2 Chapter 1 History of Immunology IntroductionExperiential Immunology periodExperimental Immunology periodModern Immunology periodImmunology act as an independent subject:(In 1971, International Conference ofImmunology, in USA )
3 I. Experiential Immunology period (the 17th century- the middle of 19th century) In ancient times,many serious infection diseases,such as smallpox,plague and cholera etc,caused inumerable people dead.
4 Do you know ? Plague !!! --- Black Death Disease
8 Edward Jennar ----An English physician He discovered that cowpox vaccination protected against smallpox in 1796
9 Vaccine: A preparation of microbial antigen,often combined with adjuvants,that is administered to individuals to induce protective immunity against microbial infections.Vaccination: A general term for immunization against infectious diseases,orginally derived from immunization against smallpox which uses the Vaccinia virus.
10 They should be vaccinated first Why do they not want to play with my kids?
11 II. Experimental Immunology period (the middle of 19th century-the middle of 20th century) 1.Active immunityIn the middle of 19th centuryR. Koch----Isolated and cultured bacteria successfullyPasteur----Infectious diseases were causedby pathogensRobert Koch
12 In 1880, Pasteur----Anti-cholera live-attenuatedvaccine(old culture of Chicken V.cholera)----Artificial active immunityLouis Pasteur( )
13 Active immunity:The form of adaptive immunity that is induced by exposure to a foreign antigen and in which the immunized individual plays an active role in responding to the antigen.
14 2. Passive immunity In the late eighties of 19th century Roux and Yersin----Diphtheria was caused by exotoxinproduced by C.diphtheriaeThe discovery of diphtheriae antitoxinand bactericindinsAntitoxin----Antibody (Ab)Exotoxin----Antigen (Ag)
15 Study on reaction of Ag and Ab in vitro ----Serology In 1890,Von Behring and Kitasato----diphtheriae antitoxin was applied in treatment of Diphtheria---- Artificial passive immunityVon Behring
16 Passive immunity:The form of immunity to an antigen that is established in one individual by transfer of antibody or lymphocytes from another individual who is immune to that antigen.
21 4. Study on immunochemistry In 1938,Tiselius and Kabat----Ab is globulinIn the fifties of 20th century,Porter and Edelmen----Molecular structure of Ab:4 peptides
22 AlbuminglubulinTotal serumTotal serumThe electrophoresis figure of immune serum
23 5. Study on immune tolerance No positive response to specific AgIn 1945, Oven found natural immune toleranceIn 1953,Medawar set up animal model of acquired immune tolerance in newborn period.
24 cattle of dizygotic twin Need for tissue and organ graft drove the curiosity to understand the mechanisms of tolerance. The observations a zoologist, Owens, that Dizygotic bovine twins could accept grafts from each other but their siblings from other pregnancies could not tolerate such grafts led Medawar to perform a series of experiments to induce tolerance in mice.
25 Calf of dizygotic twins Commonly use one placentaTheir blood types are different and form chimeras
27 6. Hypothesis for Ab formation Templates postulate (1930,Breinl and Haurowitz)Variable folding postulate (1940,Pauling)Natural selection postulate (1955,Jerne)Clonal selection theory (1959, Burnet)Clone: a group cells that stem from identical cell
28 Various clonesClone deletionbirthClone selection
29 Clonal selection theory (1)There are various lymphocyte clones in our body, each of them bears a unique type of Ag receptor which can recognize Ag specifically.
30 Clonal selection theory (2)The clones of lymphocytes that can recognize self-Ags will be destroyed or learn to tolerance to self Ags (forbidden clones) at the early stage of their development.----clone deletion
31 Clonal selection theory (3)The clones of lymphocytes that can be interacted with corresponding Ag will be selected and lead to activation, proliferation , produce Ab and specific memory cells.---- clone selection
32 Clonal selection theory (4) Forbidden clones can be revival and cause antoimmunity.
33 Clonal selection theory There are various lymphocyte clones, each clone only bears a unique type of Ag receptorThe clones of lymphocyte that can recognize self-Ags will be destroyed or learn to tolerance to self Ags (forbidden clones) at the early stage of their development---clone deletionThe clones of lymphocytes that can be interacted with corresponding Ag (by Ag receptors ) can be selected and lead to activation, proliferation , produce Ab and specific memory cells---clone selectionForbidden clones can be revival and cause antoimmunity.
34 7. Mechanism of protective immunity Cell mediated immunity(CMI) ,Metchnikoff:Microorganisms were engulfed and destroyedby phagocytic cellsHumoral immunity(HI) ,Ehrlich:Ab in serum played important roles in protective immunityBoth HI and CMI were very important for protective immunity,Ab in serum could promote the phagocytosis of phagocytic cells, Wright & Dauglas
35 8. Study on immune-pathology & immune disease In 1902,Richet and Portier----AnaphylaxisPirquet and Shick----HypersensitivityIn 1903,Arthus----Arthus phenomenonIn 1906,Pirquet ---- AllergyIn 1907,Donath and Landsteiner----Autoantibody cause autoimmune disease
36 III. Modern Immunology period (the middle of 20th century-the 21th century) 1. Study on immune systemIn 1957,Glick Fabricius and Xianguang Zhang----Chicken without bursa can not produce Ab----B cellIn 1961,Good and Miller----cell mediated immune of new born mice whose thymus were taken away are defective----T cell
38 2. Study on monoclonal antibody 3. Study on immune genetics ----In 1975,Kohler and milstein3. Study on immune genetics----In 1978,genetic control of antibody diversity----Discovery of accurate mechanism of immune response on gene level (MHC, TCR , BCR)4. Study on molecular mechanism of T/B lymphocyte activation and signal transduction5. Study on effective mechanism of immune cells
39 MHC 分子 —— 处理并展示抗原内在信息的“播放系统” MHC-IMHC- IIa2a3a1b1b2b2m肽结合单位Ig样单位跨膜单位Jean Dauset 1916-, Nobel Prize 1980 for study on immunogenetics