免疫学发展史History_精品文档.ppt

免疫学发展史History_精品文档.ppt

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

SmallpoxnEarlyexperiments:

BacteriacausediseasenHumoralv.cellularimmunitynSelectivev.instructivetheoriesofI.R.nThemolecularrevolutionpresent2DescriptiveEarlyPeriodnPlagues&pandemics,esp.bubonicplague（Pasteurellapestis）&smallpox.nCausesofdiseaseunknownuntil19thC.Thoughttobecausedbypoisons=“virus”（latin）.nThucydides（5thC.B.C.）:

peoplewhorecovered-immune3EarlyAttemptsatImmunisationnMithradatesVI（AnatolianKing）tookincreasingdailydosesofpoisons.nImmunisationagainstSmallpox:

-nChinese:

driedmatterfrompustulesinsertedinnostrils.nTurks:

usedvariolation,henceVariolaVirus.4ASmallpoxVictim5ImmunisationagainstSmallpox

（1）VariolationnEarly18thC.:

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

inoculated;1laywithsmallpoxvictimeverynighttoend.Allrecovered.Repeatedwith6morecriminals+5orphans.Then2daughtersofPrince&PrincessofWalesinoculated,hencebecamepopular.6ImmunisationagainstSmallpox

（2）VaccinationnEndof18thC.:

EdwardJennernInoculated7subjectswithcowpox.2challengedwithsmallpox.AllO.K.nCowpox=Vacciniavirus,hencevaccinationgeneralterm.7EdwardJennerinoculatingJamesPhippswithcowpox89ImmunisationagainstSmallpox（3）WHOProgrammen1978:

WHOProgrammecompleted.Smallpoxcompletelyeradicatedworldwide.1019thC.:

BacteriacausediseasenRobertKoch&LouisPasteurestablishedbacteriaascauseofdiseases.nPasteur:

Injectedanimalswithliveattenuatedmicoorganismsimmunityv.chickencholera,anthrax,rabies.11WarsofTheCellsandAntibodiesnCellularTheory:

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

“.stimulatethephagocytes”.nHumoralTheory:

Koch,Ehrlichetal.（Berlin）nShowedserumfromimmunisedanimalskillsbacteria.12IlyaMetchnikoff13HumoralImmunitynBordetdiscoveredcomplement.nBehring&Kitasatoimmunitytodiphtheria&tetanusduetoAbs.v.toxins.Passivetf.ofimmuneserumprotection=1stimmunotherapy.1415WarsofTheCellsandAntibodies:

TrucenSirAlmothWright&Douglas-OpsonisationofbacteriabyAbs.AttemptedfusionofCellularandHumoralTheories“SirAlmostRight”.nLittleprogressincellularimmunologyfor50years（unfashionable）.1620thC:

HowareAbs.made?

Selectivev.InstructiveTheoriesnAreAbspre-made（selective）or“moulded”byag（instructive）?

nEhrlichsSideChainTheory（selective）nPauling-InstructiveTheorynSirMacFarlaneBurnetClonalSelectionTheory.1718ChemicalapproachtoAbs.&Ags.nLandsteiner:

Specificity&diversity;bloodgroupags.nAbsasproteinsnPorter&Edelman:

1stDescriptionofstructureofIgG19R.R.Porter20ReturntoCellularTheories（InparallelwithstudiesofAbs.）nHumoralimmunitycannotexplaingraftrejection,tolerance,immunitytoviruses.nMedawartolerancetoskinallograftsnRoleofT-cells:

Thcells（T-Bcellcooperation）,Tccells（killvirusinfectedcells）.nZinkernagel&DohertyTcrecogniseag.boundtoMHC211975present:

TheMolecularRevolution

（1）nKhler&Milstein:

MonoclonalAbsNobelPrize1984221975present:

TheMolecularRevolution

（2）nTonegawageneticbasisofAbvariabilitynPCR&genecloningtechniques+Mabs.identification,structure&functionofIg&TCRgenes,cellsurfaceags.&cytokines.231975present:

TheMolecularRevolution（3）nGeneticmanipulation:

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

MAbsfordiagnosis&immunotherapy;recombinant&DNAvaccines;genetherapy24