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