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The History of Immunology

The History of Immunology. Jr. Hons. Immunology B.Sc. D. I. Stott. “He who ignores history is doomed to repeat it.”. Stages of Immunology. Descriptive early period Early attempts at vaccination: Smallpox Early experiments: Bacteria cause disease Humoral v. cellular immunity

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The History of Immunology

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  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 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

  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 • 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.

  5. A Smallpox Victim

  6. Immunisation against Smallpox (1) Variolation • Early 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 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.

  7. Immunisation against Smallpox (2) Vaccination • End of 18th C.: Edward Jenner • Inoculated 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. Immunisation against Smallpox (3) WHO Programme • 1978: WHO Programme completed. Smallpox completely eradicated worldwide.

  10. 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.

  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 Doctor’s 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 = 1st immunotherapy. 

  14. 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).

  15. 20th C: How are Abs. made? Selective v. Instructive Theories • Are Abs pre-made (selective) or “moulded” by ag (instructive)? • Ehrlich’s Side Chain Theory (selective) • Pauling - Instructive Theory • Sir MacFarlane Burnet – Clonal Selection Theory.

  16. Chemical approach to Abs. & Ags. • Landsteiner: Specificity & diversity; blood group ags. • Abs as proteins • Porter & Edelman: 1st Description of structure of IgG

  17. R. R. Porter

  18. 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

  19. 1975 – present: The Molecular Revolution (1) • Köhler & Milstein: Monoclonal Abs Nobel Prize 1984

  20. 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.

  21. 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 & immunotherapy; recombinant & DNA vaccines; gene therapy

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