1. Overview of Immunology Organs and tissues Cells Molecules － Antibodies － Complement － Cytokines － MHC Components of IS Functions of IS Pathology of IR * IS: Immune system IR: Immune response Applications Prevention Diagnosis Therapy Antigen (Ag) Immune Responses Control mechanisms Hypersensitivity Autoimmune disease Immunodeficiency Tumor Transplantation rejection

2. Consequences of IR Physiology Immunologic defense Immunologic homeostasis Immunologic surveillance Pathology Hypersensitivity Immunodificiency Autoimmune diseases Tumor immunology Transplantation rejection

3. Overview of Immunology Organs and tissues Cells Molecules － Antibodies － Complement － Cytokines － MHC molecules Antigen (Ag) Immune Responses Control mechanisms Hypersensitivity Autoimmune disease Immunodeficiency Tumor immunology Transplantation Components of IS Functions of ISPathology of IR * IS: Immune system IR: Immune response

4. Components of IS -- Organs and tissues Questions: 1.Which organs belong to the immune system? 2. Describe the functions of bone marrow and thymus. 3. What are the functions of secondary lymphoid organs? 4. Terms: MALT—IS / Location / function

5. Components of IS -- Organs and tissues Questions: Describe the mature T cell properties in peripheral lymphoid organs from the functions of thymus. Functions of thymus: -- 4 分 Positive selection Negative selection Mature T cell properties: -- 4 分 Recognition: TCR / MHC + Ag(no-self) Classification: CD4 / CD8

7. — — Bone Marrow Primary source of pluripotent stem cells All haemopoietic cells Place for B cell maturation — — Thymus Place for T cell maturation Primary Lymphoid Organs (Central Lymphoid Organs)

8. Cells of IS are produced from haemopoietic stem cells (HSC) in BM. Stromal cells (epithelial cells, fibroblast, macrophage) is required for the differentiation of a particular lineage. Cytokines( CSF) produced from stromal cells provide the local environment for the hematopoiesis. Primary Lymphoid Organs-- Bone Marrow

9. Large numbers of functionally antigen specific T cells are matured in thymus. Each of T cells has only one specificity. T cells are selected using their receptors ( positive and negative selection) Primary Lymphoid Organs -- Thymus

11. Lymph nodes Place of immune response to pathogen entering the tissues Spleen Place of immune response to blood borne infections MALT Place of immune response to mucosal surfaces Secondary Lymphoid Organs

12. Lymph nodes - Situated alone lymphatic vessels (p30) - Filter of the lymph - Contain T/B lymphocytes and phagocytes (p29) - Place of immune response to pathogen entering the tissues

13. Spleen -- Situated on the left side of the body below the diaphragm -- Filter of the blood -- Contain T/B lymphocytes and phagocytes -- Place of immune response to pathogen entering the blood

14. Overview of Immunology Organs and tissues Cells Molecules － Antibodies － Complement － Cytokines － MHC molecules Antigen (Ag) Immune Responses Control mechanisms Hypersensitivity Autoimmune disease Immunodeficiency Tumor immunology Transplantation Components of IS Functions of ISPathology of IR * IS: Immune system IR: Immune response

15. Components of IS -- Cells Questions: 1. Which cells belong to the immune system? 2. The functions of mononuclear phagocytes are….? 3. Try to explain the classification and function of lymphocytes.

16. The cells of immune system recognize antigens by their receptors, please explain how the cells of followings recognize target antigens: Macrophage: PRR -- 2 分 NK cell: KIR/ KAR-- 2 分 T cells:TCR-- 2 分 B cells:BCR-- 2 分

17. 4. Terms: CD : Marker / identification by mAb / function TCR : Location / structure / function BCR : Location / structure / function PRR : Location / functions KIR : Location / functions KAR : Location / functions

18. — — Mononuclear phagocyte system Monocyte Macrophage Dendritic Cells — — Granulocytes Neutrophils Basophils Eosinophils — — Lymphocytes T lymphocyte B lymphocyte NK (Natural killer cells) Cells of Immune System-Classification

19. Ag DCs Th1 Tc B Ab PMN NK Th2 Complement Functions in Immune Response (IR) Targetcells MHCCK MHCCK CKs CKs

20. — — Phagocytosis — — Antigen presentation — — Cytokine secretion Mononuclear Phagocyte System

21. — — T lymphocyte — — B lymphocyte — — Natural killer cells (NK) Lymphocytes T H1 T H2

22. Infected cells Virus Bacterium IL-1 Perforin Granzymes TNFa/TNFb Killing Cellular immunity BCR Antibody Neutralizing Complement activating NK ADCC Mq Phagocytosis MAC PMN Lysis C3b C3a/C5a Humoral immunity

23. TH (CD4 + CD3 + ) ¹ ¹TH1: Help Tc and macrophages by secretion of IFN/γ/IL-2 ¹ ¹TH2 ： Help B cells by secration of IL-4, IL-5,IL-6 TC (CD8 + CD3 + ) ¹ ¹Killing of target cells by releasing perforin and granzymes Functions of T cells

24.   Antibody production Functions of B cells

25. Antibody Production by B cell Th2

26. NK

28. — — Neutrophils — — Basophils — — Eosinophils Granulocytes

29. Overview of Immunology Organs and tissues Cells Molecules － Antibodies － Complement － Cytokines － MHC molecules Antigen (Ag) Immune Responses Control mechanisms Hypersensitivity Autoimmune disease Immunodeficiency Tumor immunology Transplantation Components of IS Functions of ISPathology of IR * IS: Immune system IR: Immune response

30. Components of IS -- Ab 1.Try to describe the biological function of antibodies. 2. Terms: mAb / Ab / ADCC

31. 4. Terms: mAb / Ab / ADCC : Artificial / hybridoma / property / application mAb : Artificial / hybridoma / property / application Ab: Generation cell / structure/ classes/ functions ADCC: Ab / Fab-target / Fc-NK / cytotoxocity

32. How to understand the antibodies and complement are the molecules that are involved in both physiological and pathological consequences of immune response by using examples. Antibodies -- 4 分 : Physiological / Pathological Complement -- 4 分 : Physiological / Pathological

33. Complementarity determining region (CDR)

34. Functions of Antibody  Role of Ab alone  Role of Ab in complement activation  Role of Ab with effector cells

35. 1 、 Role of Ab alone  To Neutralize virus and toxins and blocks their biological activity (IgG).  To inhibit microbes attachment to mucosal epithelial cells (IgA).

38. 2 、 Role of Ab in complement activation To Activate the classical pathway of complement to lysis of the Ag by binding to Ag (IgG/ IgM).

41. 3 、 Role of Ab with effectors cells Macrophage and neutrophil: Opsonization and phagocytosis of microbes (IgG) NK cell and eosinophil: Antibody-dependent cellular cytotoxicity(ADCC) (IgG) Basophil and mast cell: Type I hypersensitivity – allergy (IgE)

43. FcrR (CD16) IgG NK cells

44. Sensitization against allergens pollen

45. Result – – Vasodilatation, – – Vascular Leakiness, – – Smooth Muscle Contraction, – – Mucus Secretion.

46. Overview of Immunology Organs and tissues Cells Molecules － Antibodies － Complement － Cytokines － MHC molecules Antigen (Ag) Immune Responses Control mechanisms Hypersensitivity Autoimmune disease Immunodeficiency Tumor immunology Transplantation Components of IS Functions of ISPathology of IR * IS: Immune system IR: Immune response

47. Components of IS -- Complement 1. Try to describe the pathways that are involved in activation of complement. 2. The functions of complement include …. 3. Term: MAC– activation of C / components / function

49. — — Anaphylatoxins: C3a, C5a — — Chemotaxis: C5a — — Opsonization: C3b — — Lysis of the microbes:MAC Functions of complement

50. Overview of Immunology Organs and tissues Cells Molecules － Antibodies － Complement － Cytokines － MHC molecules Antigen (Ag) Immune Responses Control mechanisms Hypersensitivity Autoimmune disease Immunodeficiency Tumor immunology Transplantation Components of IS Functions of ISPathology of IR * IS: Immune system IR: Immune response

51. Components of IS -- Cytokines 1. Try to explain how cytokines play their functions in immune response? 2. The are…… 2. The General characteristics of CKs are…… 3. Terms: CKs – generation / functions 3. Terms: CKs – generation / functions

52. Infected cells Virus Bacterium IL-1 Perforin Granzymes TNFa/TNFb Killing Cellular immunity BCR Antibody Neutralizing Complement activating NK ADCC Mq Phagocytosis MAC PMN Lysis C3b C3a/C5a Humoral immunity

53. General characteristics of CKs y Small molecules y Secreted by ： ⑴ Immune Cells; ⑵ Related cells - Autocrine - Paracrine - Endocrine y Bind with specific receptor y Effector : - Pleiotropy - Synergy - Redundancy - Antagonism

54. Overview of Immunology Organs and tissues Cells Molecules － Antibodies － Complement － Cytokines － MHC molecules Antigen (Ag) Immune Responses Control mechanisms Hypersensitivity Autoimmune disease Immunodeficiency Tumor immunology Transplantation Components of IS Functions of ISPathology of IR * IS: Immune system IR: Immune response

55. Components of IS – MHC molecules 1. Describe the biological functions of MHC molecules. 2. Terms: MHC -- genes / classes / functions HLA – Human MHC

56. Components of IS – MHC molecules MHC molecules are the important molecules in transplantation rejection, why ? Transplantation rejection = Immune response Ag : graft -- MHC-- 3 分 IR: APC -- MHC Direct pathway – 2.5 分 Indirect pathway – 2.5 分

57. Biological functions of MHC — — Immune Response — — Transplantation — — Related with diseases

58. Deletion T differentiation

60. Ag APCs Th1 Tc B Ab PMN NK Th2 Complement MHC in immune response Targetcells MHCCK MHCCK CKs CKs Target MHC

61. Ag presentation

62. Ag APCs Th1 Tc B Ab PMN NK Th2 Complement MHC in immune response Targetcells MHCCK MHCCK CKs CKs Target MHC

63. Virus infection

64. Recognition Activation Effects Rejection Immune response to graft

65. Overview of Immunology Organs and tissues Cells Molecules － Antibodies － Complement － Cytokines － MHC molecules Antigen (Ag) Immune Responses Control mechanisms Hypersensitivity Autoimmune disease Immunodeficiency Tumor immunology Transplantation Components of IS Functions of ISPathology of IR * IS: Immune system IR: Immune response

66. Functions of IS -- Ag 1. Try to explain the biological meanings of antigens that are related with medicine with 2 or 3 examples. 2. Terms: (1)Antigenic determinant (2) Hapten; (3) Adjuvant

67. (1)Antigenic determinant: Ag / specificity (2) Hapten: property / carrier (3) Adjuvant

68. Functions of IS – IR : innate immunity? 1. What kind of factors might be involved in innate immunity? 2. Terms: OOpsonization – Ab -Fc / C-CR / phagocytes/ target cells PRR– location / functions KIR – location / function KAR – location / function

69. Natural immune response Natural immune response ( Innate Immunity) — External defenses — Cell effects — Molecular effects

70. Mq/DCs Phagocytosis

71. NK KAR KIR

72. Functions of IS – IR : Adaptive immunity? 1. What kinds of factors determine the specificity of immune response? 2. How could lymphocytes be activated? 3. Describe the biological effects of humoral and cellular immune response. 4. Try to explain the relationship between the innate immunity and adaptive immunity.

73. Ag APC Th1 Tc B Ab PMN NK Th2 Complement Immune Response(IR) Targetcells MHCCK MHCCK CKs CKs

74. Adaptive Immune Response Adaptive Immune Response (Acquired Immunity) — Antigen presentation — Antigen recognition — Activation of cells — Effects

75. Antigen presentation — — Types of APCs ● Monocytes/Macrophage ● Dendritic cells ● B lymphocytes — — Pathways of antigen processing ● Class I processing pathway ● Class II processing pathway

77. Antigen Recognition   T cell recognition of Ag   B cell recognition of Ag

79. Adaptive Immune Response Adaptive Immune Response (Acquired Immunity) — Antigen presentation — Antigen recognition — Activation of cells — Effects

80. Activation of Cells — — Signals ● Antigen ● Co-stimulators ● Cytokines — — Signal transduction

82. Th-2

83. Adaptive Immune Response Adaptive Immune Response (Acquired Immunity) — Antigen presentation — Antigen recognition — Activation of cells — Effects

84. Effects of adaptive immune response Antibody response （ Humoral immunity ） T cell response （ Cellular immunity ）

85. Infected cells Virus Bacterium IL-1 Perforin Granzymes TNFa/TNFb Killing Cellular immunity BCR Antibody Neutralizing Complement activating NK ADCC Mq Phagocytosis MAC PMN Lysis C3b C3a/C5a Humoral immunity

86. Functions of IS – Control mechanisms How to understand the immune response to a particular Ag could be maintained in a proper level ?

87. Regulation of Immune Response Regulation of Immune Responses neuro- endocrine system + -

88. Overview of Immunology Organs and tissues Cells Molecules － Antibodies － Complement － Cytokines － MHC molecules Antigen (Ag) Immune Responses Control mechanisms Hypersensitivity Autoimmune disease Immunodeficiency Tumor immunology Transplantation Components of IS Functions of ISPathology of IR * IS: Immune system IR: Immune response

89. Pathology of IR – Hypersensitivity 1. Describe the mechanisms of hypersensitivity. 2. What kind of cells will be involved in type I hypersensitivity and how ? 3. Try to give some examples of diseases that are belong to type II and type III hypersensitivity.

90. Type-I Hypersensitivity (Allergy) Pollen Insect venoms Animal dander Fungi Worms Food Drugs Allergen

91. Result – – Vasodilatation, – – Vascular Leakiness, – – Smooth Muscle Contraction, – – Mucus Secretion.

92. Type-II Hypersensitivity (Ab-dependent Cytotoxic) Complement activation NK PMN Ag + Ab lysis Killing phagocytosis

93. Type-III Hypersensitivity (Immune Complex)

95. Type IV hypersensitivity (Delayed reaction)

96. Pathology of IR -- Autoimmune disease (AD) 1. Why does the immune system not attack self-tissue in normal conditions? 2. How could the self–tissue become the targets of immune system ? 3. How are the tissue destroyed by immune system ? 4. Terms: Self-tolerance : self-Ag / no response / specificity Self-tolerance : self-Ag / no response / specificity

97. Innate Immunity Adaptive Immunity -- Central tolerance -- Peripheral tolerance Self-tolerance

98. Self-tolerance – Innate Immunity -- Cells ： 1. Mononuclear phagocyte system 2. Granulocytes 3. Natural killer cells (NK) -- Molecule: Complement

99.   Central tolerance   Peripheral tolerance Self-tolerance -- Adaptive Immunity

100. Selection of T cells in thymus

101. DCs Th1 Tc B Ab PMN NK Th2 Complement Immune response to self – Self-Tolerance Targetcells MHCCK MHCCK CKs CKs Self

102. 3. How are the tissue destroyed by immune system ? Antibody mediated (type Ⅱ ) Immune complex mediated (type III) T-cell mediated (type IV)

103. Mechanisms Complement activation NK PMN Ag + Ab lysis Killing phagocytosis

104. Mechanism

105. Type IV hypersensitivity mediated AD Pancreatic Beta cells IDDM Loss of insulin production Brain cells Multiple sclerosis (MS) Demyelination of CNS, Paralysis

106. Pathology of IR -- Tumor 1. How could the tumor cells escape the surveillance of immune system? 2. What kinds of mechanisms could the tumor cells be destroyed by immune system? 3. Do you have any ideas about the strategies of immunotherapy? 4. Term: TAA—tumor/ quantity TSA – tumor/ quality

107. IL-1 Perforin Granzymes TNFa/TNFb Killing Cellular immunity !! BCR Antibody Complement activating NK ADCC Mq PhagocytosisLysis C3b Humoral immunity ! Tumor cells shed tumor-Ag shed tumor-Ag

108. Mechanisms of tumor escape Variation of tumor antigens Co-stimulator decrease Co-stimulator decrease Down-regulation of MHC expression Down-regulation of MHC expression Immune suppression of tumor Immune suppression of tumor Masking of tumor cell antigen Masking of tumor cell antigen

109. 1. Variation of tumor antigens

110. 2. Co-stimulator decrease

111. 3. Down-regulation of MHC expression

112. 4. Immune-suppression of tumor Tumor cells

113. 5. Masking of tumor cell antigen

114. Immunotheropy of tumors Preventive specific, T cells

115. Pathology of IR -- Transplantation rejection 1. What is the reason of transplantation rejection? 2.Do you have any ideas about how to overcome the transplantation rejection? 3. Terms: GVHR/ HVGR/ MLR(MLC) 4. Terms: GVHR: Ag-recipient / IS -graft HVGR: Ag – graft / IS - recipient MLR(MLC): method / application

116. Recognition Activation Effects Rejection Immune response to graft

117. Indirect and direct pathways

118. Prevention of rejection   Family grafting   Tissue typing   Cross-matching   Immunosuppression

119. Family grafting ac ac Twins Homozygotes

120. Tissue typing

121. Cross-matching -1 (Tritium)

122. graft APC Th1 Tc B Ab PMN NK Th2 Complement Suppress T cell activationgraft MHCCK MHCCK CKs CKs

123. Pathology of IR -- Immunodificiency Terms: AIDS – HIV-gp120/ CD4-T / IS / clinical

124. Overview of Immunology Organs and tissues Cells Molecules － Antibodies － Complement － Cytokines － MHC molecules Antigen (Ag) Immune Responses Control mechanisms Hypersensitivity Autoimmune disease Immunodeficiency Tumor immunology Transplantation Components of IS Functions of ISPathology of IR * IS: Immune system IR: Immune response