1. Immunology Jianzhong Chen, PhD Institute of Immunology Zhejiang University

2. References  何维 主编。《医学免疫学》第二版 ，人民卫生出 版社 2010  金伯泉 主编。《医学免疫学》第五版 人民卫生出 版社 2008  Abbus A K, et al. Cellular and Molecular Immunology. 7th Edition,Elsevier Saunders. 2012  Janeway C A, et al. Immunobiology. 8 th ed. Garland Science Publishing. 2012

3. Content  Introduction of Immunology  Brief History of Immunology

4. Introduction of Immunology

5.  Concept of Immunity  Immune Response  Immune Cells  Tissues and Organs of the Immune System  Immunopathology

6. Immunity 1.Immunity: : Meaning the state of protection from infectious disease. In 430BC, a plaque in Athens, Those who recovered from the plaque would not contact the disease a second time. 2. Agents: microorganisms (viruses, bacteria etc) and their products, foods, chemicals, pollen, tumor cells, etc. 3.Immune system: immune tissues and organs, immune cells, immune molecules 4.Immune response: collective and coordinated response to the introduction of foreign substances. 5.Immunology: study the structure of immune system and its functions.

7. Immune Response  I nnate immune response natural immune response non-specific immune response  Adaptive immune response acquired immune response specific immune response

8. The innate and adaptive immune response CharacteristicsCellsMolecules Innate immunity Responds rapidly No memory No or low specificity Physical barriers Phagocytes (PMNs and macrophages) Natural killer cells Humoral factors Complement Acute phase Proteins Cytokines Adaptive immunity Responds Slowly Memory Highly specific T cells B cells Dendritic cells Antibodies Cytokines Granzymes

9. Innate immunity mechanism of recognition  Pathogen associated molecules patterns(PAMPs ） :LPS,DNA,RNA,Protein  Danger-associated molecular patterns (DAMPS):DNA,HSP  Pattern recognition receptors (PRR): Toll-like receptor(TLR),C-lectin recptor(CLR),RIG-I-Like recptor(RLR),NOD-like Receptor(NLR)

11. Innate Immunity Polly Matzinger

12. Adaptive immune response

13. Links between innate and adaptive immunity

14. Cells of immune system

16. Lymphocytes 1.Lymphocytes (except NK cells) are wholly responsible for the specific immune recognition of pathogens, so they initiate adaptive immune responses. 2.Lymphocytes are derived from bone-marrow stem cells. 3.B lymphocytes develop in the bone marrow. T lymphocytes develop in the thymus.

18. Antigen presenting cells (APC) 1. Dendritic cells (DC): powerful in antigen processing and presentation. 2. Macrophage: powerful in antigen processing and destruction, but low in antigen presentation. Introduction

19. Antigen presenting cells Introduction

20. Natural killer cells (NK) 1. 5-10% of blood lymphocytes, LGL 2. express neither T-cell nor B-cell antigen receptors Introduction

21. Phagocytic cells (Lung) Macrophage Attacking E. coli

22. Phagocytic cells  Monocytes (blood)/Macrophages (tissues) functions: 1. remove particulate antigens 2. take up, process and present antigenic peptides to T cells distribution: Kupffer cells in the liver microglial cells in the brain Introduction

23. Phagocytic cells monocyte neutrophil

24. Phagocytic cells  Polymorphonuclear granulocytes 1.neutrophils; basophils; eosinophils 2.neutrophils are short-lived phagocytic cells multilobed nucleus; 10-20  m 3.neutrophils have a large arsenal of antibiotic proteins granules: lysosomes; lactoferrin

26. Innate immunity mechanism of recognition  Pathogen associated molecules patterns(PAMPs ） :LPS,DNA,RNA,Protein  Danger-associated molecular patterns (DAMPS):DNA,HSP  Pattern recognition receptors (PRR): Toll-like receptor(TLR),C-lectin recptor(CLR),RIG-I-Like recptor(RLR),NOD-like Receptor(NLR)

28. Innate Immunity Polly Matzinger

29. Tissues and organs of the immune system Primary (or central) lymphoid organs bone marrow thymus Secondary (or peripheral) lymphoid organs spleen lymph nodes Mucosal-associated lymphoid tissue (MALT)

30. Mucosal immune system (MIS) 1.non-encapsulated lymphoid tissue in the lamina propria and submucosal areas of the gastrointestinal, respiratory and genitourinary tracts. 2. tonsil, appendix, Peyer ’ s patches 3. B cell IgA IEL Adaptive immune (  T cell) 4. function: local (mucosal) immunity

31. Mucosal-associated lymphoid tissue (MALT)

32. Immunopathology Hypersensitivity - overactive immune response Immunodeficiency - ineffective immune response Autoimmunity - inappropriate reaction to self antigens

33. Brief History of Immunology

34.  1. Empirical Immunology(AD1700-1900)  2. Scientific Immunology(1900-1950s)  3. Modern Immunology(1960s-Present)

35. Documents show that as early as AD 1000, the ancient Chinese custom existed of having children inhale powders made from the crusty skin lesions of patients recovering from smallpox

36. Edward Jenner (1749-1823) Jenner vaccination

37. Ali Maali

38. Why Can we eradicate the smallpox?  No animal reservoir  Lifelong immunity  Subclinical cases rare  One serotype  Effective vaccine  Major commitment by governments

39.  Lious Pasteur (1822~1895).  The genius of Pasteur carried him to the solution of many problems: the spoilage of beers and wines, with the accompanying pasteurization process; the discovery of anaerobic bacteria, virus vaccines, and attenuation of virulence; and studies of spontaneous generation. His studies in immunology have rightly earned him the position as father of the science.

40.  Von Behring (1854~1917) discovered the antitoxin and the principles of antiserum therapy. He established one of the first corporations to product immunologic products.

41.  Robert Koch (1843~1910)  for his investigations and discoveries in relation to tuberculosis"

42.  Elie Metchnikoff (1845~1916) converted his discoveries of phagocytosis into a doctrine that gained many disciples from his coterie of students. He shared the Nobel Prize with Ehrlich in 1908.

43.  Paul Ehrlich (1854~1915).  Selective theories(Paul Ehrlich,1900 ） The binding like the fitting of a lock with key,the side- chain specificity was determined before its exposure to Ag, and the Ag selected the appropriate side-chain receptor.  He shared the Nobel Prize with Metchnikoff in 1908.

44. Clonal selection theory and immune tolerance

45. The clonal selection hypothesis

46.  Rodney R. Porter (1917~1985) shared the Nobel Prize in Physiology and Medicine with Edelman in 1972. Gerald M. Edelman (1929~) was only 43 years of age when he shared the Nobel Prize with Porter in 1972.

47. MHC

48. Monoclonal Ab and

49. Susumu Tonegawa is a Japanese Scientist who won the Nobel Prize for physiology or medicine in 1987 "for his discovery of the genetic principle for generation of antibody diversity" Antibody Diversity

50. Peter C. Doherty Rolf M. Zinkernagel ”for their discoveries concerning the specificity of the cell mediated immune defence”

51. The Nobel Prize in Physiology or Medicine 2011 was divided, one half jointly to Bruce A. Beutler and Jules A. Hoffmann "for their discoveries concerning the activation of innate immunity" and the other half to Ralph M. Steinman "for his discovery of the dendritic cell and its role in adaptive immunity".