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,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,免疫学发展史History,Stages of Immunology,Descriptive early period,Early attempts at vaccination: Smallpox,Early experiments: Bacteria cause disease,Humoral v. cellular immunity,Selective v. instructive theories of I.R.,The molecular revolution,present,2,Descriptive Early Period,Plagues & pandemics, esp. bubonic plague (,Pasteurella pestis,) & smallpox.,Causes of disease unknown until 19,th,C. Thought to be caused by poisons = “virus” (latin).,Thucydides (5,th,C. B.C.): people who recovered - immune,3,Early Attempts at Immunisation,Mithradates 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.,4,A Smallpox Victim,5,Immunisation against Smallpox (1)Variolation,Early 18,th,C.:,Lady Mary Wortley Montagu,(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 became popular.,6,Immunisation against Smallpox (2)Vaccination,End of 18,th,C.: Edward Jenner,Inoculated 7 subjects with cowpox. 2 challenged with smallpox. All O.K.,Cowpox = Vaccinia virus, hence vaccination,general term.,7,Edward Jenner inoculating James Phipps with cowpox,8,9,Immunisation against Smallpox (3) WHO Programme,1978: WHO Programme completed.,Smallpox completely eradicated worldwide.,10,19,th,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.,11,Wars of The Cells and Antibodies,Cellular Theory: Elie Metchnikoff,Phagocytes in starfish larvae surround a splinter; phagocytosis & digestion of bacteria by M,s & polymorphs,Phagocytic Theory,(innate immunity).,G.B. Shaw, “The Doctors Dilemma”: “.stimulate the phagocytes”.,Humoral Theory:,Koch, Ehrlich,et al. (Berlin),Showed serum from immunised animals kills bacteria.,12,Ilya Metchnikoff,13,Humoral Immunity,Bordet,discovered complement.,Behring & Kitasato, immunity to diphtheria & tetanus due to Abs. v. toxins. Passive tf. of immune serum,protection = 1,st,immunotherapy.,14,15,Wars of The Cells and Antibodies: Truce,Sir 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).,16,20,th,C: How are Abs. made? Selective v. Instructive Theories,Are Abs pre-made (selective) or “moulded” by ag (instructive)?,Ehrlichs,Side Chain Theory (selective),Pauling -,Instructive Theory,Sir MacFarlane Burnet, Clonal Selection Theory.,17,18,Chemical approach to Abs. & Ags.,Landsteiner:,Specificity blood group ags.,Abs as proteins,Porter & Edelman:,1,st,Description of structure of IgG,19,R. R. Porter,20,Return to Cellular Theories,(In parallel with studies of Abs.),Humoral immunity cannot explain graft rejection, tolerance, immunity to viruses.,Medawar, tolerance to skin allografts,Role of T-cells: Th cells (T-B cell cooperation), Tc cells (kill virus infected cells).,Zinkernagel & Doherty, Tc recognise ag. bound to MHC,21,1975 present: The Molecular Revolution (1),Khler & Milstein:,Monoclonal Abs,Nobel Prize 1984,22,1975 present: The Molecular Revolution (2),Tonegawa, genetic basis of Ab variability,PCR & gene cloning techniques + Mabs.,identification, structure & function of Ig & TCR genes, cell surface ags. & cytokines.,23,1975 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,24,谢谢大家!,
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