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Chapter 1 History of Immunology

Chapter 1 History of Immunology. The position of Immunology in life science. Immunology is one of three pioneer subjects in life science Three pioneer subjects : Molecular Biology Neurobiology Immunology.

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Chapter 1 History of Immunology

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  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. 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 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% 2004全球生物技术药物 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 • 《Immunology》 Chief editor： Roitt • Cellular and molecular Immunology Chief editor: Abbas and Litchman

  7. 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

  8. 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

  9. 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

  10. 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

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

  12. SARS

  13. 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. 17-18'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 (1979.12)

  14. Chinese medical practitioners : variolation (人痘）

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

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

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

  18. (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(1822-1895) RobertKoch

  19. (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

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

  21. (II)Discovery of antibody（抗体）and passive immunity（1） 1. Discovery of antibody 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 produceantibody

  22. (II) Discovery of antibody and passive immunity-22.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

  23. Active immunity and passive immunity • Immunityis 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

  24. (II) Discovery of antibody and passive immunity-3 3. Recognition aboutStructure 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 antibodyis composed of two identical heavy chains and two identical light chains

  25. 4.Hypothesis for the formation of antibodiesTemplates 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 1984Burnett Got Nobel prize in1960，In physiology and medicine (II) Discovery of antibody and passive immunity-4

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

  27. Clonal selection theory （1）Each lymphocyte bears a single type of receptor with a unique specificity （2）lymphocyte bearing receptors specific for ubiquitous self moleculesare 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

  28. (III) Mechanism of immunity Humoral immunity-----Paul Erlich antibody in blood binds to antigen Cellular immunity----- Elie Metchnikoff Chicken phagocytes in blood phagocytized anthracoides

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

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

  31. 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）

  32. 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

  33. 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

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

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

  36. 3. Pathway of programmed cell death

  37. 4. Cytokine andadhesion molecules （细胞因子） （黏附分子）

  38. Cytokine andadhesive 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.

  39. 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）

  40. Polyclonal antibody: a mixture of Abs with different specificities and affinities • Monoclonal antibodyAbs 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

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

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

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

  44. 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

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