免疫学发展史History.ppt

免疫学发展史History.ppt

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1,TheHistoryofImmunology,Jr.Hons.ImmunologyB.Sc.D.I.Stott,“Hewhoignoreshistoryisdoomedtorepeatit.”,2,StagesofImmunology,DescriptiveearlyperiodEarlyattemptsatvaccination:

SmallpoxEarlyexperiments:

BacteriacausediseaseHumoralv.cellularimmunitySelectivev.instructivetheoriesofI.R.Themolecularrevolutionpresent,3,DescriptiveEarlyPeriod,Plagues&pandemics,esp.bubonicplague（Pasteurellapestis）&smallpox.Causesofdiseaseunknownuntil19thC.Thoughttobecausedbypoisons=“virus”（latin）.Thucydides（5thC.B.C.）:

peoplewhorecovered-immune,4,EarlyAttemptsatImmunisation,MithradatesVI（AnatolianKing）tookincreasingdailydosesofpoisons.ImmunisationagainstSmallpox:

-Chinese:

driedmatterfrompustulesinsertedinnostrils.Turks:

usedvariolation,henceVariolaVirus.,5,ASmallpoxVictim,6,ImmunisationagainstSmallpox

（1）Variolation,Early18thC.:

LadyMaryWortleyMontagu（wifeofBritishAmbassador,Constantinople）inoculatedownchildren.“TheRoyalExperiment”GeorgeIpardoned7criminals:

inoculated;1laywithsmallpoxvictimeverynighttoend.Allrecovered.Repeatedwith6morecriminals+5orphans.Then2daughtersofPrince&PrincessofWalesinoculated,hencebecamepopular.,7,ImmunisationagainstSmallpox

（2）Vaccination,Endof18thC.:

EdwardJennerInoculated7subjectswithcowpox.2challengedwithsmallpox.AllO.K.Cowpox=Vacciniavirus,hencevaccinationgeneralterm.,8,EdwardJennerinoculatingJamesPhippswithcowpox,9,10,ImmunisationagainstSmallpox（3）WHOProgramme,1978:

WHOProgrammecompleted.,Smallpoxcompletelyeradicatedworldwide.,11,19thC.:

Bacteriacausedisease,RobertKoch&LouisPasteurestablishedbacteriaascauseofdiseases.Pasteur:

Injectedanimalswithliveattenuatedmicoorganismsimmunityv.chickencholera,anthrax,rabies.,12,WarsofTheCellsandAntibodies,CellularTheory:

ElieMetchnikoffPhagocytesinstarfishlarvaesurroundasplinter;phagocytosis&digestionofbacteriabyMs&polymorphsPhagocyticTheory（innateimmunity）.G.B.Shaw,“TheDoctorsDilemma”:

“.stimulatethephagocytes”.HumoralTheory:

Koch,Ehrlichetal.（Berlin）Showedserumfromimmunisedanimalskillsbacteria.,13,IlyaMetchnikoff,14,HumoralImmunity,Bordetdiscoveredcomplement.Behring&Kitasatoimmunitytodiphtheria&tetanusduetoAbs.v.toxins.Passivetf.ofimmuneserumprotection=1stimmunotherapy.,15,16,WarsofTheCellsandAntibodies:

Truce,SirAlmothWright&Douglas-OpsonisationofbacteriabyAbs.AttemptedfusionofCellularandHumoralTheories“SirAlmostRight”.Littleprogressincellularimmunologyfor50years（unfashionable）.,17,20thC:

HowareAbs.made?

Selectivev.InstructiveTheories,AreAbspre-made（selective）or“moulded”byag（instructive）?

EhrlichsSideChainTheory（selective）Pauling-InstructiveTheorySirMacFarlaneBurnetClonalSelectionTheory.,18,19,ChemicalapproachtoAbs.&Ags.,Landsteiner:

Specificitybloodgroupags.AbsasproteinsPorter&Edelman:

1stDescriptionofstructureofIgG,20,R.R.Porter,21,ReturntoCellularTheories,（InparallelwithstudiesofAbs.）Humoralimmunitycannotexplaingraftrejection,tolerance,immunitytoviruses.MedawartolerancetoskinallograftsRoleofT-cells:

Thcells（T-Bcellcooperation）,Tccells（killvirusinfectedcells）.Zinkernagel&DohertyTcrecogniseag.boundtoMHC,22,1975present:

TheMolecularRevolution

（1）,Khler&Milstein:

MonoclonalAbs,NobelPrize1984,23,1975present:

TheMolecularRevolution

（2）,TonegawageneticbasisofAbvariabilityPCR&genecloningtechniques+Mabs.identification,structure&functionofIg&TCRgenes,cellsurfaceags.&cytokines.,24,1975present:

TheMolecularRevolution（3）,Geneticmanipulation:

GeneK.O.andtransgenicmiceenablestudyofeffectsofmolecularcomponentsofI.S.,signallingpathwaysetc.ApplicationstoDisease:

MAbsfordiagnosisgenetherapy,