免疫学发展史History.ppt

1、1,The History of Immunology,Jr.Hons.Immunology B.Sc.D.I.Stott,“He who ignores history is doomed to repeat it.”,2,Stages of Immunology,Descriptive early periodEarly attempts at vaccination:SmallpoxEarly experiments:Bacteria cause diseaseHumoral v.cellular immunitySelective v.instructive theories of I

2、.R.The molecular revolution present,3,Descriptive Early Period,Plagues&pandemics,esp.bubonic plague(Pasteurella pestis)&smallpox.Causes of disease unknown until 19th C.Thought to be caused by poisons=“virus”(latin).Thucydides(5thC.B.C.):people who recovered-immune,4,Early Attempts at Immunisation,Mi

3、thradates VI(Anatolian King)took increasing daily doses of poisons.Immunisation against Smallpox:-Chinese:dried matter from pustules inserted in nostrils.Turks:used variolation,hence Variola Virus.,5,A Smallpox Victim,6,Immunisation against Smallpox(1)Variolation,Early 18th C.:Lady Mary Wortley Mont

4、agu(wife of British Ambassador,Constantinople)inoculated own children.“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 beca

5、me popular.,7,Immunisation against Smallpox(2)Vaccination,End of 18th C.:Edward JennerInoculated 7 subjects with cowpox.2 challenged with smallpox.All O.K.Cowpox=Vaccinia virus,hence vaccination general term.,8,Edward Jenner inoculating James Phipps with cowpox,9,10,Immunisation against Smallpox(3)W

6、HO Programme,1978:WHO Programme completed.,Smallpox completely eradicated worldwide.,11,19th C.:Bacteria cause disease,Robert Koch&Louis Pasteur established bacteria as cause of diseases.Pasteur:Injected animals with live attenuated micoorganisms immunity v.chicken cholera,anthrax,rabies.,12,Wars of

7、 The Cells and Antibodies,Cellular Theory:Elie Metchnikoff Phagocytes in starfish larvae surround a splinter;phagocytosis&digestion of bacteria by Ms&polymorphs Phagocytic Theory(innate immunity).G.B.Shaw,“The Doctors Dilemma”:“.stimulate the phagocytes”.Humoral Theory:Koch,Ehrlich et al.(Berlin)Sho

8、wed serum from immunised animals kills bacteria.,13,Ilya Metchnikoff,14,Humoral Immunity,Bordet discovered complement.Behring&Kitasato immunity to diphtheria&tetanus due to Abs.v.toxins.Passive tf.of immune serum protection=1st immunotherapy.,15,16,Wars of The Cells and Antibodies:Truce,Sir Almoth W

9、right&Douglas-Opsonisation of bacteria by Abs.Attempted fusion of Cellular and Humoral Theories“Sir Almost Right”.Little progress in cellular immunology for 50 years(unfashionable).,17,20th C:How are Abs.made?Selective v.Instructive Theories,Are Abs pre-made(selective)or“moulded”by ag(instructive)?E

10、hrlichs Side Chain Theory(selective)Pauling-Instructive TheorySir MacFarlane Burnet Clonal Selection Theory.,18,19,Chemical approach to Abs.&Ags.,Landsteiner:Specificity blood group ags.Abs as proteinsPorter&Edelman:1st Description of structure of IgG,20,R.R.Porter,21,Return to Cellular Theories,(In

11、 parallel with studies of Abs.)Humoral immunity cannot explain graft rejection,tolerance,immunity to viruses.Medawar tolerance to skin allograftsRole of T-cells:Th cells(T-B cell cooperation),Tc cells(kill virus infected cells).Zinkernagel&Doherty Tc recognise ag.bound to MHC,22,1975 present:The Mol

12、ecular Revolution(1),Khler&Milstein:Monoclonal Abs,Nobel Prize 1984,23,1975 present:The Molecular Revolution(2),Tonegawa genetic basis of Ab variabilityPCR&gene cloning techniques+Mabs.identification,structure&function of Ig&TCR genes,cell surface ags.&cytokines.,24,1975 present:The Molecular Revolution(3),Genetic manipulation:Gene K.O.and transgenic mice enable study of effects of molecular components of I.S.,signalling pathways etc.Applications to Disease:MAbs for diagnosis gene therapy,