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1、The History of ImmunologyJr. Hons. Immunology B.Sc.D. I. Stott“He who ignores history is doomed to repeat it.”1The History of ImmunologyJr. HStages of ImmunologyDescriptive early periodEarly attempts at vaccination: SmallpoxEarly experiments: Bacteria cause diseaseHumoral v. cellular immunitySelecti

2、ve v. instructive theories of I.R.The molecular revolution present2Stages of ImmunologyDescriptivDescriptive Early PeriodPlagues & pandemics, esp. bubonic plague (Pasteurella pestis) & smallpox.Causes of disease unknown until 19th C. Thought to be caused by poisons = “virus” (latin). Thucydides (5th

3、C. B.C.): people who recovered - immune3Descriptive Early PeriodPlagueEarly Attempts at ImmunisationMithradates 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 Vi

4、rus.4Early Attempts at ImmunisationA Smallpox Victim5A Smallpox Victim5Immunisation against Smallpox (1)VariolationEarly 18th C.: Lady Mary Wortley Montagu (wife of British Ambassador, Constantinople) inoculated own children. “The Royal Experiment”George I pardoned 7 criminals: inoculated; 1 lay wit

5、h 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 became popular.6Immunisation against Smallpox Immunisation against Smallpox (2)VaccinationEnd of 18th C.: Edward JennerInoculated 7 subject

6、s with cowpox. 2 challenged with smallpox. All O.K. Cowpox = Vaccinia virus, hence vaccination general term.7Immunisation against Smallpox Edward Jenner inoculating James Phipps with cowpox8Edward Jenner inoculating Jame99Immunisation against Smallpox (3) WHO Programme1978: WHO Programme completed.S

7、mallpox completely eradicated worldwide.10Immunisation against Smallpox 19th C.: Bacteria cause diseaseRobert Koch & Louis Pasteur established bacteria as cause of diseases.Pasteur: Injected animals with live attenuated micoorganisms immunity v. chicken cholera, anthrax, rabies. 1119th C.: Bacteria

8、cause diseasWars of The Cells and AntibodiesCellular 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: K

9、och, Ehrlich et al. (Berlin) Showed serum from immunised animals kills bacteria.12Wars of The Cells and AntibodiIlya Metchnikoff13Ilya Metchnikoff13Humoral ImmunityBordet discovered complement.Behring & Kitasato immunity to diphtheria & tetanus due to Abs. v. toxins. Passive tf. of immune serum prot

10、ection = 1st immunotherapy.14Humoral ImmunityBordet discove1515Wars of The Cells and Antibodies: TruceSir Almoth Wright & 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

11、). 16Wars of The Cells and Antibodi20th C: How are Abs. made? Selective v. Instructive TheoriesAre Abs pre-made (selective) or “moulded” by ag (instructive)?Ehrlichs Side Chain Theory (selective)Pauling - Instructive TheorySir MacFarlane Burnet Clonal Selection Theory.1720th C: How are Abs. made? Se

12、1818Chemical approach to Abs. & Ags.Landsteiner: Specificity & diversity; blood group ags.Abs as proteinsPorter & Edelman: 1st Description of structure of IgG19Chemical approach to Abs. & AgR. R. Porter20R. R. Porter20Return to Cellular Theories (In parallel with studies of Abs.)Humoral immunity can

13、not 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 MHC21Return to Cellular Theories (I1975 present: The Molecular Revolution (1)Khler & Milstein: Monoclonal AbsNobel Prize 1984221975 present: The Molecular 1975 present: The Molecu

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