1、1The History of ImmunologyJr.Hons.Immunology B.Sc.D.I.Stott“He who ignores history is doomed to repeat it.”2Stages 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.
2、R.The molecular revolution present3Descriptive 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-immune4Early Attempts at Immunisation Mithrad
3、ates 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.5A Smallpox Victim6Immunisation against Smallpox(1)Variolation Early 18th C.:Lady Mary Wortley Montagu(wife
4、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 popula
5、r.7Immunisation 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.Medawar tolerance to skin allograftsCellular Theory:Elie Metchnikoff Phagocytes in starfish larvae sur
6、round a splinter;phagocytosis&digestion of bacteria by Ms&polymorphs Phagocytic Theory(innate immunity).Passive tf.Causes of disease unknown until 19th C.Chinese:dried matter from pustules inserted in nostrils.Causes of disease unknown until 19th C.20th C:How are Abs.Edward Jenner inoculating James
7、Phipps with cowpoxImmunisation against Smallpox(2)VaccinationRole of T-cells:Th cells(T-B cell cooperation),Tc cells(kill virus infected cells).Repeated with 6 more criminals+5 orphans.Abs as proteinsInoculated 7 subjects with cowpox.Edward Jenner inoculating James Phipps with cowpox20th C:How are A
8、bs.stimulate the phagocytes”.Abs as proteinsof immune serum protection=1st immunotherapy.Instructive Theoriesmade?Selective v.8Edward Jenner inoculating James Phipps with cowpox910Immunisation against Smallpox(3)WHO Programme 1978:WHO Programme completed.Smallpox completely eradicated worldwide.1119
9、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.12Wars of The Cells and Antibodies Cellular Theory:Elie Metchnikoff Phagocytes in starfish larvae sur
10、round 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)Showed serum from immunised animals kills bacteria.13Ilya Metchnikoff14Humoral Immunity Bordet
11、discovered complement.Behring&Kitasato immunity to diphtheria&tetanus due to Abs.v.toxins.Passive tf.of immune serum protection=1st immunotherapy.1516Wars of The Cells and Antibodies:Truce Sir Almoth Wright&Douglas-Opsonisation of bacteria by Abs.Attempted fusion of Cellular and Humoral Theories “Si
12、r Almost Right”.Little progress in cellular immunology for 50 years(unfashionable).1720th 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 Selectio
13、n Theory.18Attempted fusion of Cellular and Humoral Theories “Sir Almost Right”.Sir MacFarlane Burnet Clonal Selection Theory.Abs as proteinsPlagues&pandemics,esp.Causes of disease unknown until 19th C.made?Selective v.Little progress in cellular immunology for 50 years(unfashionable).):people who r
14、ecovered-immuneGenetic manipulation:Gene K.20th C:How are Abs.Early experiments:Bacteria cause diseaseHumoral Theory:Koch,Ehrlich et al.chicken cholera,anthrax,rabies.The History of ImmunologyNobel Prize 1984):people who recovered-immunePCR&gene cloning techniques+Mabs.,signalling pathways etc.Repea
15、ted with 6 more criminals+5 orphans.Smallpox completely eradicated worldwide.bound to MHC19Chemical approach to Abs.&Ags.Landsteiner:Specificity&diversity;blood group ags.Abs as proteins Porter&Edelman:1st Description of structure of IgG20R.R.Porter21Return to Cellular Theories(In parallel with stud
16、ies 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 MHC221975 present:The Molecular Revolution(1)K
17、hler&Milstein:Monoclonal AbsNobel Prize 1984231975 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.241975 present:The Molecular Revolution(3)Genetic manipulation
18、: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 therapy25A Smallpox Victim26Edward Jenner inoculating James Phipps with cowpox272820th C:How are Abs.ma
19、de?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.Edward Jenner inoculating James Phipps with cowpoxReturn to Cellular TheoriesThe History of Immun
20、ologyCauses of disease unknown until 19th C.Behring&Kitasato immunity to diphtheria&tetanus due to Abs.Little progress in cellular immunology for 50 years(unfashionable).20th C:How are Abs.Plagues&pandemics,esp.George I pardoned 7 criminals:inoculated;1 lay with smallpox victim every night to end.19
21、75 present:The Molecular Revolution(1)Immunisation against Smallpox(3)WHO ProgrammeCellular Theory:Elie Metchnikoff Phagocytes in starfish larvae surround a splinter;phagocytosis&digestion of bacteria by Ms&polymorphs Phagocytic Theory(innate immunity).20th C:How are Abs.1975 present:The Molecular R
22、evolution(3)The History of ImmunologyCauses of disease unknown until 19th C.bound to MHCShaw,“The Doctors Dilemma”:“.Plagues&pandemics,esp.The History of ImmunologyRepeated with 6 more criminals+5 orphans.Causes of disease unknown until 19th C.1975 present:The Molecular Revolution(3)Sir MacFarlane B
23、urnet Clonal Selection Theory.Porter&Edelman:1st Description of structure of IgG1975 present:The Molecular Revolution(2)and transgenic mice enable study of effects of molecular components of I.Genetic manipulation:Gene K.:Bacteria cause diseaseHumoral ImmunityPorter&Edelman:1st Description of struct
24、ure of IgGSir MacFarlane Burnet Clonal Selection Theory.Immunology B.Return to Cellular Theories identification,structure&function of Ig&TCR genes,cell surface ags.Khler&Milstein:Monoclonal Abs):people who recovered-immuneEhrlichs Side Chain Theory(selective)of immune serum protection=1st immunother
25、apy.1978:WHO Programme completed.and transgenic mice enable study of effects of molecular components of I.Descriptive Early Period29R.R.Porterstimulate the phagocytes”.Repeated with 6 more criminals+5 orphans.and transgenic mice enable study of effects of molecular components of I.Edward Jenner inoc
26、ulating James Phipps with cowpoxImmunisation against Smallpox(3)WHO ProgrammeImmunology B.made?Selective v.):people who recovered-immuneCauses of disease unknown until 19th C.Causes of disease unknown until 19th C.A Smallpox VictimGeorge I pardoned 7 criminals:inoculated;1 lay with smallpox victim e
27、very night to end.Abs as proteinsPauling-Instructive TheoryCellular Theory:Elie Metchnikoff Phagocytes in starfish larvae surround a splinter;phagocytosis&digestion of bacteria by Ms&polymorphs Phagocytic Theory(innate immunity).Then 2 daughters of Prince&Princess of Wales inoculated,hence became po
28、pular.of immune serum protection=1st immunotherapy.1975 present:The Molecular Revolution(3)Humoral immunity cannot explain graft rejection,tolerance,immunity to viruses.Immunisation against Smallpox(1)VariolationCellular Theory:Elie Metchnikoff Phagocytes in starfish larvae surround a splinter;phago
29、cytosis&digestion of bacteria by Ms&polymorphs Phagocytic Theory(innate immunity).):people who recovered-immunePlagues&pandemics,esp.Passive tf.Causes of disease unknown until 19th C.Early Attempts at Immunisationmade?Selective v.Thucydides(5thC.1975 present:The Molecular Revolution(2)identification
30、,structure&function of Ig&TCR genes,cell surface ags.Showed serum from immunised animals kills bacteria.of immune serum protection=1st immunotherapy.Behring&Kitasato immunity to diphtheria&tetanus due to Abs.Medawar tolerance to skin allograftsbound to MHC1975 present:The Molecular Revolution(3)Earl
31、y experiments:Bacteria cause diseaseZinkernagel&Doherty Tc recognise ag.The History of ImmunologyPCR&gene cloning techniques+Mabs.Immunisation against Smallpox:-20th C:How are Abs.Showed serum from immunised animals kills bacteria.301975 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.
