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 period Early attempts at vaccination: Smallpox Early experiments: Bacteria cause disease Humoral v. cellular immunity Selective v. instructive

2、theories of I.R. The molecular revolution present,3,Descriptive Early Period,Plagues 1 lay with smallpox victim every night to end. All recovered. Repeated with 6 more criminals + 5 orphans. Then 2 daughters of Prince phagocytosis & digestion of bacteria by Ms & polymorphs Phagocytic Theory (innate

3、immunity). G.B. Shaw, “The Doctors Dilemma”: “.stimulate the phagocytes”. Humoral Theory: Koch, Ehrlich et al. (Berlin) Showed serum from immunised animals kills bacteria.,13,Ilya Metchnikoff,14,Humoral Immunity,Bordet discovered complement. Behring & Kitasato immunity to diphtheria & tetanus due to

4、 Abs. v. toxins. Passive tf. of immune serum protection = 1st immunotherapy.,15,16,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 5

5、0 years (unfashionable).,17,20th 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.,18,19,Chemical approach to Abs. &

6、 Ags.,Landsteiner: Specificity blood group ags. Abs as proteins Porter & Edelman: 1st Description of structure of IgG,20,R. R. Porter,21,Return to Cellular Theories,(In parallel with studies of Abs.) Humoral immunity cannot explain graft rejection, tolerance, immunity to viruses. Medawar tolerance t

7、o 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,22,1975 present: The Molecular Revolution (1),Khler & Milstein: Monoclonal Abs,Nobel Prize 1984,23,1975 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.,24,1975 present: The Molecular Revolution (3),Genetic manipulation: Gene K.O. and transgenic mice enable study o