucydides(5thC.B.C.):peoplewhorecovered-immune3DescriptiveEarlyPeriodPlagu34EarlyAttemptsatImmunisationMithradatesVI(AnatolianKing)tookincreasingdailydosesofpoisons.ImmunisationagainstSmallpox:-Chinese:driedmatterfrompustulesinsertedinnostrils.Turks:usedvariolation,henceVariolaVirus.4EarlyAttemptsatImmunisatio35ASmallpoxVictim5ASmallpoxVictim36ImmunisationagainstSmallpox

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

6ImmunisationagainstSmallpox37ImmunisationagainstSmallpox

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

Cowpox=Vacciniavirus,hencevaccinationgeneralterm.7ImmunisationagainstSmallpoxMedawar–tolerancetoskinallograftsCellularTheory:ElieMetchnikoff Phagocytesinstarfishlarvaesurroundasplinter;phagocytosis&digestionofbacteriabyMs&polymorphsPhagocyticTheory(innateimmunity).Passivetf.Causesofdiseaseunknownuntil19thC.Chinese:driedmatterfrompustulesinsertedinnostrils.Causesofdiseaseunknownuntil19thC.20thC:HowareAbs.EdwardJennerinoculatingJamesPhippswithcowpoxImmunisationagainstSmallpox

(2) VaccinationRoleofT-cells:Thcells(T-Bcellcooperation),Tccells(killvirusinfectedcells).Repeatedwith6morecriminals+5orphans.AbsasproteinsInoculated7subjectswithcowpox.EdwardJennerinoculatingJamesPhippswithcowpox20thC:HowareAbs.stimulatethephagocytes”.Absasproteinsofimmuneserumprotection=1stimmunotherapy.InstructiveTheoriesmade?Selectivev.38EdwardJennerinoculatingJamesPhippswithcowpoxMedawar–tolerancetoskinal39940ImmunisationagainstSmallpox(3)WHOProgramme1978:WHOProgrammecompleted.Smallpoxcompletelyeradicatedworldwide.10ImmunisationagainstSmallpo4119thC.:BacteriacausediseaseRobertKoch&LouisPasteurestablishedbacteriaascauseofdiseases.Pasteur:Injectedanimalswithliveattenuatedmicoorganismsimmunityv.chickencholera,anthrax,rabies.

1119thC.:Bacteriacausedise42WarsofTheCellsandAntibodiesCellularTheory:ElieMetchnikoff Phagocytesinstarfishlarvaesurroundasplinter;phagocytosis&digestionofbacteriabyMs&polymorphs

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

Koch,Ehrlichetal.(Berlin)Showedserumfromimmunisedanimalskillsbacteria.12WarsofTheCellsandAntibo43IlyaMetchnikoff13IlyaMetchnikoff44HumoralImmunityBordetdiscoveredcomplement.Behring&Kitasato–immunitytodiphtheria&tetanusduetoAbs.v.toxins.Passivetf.ofimmuneserumprotection=1stimmunotherapy.

14HumoralImmunityBordetdisco451546WarsofTheCellsandAntibodies:TruceSirAlmothWright&Douglas-OpsonisationofbacteriabyAbs.AttemptedfusionofCellularandHumoralTheories–“SirAlmostRight”.Littleprogressincellularimmunologyfor50years(unfashionable).

16WarsofTheCellsandAntibo4720thC:HowareAbs.made?Selectivev.InstructiveTheoriesAreAbspre-made(selective)or“moulded”byag(instructive)?Ehrlich’sSideChainTheory(selective)Pauling-InstructiveTheory

SirMacFarlaneBurnet–ClonalSelectionTheory.1720thC:HowareAbs.made?4818AttemptedfusionofCellularandHumoralTheories–“SirAlmostRight”.SirMacFarlaneBurnet–ClonalSelectionTheory.AbsasproteinsPlagues&pandemics,esp.Causesofdiseaseunknownuntil19thC.made?Selectivev.Littleprogressincellularimmunologyfor50years(unfashionable).):peoplewhorecovered-immuneGeneticmanipulation:GeneK.20thC:HowareAbs.Earlyexperiments:BacteriacausediseaseHumoralTheory:Koch,Ehrlichetal.chickencholera,anthrax,rabies.TheHistoryofImmunologyNobelPrize1984):peoplewhorecovered-immunePCR&genecloningtechniques+Mabs.,signallingpathwaysetc.Repeatedwith6morecriminals+5orphans.Smallpoxcompletelyeradicatedworldwide.boundtoMHC49ChemicalapproachtoAbs.&Ags.Landsteiner:Specificity&diversity;bloodgroupags.AbsasproteinsPorter&Edelman:1stDescriptionofstructureofIgGAttemptedfusionofCellulara50R.R.Porter20R.R.Porter51ReturntoCellularTheories(InparallelwithstudiesofAbs.)Humoralimmunitycannotexplaingraftrejection,tolerance,immunitytoviruses.

Medawar–tolerancetoskinallograftsRoleofT-cells:Thcells(T-Bcellcooperation),Tccells(killvirusinfectedcells).Zinkernagel&Doherty–Tcrecogniseag.boundtoMHC21ReturntoCellularTheories521975–present:TheMolecularRevolution(1)K?hler&Milstein:MonoclonalAbsNobelPrize1984221975–present:TheMolecula531975–present:TheMolecularRevolution(2)Tonegawa–geneticbasisofAbvariabilityPCR&genecloningtechniques+Mabs.identification,structure&functionofIg&TCRgenes,cellsurfaceags.&cytokines.

231975–present:TheMolecula541975–present:TheMolecularRevolution(3)Geneticmanipulation:GeneK.O.andtransgenicmiceenablestudyofeffectsofmolecularcomponentsofI.S.,signallingpathwaysetc.ApplicationstoDisease:MAbsfordiagnosis&immunotherapy;recombinant&DNAvaccines;genetherapy241975–present:TheMolecula55ASmallpoxVictim25ASmallpoxVictim56EdwardJennerinoculatingJamesPhippswithcowpox26EdwardJennerinoculatingJa57275820thC:HowareAbs.made?Selectivev.InstructiveTheoriesAreAbspre-made(selective)or“moulded”byag(instructive)?Ehrlich’sSideChainTheory(selective)Pauling-InstructiveTheory

SirMacFarlaneBurnet–ClonalSelectionTheory.2820thC:HowareAbs.made?EdwardJennerinoculatingJamesPhippswithcowpoxReturntoCellularTheoriesTheHistoryofImmunologyCausesofdiseaseunknownuntil19thC.Behring&Kitasato–immunitytodiphtheria&tetanusduetoAbs.Littleprogressincellularimmunologyfor50years(unfashionable).20thC:HowareAbs.Plagues&pandemics,esp.GeorgeIpardoned7criminals:inoculated;1laywithsmallpoxvictimeverynighttoend.1975–present:TheMolecularRevolution(1)ImmunisationagainstSmallpox(3)WHOProgrammeCellularTheory:ElieMetchnikoff Phagocytesinstarfishlarvaesurroundasplinter;phagocytosis&digestionofbacteriabyMs&polymorphsPhagocyticTheory(innateimmunity).20thC:HowareAbs.1975–present:TheMolecularRevolution(3)TheHistoryofImmunologyCausesofdiseaseunknownuntil19thC.boundtoMHCShaw,“TheDoctor’sDilemma”:“….Plagues&pandemics,esp.TheHistoryofImmunologyRepeatedwith6morecriminals+5orphans.Causesofdiseaseunknownuntil19thC.1975–present:TheMolecularRevolution(3)SirMacFarlaneBurnet–ClonalSelectionTheory.Porter&Edelman:1stDescriptionofstructureofIgG1975–present:TheMolecularRevolution(2)andtransgenicmiceenablestudyofeffectsofmolecularcomponentsofI.Geneticmanipulation:GeneK.:BacteriacausediseaseHumoralImmunityPorter&Edelman:1stDescriptionofstructureofIgGSirMacFarlaneBurnet–ClonalSelectionTheory.ImmunologyB.ReturntoCellularTheoriesidentification,structure&functionofIg&TCRgenes,cellsurfaceags.K?hler&Milstein:MonoclonalAbs):peoplewhorecovered-immuneEhrlich’sSideChainTheory(selective)ofimmuneserumprotection=1stimmunotherapy.1978:WHOProgrammecompleted.andtransgenicmiceenablestudyofeffectsofmolecularcomponentsofI.DescriptiveEarlyPeriod59R.R.PorterEdwardJennerinoculatingJamestimulatethephagocytes”.Repeatedwith6morecriminals+5orphans.andtransgenic

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