1. Introduction and History of Immunology
Lecture 1
Introduction and History of Immunology
Weilin Chen, Ph.D
Institute of immunology, ZJU
Phone:

2.  History of Immunology  Immune system  Innate immunity
 Adaptive immunity
Text book:
Medical Immunology 5th ed（金伯泉）
References:
Natural Review of Immunology
Annual Review of Immunology

3. Immunity
Immunity: refers to all mechanisms used by the body as protection against environmental agents that are foreign to the body.
The term “immunity” was first used in 1775 by Van Sweiten, a Dutch physician, as “immunitas” to describe the effects induced by an early attempt at variolization.

4. Variolation
• To induce immunity deliberately were performed by the Chinese in the 1200 – a technique called variolation • Edward Jenner an English country doctor in 1798, took the scrab from Sarah Nelmes, a milkmaids and inserted into arm of James Phipps, a 8-year old boy. Eight weeks later, James was challenged with the deadly smallpox.

5. Louis Pasteur ( )  
Pasteur called the attenuated strain as “Vaccine”.
The latin word “vacca=cow” in honor of Jenner’s work.
Attenuated vaccines for cholera, anthrax, and rabies
On July 4, 1886, 9-year-old Joseph Meister was bitten repeatedly by a rabid dog， Pasteur treated him with his attenuated rabies vaccine two days later. Meister survived.
Joseph Meister later become a gatekeeper for the Pasteur Institute. In 1940, when he was ordered by the German occupiers to open Pasteur's crypt, Joseph Meister refused and committed suicide!
cholera ['kɑlərə] ['kɔlərə] 1. 名词 [医学] 霍乱
anthrax [.ænθræks] ['ænθræks] 1. 名词 [兽医] 炭疽
rabies ['reɪbiːz] 1. 名词 [u] 狂犬病

6. · Discovered the tubercle bacillus and tuberculin.
Robert Koch ( )
·       German physician; also started to work on Anthrax in 1870's. Identified the spore stage. First time the causative agent of an infectious disease was identified.
·       Discovered the tubercle bacillus and tuberculin.
Detailed tuberculin skin test (DTH).
Awarded 1905 Nobel Prize.

7. Emil Adolf von Behring (1854 – 1917)
A Student of Koch
With Kitasato and Wernike, discovered anti-toxin
for Diphtheria and Tetanus and applied as therapy.
Awarded first Nobel Prize in physiology, 1901
diphtheria [dɪf'θɪrɪə] [dɪf'θɪərɪə] 1. 名词 [医学] 白喉
tetanus ['tεtənəs] 1. 名词 [医] [u] 破伤风

8. · Worked with Koch. Developed anti-toxin (Diphtheria) and hemalysis
Paul Ehrlich (1854 – 1915)
      Developed a series of tissue-staining dyes including that for tubercle bacillus.
·  Worked with Koch. Developed anti-toxin (Diphtheria) and hemalysis
·   Side-chain theory of antibody formation:
"surface receptors bound by lock & key; Ag stimulated receptors"
·   Shared 1908 Nobel Prize with Metchnikoff.

9. Elie Metchnikoff ( )
·   Embryologist studying starfish development.
·   Found phagocytosis. Phagocytes from larva stuck on thorn from a tangerine tree. Later he found a fungal spore attached to a phagocyte of Daphnia. Formed the basis of leukocyte phagocytosis.
·   Birth of cellular immunology
Shared Nobel Prize with Ehrlich in 1908

10. Sir Frank Macfarlane Burnet (1899-1985)
Sir Frank Macfarlane Burnet ( )
·    Important work on influenza. Discovery of an influenza viral enzyme with the specificity for particular forms of neuramic acid. Used today for detection.
Clonal selection theory to explain tolerance
1960 Nobel Prize for the discovery of acquired immunological tolerance. Rejection of donor grafts was due to an immunological reaction and that tolerance can be built up by injections into embryos.
神经氨酸(神經氨酸) neuramic acid;neuraminic acid

11. 1972 Nobel Prize for their discoveries
concerning the chemical structure of antibodies.
Rodney R. Porter
Gerald M. Edelman
1929-

12. BARUJ BENACERRAF
JEAN DAUSSET
GEORGE D. SNELL
Discovered genes that regulate immune responses (Ir gene),
Now known ad the major histocompatibility antigens
1980 Noble prize

13. Niels K. Jerne ( )
·   Antibody avidity maturation
·   Plaque forming assay
·   Pre-existing repertoire (in host DNA) theory helped the formation of clonal selection theory.
·   Host MHC is the driving force for the maturation and selection of T cells in the thymus.
·   **Idiotype network
Nobel Prize, 1984, for theories concerning "the specificity in development and control of the immune system" and the discovery of "the principle for production of monoclonal antibodies."
                               

14. Milstein (b. 1927) and Köhler (1946-1995)
·   Monoclonal antibody
                               

15. Cloning of the Immunoglobulin gene
Susumu Tonegawa (b. 1939)
Cloning of the Immunoglobulin gene
1987 Nobel prize for his discovery of "the genetic principle for generation of antibody diversity".

16. Peter C. Doherty and Rolf M. Zinkernagel
·       Two signals
·        1996 Nobel Prize for their discoveries concerning "the specificity of the cell-mediated immune defense".
                               

17. Why we need to study immunology?

18. New emerging diseases are close to us

20. Resurrection of 1918 Flu From Sequenced Fragments

21. HIV and AIDS

22. Allergy
Graft rejection
Autoimmunity

23. Immune responses Barriers Skin & Mucous membranes
rapidly regenerating surfaces, peristaltic
movement, mucociliary escalator,
vomiting, flow of urine/tears, coughing
Cellular and humoral defences
lysosyme, sebaceous/mucous secretions,
stomach acid, commensal
organisms,complement proteins,
phagocytosis, NK cells
Antibodies, cytokines, T helper cells,
cytotoxic T cells
Invasion
& infection
Innate immunity
Inflammation
Adaptive immunity

24. Immune Responses innate immune response natural immune response
non-specific immune response
adaptive immune response
acquired immune response
specific immune response

26. The innate and adaptive immune response
Characteristics
Cells
Moleculars
Innate immunity
Responds rapidly
No memory
Phagocytes (PMNs and macrophages)
Natural killer cells
Master cells
Dendritic cells
Cytokines
Complement
Acute phase proteins
Adaptive immunity
Slow too start
Highly specific
Memory
T cells
B cells
Antibodies

27. innate immune response
Physiological barriers
skin
mucous membranes
Phagocytosis
polymorphonuclear leukocytes(PMN)
macrophages
Natural killer(NK) cell
cytokines and inflammation

28. Macrophage attacking bacteria
(Lung) Macrophage Attacking E. coli

29. adaptive immune response
The activation of lymphocytes
antigen
TCR(T cell receptor)
BCR(B cell receptor)
Proliferation and differentiation of lymphocytes
B cell----cytokines
T cell----Antigen-TCR;co-stimulatory signal
Effective cell
B cell----Antibody; T cell----CTL
Memory cell

30. adaptive immune response

31. adaptive immune response

32. Immune Response

34. Phagocytic cells Monocytes/Macrophages
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

35. Phagocytic cells
monocyte

36. Phagocytic cells Neutrophils multilobed nucleus; 10-20μm
1.neutrophils are short-lived phagocytic cells
multilobed nucleus; 10-20μm
2.neutrophils have a large arsenal（军火库，兵工厂） of antibiotic protein
granules:lysosomes;lactoferrin;lysozyme

37. Neutrophil

38. Lymphocytes
1.Lymphocytes are wholly完全的 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.

39. B Lymphocytes
⑴ BCR:a surface receptor specific for a particular antigen ⑵ B cells antigen plasma cells secrete antibody ⑶ humoral immunity

40. B Lymphocytes

41. T Lymphocytes
⑴ TCR:T-cell antigen receptor TCRαβ+ >95% TCRγδ+ 1–5% ⑵ CTL,cytotoxic T cells regulatory T cells helper T cells,Th ⑶ CMI,cell mediated immunity

42. Antigen presenting cells
Macrophage: antigen processing high antigen presenting low Dentritic cell(DC):antigen presenting high

43. Antigen presenting cells

44. Natural killer cells(NK)
⑴ 15% of blood lymphocytes ⑵ express neither T-cell nor B-cell antigen receptors

45. Components of blood

46. Tissues and organs of the immune system
Primary lymphoid organs the bone marrow the thymus gland Secondary lymphoid organs the spleen lymph nodes Mucosal-associated lymphoid tissue

47. Functions of lymphoid organs

48. Bone marrow the place in which proliferation of HSC take place
the place in which development and maturation of B cells occur
3. The lymphoid progenitor cells are transported by circulating blood to the thymus and differentiate into fuctional T lymphocytes

49. Thymus
1.Cells:thymic stromal cells(TSC) thymocytes T cell (αβ+ ) monocytes,macrophage,TDC 2.Structure:cortex---immature thymocytes madulla---mature thymocytes Mø,TDC 3.Function:It is the site of T cell maturation; It determines the specificity of the TCR expressed on the T cells released to periphery

51. thymus gland

53. spleen
1. adult spleen:13*8cm g 2. the white pulp:lymphoid cells the red pulp venous sinuses cellular cords 3.function:a reservoiv for platelets, erythrocytes and granulocytes; destroy the Ag,aged platelets

54. spleen

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56. lymph node Human:2-10mm in diameter round and kidney shaped
Consists of : B-cell area(cortex)
T-cell area(paracortex)
central medulla

58. lymph node

60. Mucosal-associated lymphoid tissue(MALT)
1.non-encapsulated lymphoid tissue 2.in the lamina propria and submucosal areas of the gastrointestinal,respiratory and genitourinary tracts. 3.tonsil, appendix, Peyer’s patches 4.B cell IgA IEL Adaptive immune

61. Mucosal-associated lymphoid tissue(MALT)

62. Peyer’s patches

63. M cell

64. Lymphocyte recirculation
Lymphocytes leave the blood via high-walled endothelium of the post-capillary venules
Lymphocyte trafficking exposes antigen to a large number of lymphocytes

66. Lymphocyte recirculation