1. Chapter 1
History of Immunology

2. The position of Immunology in life science
Immunology is one of three pioneer subjects in life science
Three pioneer subjects:
Molecular Biology
Neurobiology
Immunology

3. 免疫学的发展带动了生命科学的基础研究 Immunology promotes basic research in life science 自然科学影响因子最高的杂志—2012年 IF=52.761

4. 免疫学的发展推动了临床医学各科的发展 (The immunology promotes the development of clinical subjects)
免疫与肿瘤(Immunity and tumor)
免疫与感染性疾病( Immunity and infectious diseases )
免疫与移植(immunity and transplantation
免疫与自身免疫性疾病( immunity and autoimmune diseases)

5. (The immunology promotes the production of biomedicine )
免疫的发展带动生物制药工业的发展
(The immunology promotes the production of biomedicine )
免疫相关产品是生物技术产业中的支柱
2004全球生物技术药物
2003年全球生物技术药品市场达到600亿美元，
市场占有率15%以上的5种产品中免疫相关产品3个:
EPO:28%
干扰素:15%
集落刺激因子:15%
80%免疫相关

6. Reference textbooks 《医学免疫学》十二五规划双语教材， 主编：孙汶生 出版社：高等教育
主编：孙汶生 出版社：高等教育
《Immunology》 Chief editor： Roitt
Cellular and molecular Immunology
Chief editor: Abbas and Litchman

8. Medical immunology Pert I. Introduction of Immunology
Part II. Immune molecules
Part III. Immune cells and immune responses
Part IV. Clinical Immunity and its application

9. Part I Introduction of immunology
Chapter I. History of Immunology
Chapter II. Modern Immunology and its
development strategies
Chapter III. General Introduction of immune system
Chapter IV. Antigens

10. Chapter 1 History of Immunology
Immunology was established with process that
human being fought against infectious diseases.
Period of Experience Immunology
Period of Experimental Immunology
Period of Modern Immunology

11. I. Period of Experience Immunology (16-19‘s) ----Formation of immunity conception
The term immunity is derived from the Latin word immunitas, which referred to the protection from legal prosecution offered to Roma senators
The immunity was used first time to refer to an infection that was called” plague” ( 瘟疫）during the fifth century BC

13. The individual who has suffered from smallpox do not worry about smallpox again
Mortality of smallpox is 30%

14. SARS

15. The formation of immunity conception
Human smallpox (天花） vaccine ：variolation（人痘）
to prevent smallpox used by Chinese ---first time using conception of immunity to prevent disease 's Ming Dynasty
 Cowpox（牛痘） vaccine (1798 )--- Edward Jenner’s successful vaccination against smallpox
Edward Jenner: an English physician
Smallpox was first disease that had been eradicated worldwide by a program of vaccination ( )

16. Chinese medical practitioners : variolation (人痘）

17. exposure to cowpox can prevents smallpox---- vaccination（1796）
Edawar Jennar
occupational doctor
exposure to cowpox can prevents smallpox---- vaccination（1796）
vaccine

18. They should be vaccinated first
Why do they not want to play with my kids?

19. II. Period of Experimental Immunology
Late period of 19's ---middle period of 20's
Establishment and development of immunology

20. (I) Discovery of pathogen and Active immunization（1）
l . discovery of Pathogen
Louis Paster: anthracoides（炭疽杆菌)
Koch: tubercle bacillus （结核杆菌）
Louis Pasteur( )
Robert Koch

21. (I) Discovery of pathogen and Active immunity（2）
2. Vaccination and Active immunization
Vaccination : (种痘，接种疫苗,预防接种）
Attenuated vaccine ( 减毒疫苗):Louis Pasteur
Anthrax（炭疽） vaccine
chicken cholera ( 鸡霍乱) Vaccine
A rabies ( 狂犬病）vaccine

22. Louis Pasteur(1822-1895) Louis Pasteur Anti-cholera :
Vaccination and active immunization
Louis Pasteur
Anti-cholera :
1878, old attenuated culture of chicken cholera
---- vaccine
Anti-anthrax
rabies vaccine
(attenuated vaccine)
Louis Pasteur( )

23. (II) Discovery of antibody（抗体）and passive immunity（1）
1888: Roux and Yersin discovered that exotoxin ( 外毒素） produced by C. diphtheriae （白喉杆菌） caused
diphtheria
1889. Von Behring and Kitasato discovered bactericidins
( 杀菌素） or antitoxin(抗毒素）in serum of patient
with diphtheria--- first antibody discovered
1890 Von Behring and Kitasato used diphtheriae antitoxin to
treat patient with diphtheria
Antigen: substance that stimulates individual to produce antibody

24. (II) Discovery of antibody and passive immunity-2 2
(II) Discovery of antibody and passive immunity-2 2.passive immunization
1888 exotoxin produced by C.Diphtheriae
1891 Diphtheria antitoxin
( Behring and Kitasato)
passive immunity
Humoral immunity (Ehrlich)
. antiserum , antibody (Ab)
. antigen (Ag)
. serology
Ehrlich

25. Active immunity and passive immunity
Immunity is the protection from diseases and more responsible for infection diseases.
immunity possesses specificity
Active immunity: The form of immunity that is induced by exposure to a foreign antigen, in which the immunized individual plays an active role in responding to the antigen
Passive immunity :The form of immunity that is established in one individual by transfer of antibodies or lymphocytes from another individual who is immune to that antigen

26. (II) Discovery of antibody and passive immunity-3
3. Recognition about Structure
of antibody and its specificity
binding to antigen
Antibody：a type of glycoprotein molecule, also called immunoglobulin (Ig) , produced by B cells that bind antigens .often with a high degree of specificity
The basic structural unit of antibody is composed of two identical heavy chains and two identical light chains

27. (II) Discovery of antibody and passive immunity-4
4.Hypothesis for the formation of antibodies Templates postulate (lock and key) 模板假说 Natural selection postulate(1955,Jerne) 自然选择假说 Clonal selection theory :  1957, Burnet 克隆选择学说: (cells as center)     Jerne got it in Burnett Got Nobel prize in1960， In physiology and medicine

28. Burnet Clonal selection theory
Various clones
Clone deletion
birth
Clone selection
Clone expansion

29. Clonal selection theory
（1）Each lymphocyte bears a single type of receptor with
a unique specificity
（2）lymphocyte bearing receptors specific for ubiquitous self
molecules are deleted in early stage of lymphoid cell
development and are therefore absent from the repertoire
of mature
（3）Interaction between a foreign molecule and specific
receptor with high affinity leads to lymphocyte activation
（4）The differentiated effective cells derived from an activated
lymphocyte will bear receptor of identical specificity

31. (III) Mechanism of immunity
Humoral immunity-----Paul Erlich
antibody in blood binds to antigen
Cellular immunity----- Elie Metchnikoff
Chicken phagocytes in blood
phagocytized anthracoides
Got Nobel prize in1908
In physiology and medicine

32. chimeras (IV) Immune tolerance dizygotic twins 异卵双生 placenta
placenta
dizygotic twins
异卵双生
chimeras
, Owen observed phenomena of natural immune tolerance
1953, Medawar confirmed immune tolerance by experiment

34. Immunologic tolerance is defined as unresponsiveness to an antigen that is induced by prior exposure to that antigen.

35. V. Immunopathology Anaphylaxis（过敏反应）or hypersensitivity：超敏反应
 graft rejection（移植排斥）
autoimmune disease（自身免疫性疾病）
Immunodeficiency（免疫缺陷）

36. New conception of Immunity
In a broader sense , immunity is refers to the ability to respond to foreign substances (antigen), including microbes , as well as to macromolecules such as proteins and polysaccharides, regardless of the physiologic or pathologic consequence of such a reaction to foreign substance

37. Chapter 1 History of Immunology
Immunology was established with process that
human being fought against infectious diseases.
Period of Experience Immunology
Period of Experimental Immunology
Period of Modern Immunology

38.  1. Diversity (多样性）of antigen receptor

39. 2. Pathway of signal transduction（信号传导 ）

40. 3. Pathway of programmed cell death 

41. 4. Cytokine and  adhesion molecules
（细胞因子） （黏附分子）

42. Cytokine and adhesive molecules
Cytokines: a group of low molecule weight proteins with high activity and multiple functions that are secreted by many different kinds of cells and that mediate immune response and inflammatory reaction
Adhesive molecules:
The cell surface molecules whose function is to promote adhesive interactions with other cells or the extracellular matrix and play crucial roles in cell interaction, recognition , activation and migration Leukocytes express various types of adhesion molecules, such as selectins, integrins, and members of the Ig superfamily, cadherin.

43. Polyclonal antibody （多克隆抗体） monoclonal antibody （单克隆抗体）
5. development of technique producing Ab
Polyclonal antibody （多克隆抗体）
monoclonal antibody （单克隆抗体）
gene engineering antibody（基因工程抗体）

44. Polyclonal antibody: a mixture of Abs with different specificities and affinities
Monoclonal antibody Abs produced by single B cell clone (or one hybridoma clone ) possess same structure and specificity.
gene engineering antibody:Abs prepared by the method of gene recombination

45. Established monoclonal Ab product methods in 19745 and got Nobel Prize in 1984
Georges J.F. Köhler
César Milstein

47. Gene engineering Ab：Abs prepared by the method of gene recombination

48. 6. transgenic animal（转基因动物）and gene knockout animal（基因敲除动物）

50. 2007年诺贝尔医学奖获得者 Martin J. Evans ，英国 Oliver Smithies ，美国
Mario R. Capecchi ，美国

51. This year's Nobel Laureates have made a series of ground-breaking discoveries concerning embryonic stem cells and DNA recombination in mammals.
Their discoveries led to the creation of an immensely powerful technology referred to as gene targeting in mice.
It is now being applied to virtually all areas of biomedicine – from basic research to the development of new therapies
Gene targeting is often used to inactivate single genes. Such gene "knockout" experiments have elucidated the roles of numerous genes in embryonic development, adult physiology, aging and disease.
To date, more than ten thousand mouse genes (approximately half of the genes in the mammalian genome) have been knocked out.
Ongoing international efforts will make "knockout mice" for all genes available within the near future.

52. 7.MHC ( major histocompatibility complex, 组织相容性复合体） and finding of MHC restriction (MHC 限制性)
Doherty and Zinkernagel brought forward MHC restriction theory in 1974 and got Noble Prize in 1996

53. The Nobel Prize in Physiology or Medicine 1996
"for their discoveries concerning the specificity of the cell mediated immune defense"
Peter C. Doherty (1940)
1/2 of the prize
Australia St. Jude Children's Research Hospital Memphis, TN, USA
Rolf M. Zinkernagel (1944)
1/2 of the prize
Switzerland , University of Zurich, Institute of Experimental Immunology Zurich, Switzerland