1、The History of ImmunologynJr.Hons.Immunology B.Sc.nD.I.Stott“He who ignores history is doomed to repeat it.”1Stages of ImmunologynDescriptive early periodnEarly attempts at vaccination:SmallpoxnEarly experiments:Bacteria cause diseasenHumoral v.cellular immunitynSelective v.instructive theories of I
2、.R.nThe molecular revolution present2Descriptive Early PeriodnPlagues&pandemics,esp.bubonic plague(Pasteurella pestis)&smallpox.nCauses of disease unknown until 19th C.Thought to be caused by poisons=“virus”(latin).nThucydides(5thC.B.C.):people who recovered-immune3Early Attempts at ImmunisationnMit
3、hradates VI(Anatolian King)took increasing daily doses of poisons.nImmunisation against Smallpox:-nChinese:dried matter from pustules inserted in nostrils.nTurks:used variolation,hence Variola Virus.4A Smallpox Victim5Immunisation against Smallpox(1)VariolationnEarly 18th C.:Lady Mary Wortley Montag
4、u(wife of British Ambassador,Constantinople)inoculated own children.n“The Royal Experiment”George I pardoned 7 criminals:inoculated;1 lay with smallpox victim every night to end.All recovered.Repeated with 6 more criminals+5 orphans.Then 2 daughters of Prince&Princess of Wales inoculated,hence becam
5、e popular.6Immunisation against Smallpox(2)VaccinationnEnd of 18th C.:Edward JennernInoculated 7 subjects with cowpox.2 challenged with smallpox.All O.K.nCowpox=Vaccinia virus,hence vaccination general term.7Edward Jenner inoculating James Phipps with cowpox89Immunisation against Smallpox(3)WHO Prog
6、rammen1978:WHO Programme completed.Smallpox completely eradicated worldwide.1019th C.:Bacteria cause diseasenRobert Koch&Louis Pasteur established bacteria as cause of diseases.nPasteur:Injected animals with live attenuated micoorganisms immunity v.chicken cholera,anthrax,rabies.11Wars of The Cells
7、and AntibodiesnCellular Theory:Elie Metchnikoff Phagocytes in starfish larvae surround a splinter;phagocytosis&digestion of bacteria by Ms&polymorphs Phagocytic Theory(innate immunity).nG.B.Shaw,“The Doctors Dilemma”:“.stimulate the phagocytes”.nHumoral Theory:Koch,Ehrlich et al.(Berlin)nShowed seru
8、m from immunised animals kills bacteria.12Ilya Metchnikoff13Humoral ImmunitynBordet discovered complement.nBehring&Kitasato immunity to diphtheria&tetanus due to Abs.v.toxins.Passive tf.of immune serum protection=1st immunotherapy.1415Wars of The Cells and Antibodies:TrucenSir Almoth Wright&Douglas-
9、Opsonisation of bacteria by Abs.Attempted fusion of Cellular and Humoral Theories “Sir Almost Right”.nLittle progress in cellular immunology for 50 years(unfashionable).1620th C:How are Abs.made?Selective v.Instructive TheoriesnAre Abs pre-made(selective)or“moulded”by ag(instructive)?nEhrlichs Side
10、Chain Theory(selective)nPauling-Instructive Theory nSir MacFarlane Burnet Clonal Selection Theory.1718Chemical approach to Abs.&Ags.nLandsteiner:Specificity&diversity;blood group ags.nAbs as proteinsnPorter&Edelman:1st Description of structure of IgG19R.R.Porter20Return to Cellular Theories(In paral
11、lel with studies of Abs.)nHumoral immunity cannot explain graft rejection,tolerance,immunity to viruses.nMedawar tolerance to skin allograftsnRole of T-cells:Th cells(T-B cell cooperation),Tc cells(kill virus infected cells).nZinkernagel&Doherty Tc recognise ag.bound to MHC211975 present:The Molecular Revolution(1)nKhler&Milstein:Monoclonal AbsNobel Prize 1984221975 present:The Molecular Revolution(2)nTonegawa genetic basis of Ab variabilitynPCR&gene cloning techniques+Mabs.identification,structure&function of Ig&TCR genes,cell surface ags.&cytokines.23
