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Chapter 1 History of Immunology

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1 Chapter 1 History of Immunology

2 Chapter 1 History of Immunology
Introduction Experiential Immunology period Experimental Immunology period Modern Immunology period Immunology act as an independent subject: (In 1971, International Conference of Immunology, 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


6 What disease does this man have?

7 Chinese medical practitioners : variolation

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 immunity In the middle of 19th century R. Koch ----Isolated and cultured bacteria successfully Pasteur ----Infectious diseases were caused by pathogens Robert Koch

12 In 1880, Pasteur ----Anti-cholera live-attenuated vaccine (old culture of Chicken V.cholera) ----Artificial active immunity Louis 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 exotoxin produced by C.diphtheriae The discovery of diphtheriae antitoxin and bactericindins Antitoxin----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 immunity Von 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.

17 Active immunity and passive immunity

18 3. Study on antigen In the early of 20th century,Landsteiner
----Study on antigenic determinant(epitope) ----ABO blood type



21 4. Study on immunochemistry
In 1938,Tiselius and Kabat ----Ab is  globulin In the fifties of 20th century,Porter and Edelmen ----Molecular structure of Ab: 4 peptides

22 Albumin glubulin Total serum Total serum The electrophoresis figure of immune serum

23 5. Study on immune tolerance
No positive response to specific Ag In 1945, Oven found natural immune tolerance In 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 placenta Their 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 clones Clone deletion birth Clone 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 receptor The 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 deletion The 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 selection Forbidden clones can be revival and cause antoimmunity.

34 7. Mechanism of protective immunity
Cell mediated immunity(CMI) ,Metchnikoff: Microorganisms were engulfed and destroyed by phagocytic cells Humoral immunity(HI) ,Ehrlich: Ab in serum played important roles in protective immunity Both 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----Anaphylaxis Pirquet and Shick----Hypersensitivity In 1903,Arthus----Arthus phenomenon In 1906,Pirquet ---- Allergy In 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 system In 1957,Glick Fabricius and Xianguang Zhang ----Chicken without bursa can not produce Ab ----B cell In 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 milstein 3. 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 transduction 5. 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-I MHC- II a2 a3 a1 b1 b2 b2m 肽结合单位 Ig样单位 跨膜单位 Jean Dauset 1916-, Nobel Prize 1980 for study on immunogenetics

40 TCR and BCR

41 6. Study on clinical immunology
Organ transplantation Autoimmune disease Tumor immunology Infectious diseases

42 7. Study on applied immunology
Preparation of monoclonal antibody and genetic engineering antibody Preparation of recombinant cytokines Study on DNA vaccine Study on treatment with immune cells

43 8. New techniques of modern immunology and application
Separation of immune cells Protein analysis technique Phage display technique Preparation of new animal model

44 Reference 1.Roitt. Immunology
2.Abbas AK.Cellular and molecular immunology 3.Lydyard PM. Instant Notes in Immunology 4.陈慰峰.医学免疫学(人民卫生出版社) 5.龚非力.医学免疫学(科学出版社) 6.司传平.医学免疫学应试指南 7.尹丙娇.医学免疫学应试指南

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