Immune system. Self/non-self recognition. Memory. The state of protection from infectious disease. Acceptance vs rejection

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2 Immune system The state of protection from infectious disease Self/non-self recognition 自我 非我 Acceptance vs rejection Memory 疫苗 2

3 Microbes Commensal Microbes 共生菌 Normal flora: usually confined to certain areas of the body, including the skin, mouth, large intestine, and vagina

4 Pathogens Primary pathogens causing overt disease in most healthy people Establishment of infection

5 Establishment of infection Colonize the host Antigen (Ag) Find a nutritionally compatible niche in the host s body Replicate, using host resources Avoid, subvert, or circumvent the host s innate and adaptive immune responses Exit and spread to a new host

6 Design of immune system

7 The growth of pathogen: Survival of host (not killing the host too quickly) Adaptive immunity Innate immunity

8 Immunity Innate immunity Adaptive immunity Humoral immunity B cells: Antibody Cell-mediated immunity (CMI) T cells

9 Immune recognition Innate (non-specific) immunity Adaptive (specific) immunity

10 Innate immunity Physical barrier Biochemical barrier Phagocytes Inflammation Immune cells

11 Physical & biochemical barrier 皮脂 Defensin Small intestine

12 Biochemical barrier The complement system A large and complex group of proteins Proenzymes / Zymogens Inactive form in plasma Activation of complement Proteolytic cleavage Removal of an inhibitory fragment Exposure of the active site 12

13 Biochemical barrier Complement producers Liver hepatocytes Blood monocytes Tissue macrophages GI epithelial cells 13

14 Biochemical barrier Complement

15 Complement Pore formation and lysis

16 abg C4b C1s a

17 Innate immunity Physical barrier Biochemical barrier Phagocytes Inflammation Immune cells

18 Complement Inflammation Phagocytes Induction of adaptive immunity

19 Innate immunity Phagocytes: phagocytosis 吞噬細胞 吞噬作用 調理作用 granules

20 Innate immunity ( 發炎反應 ) Inflammation (cells, soluble mediators)

21 Design of immune system

22 Part I Cells Organs & tissues Functions Part II Antibody response Part III T cell response

23 Part I Cells Organs & tissues Functions

24 Immune cells Innate immunity Adaptive immunity WBC Myeloid cells Lymphoid cells Macrophages/ Dendritic cells (DC) Granulocytes B T CD4 CD8 (Th) (Tc) NK (Natural killer cells)

25 Immunity Innate immunity Adaptive immunity Humoral immunity Cell-mediated immunity (CMI)

26 Extracellular Ag Altered self Intracellular Ag Colony

27 Function of immune cells Ag elimination is based on Ag location Humoral response Ag Innate Adaptive Extracellular Phagocytes 2 B cells CD4 Th Intracellular NK 1 CD8 Tc cells (Altered self) Cytotoxicity Cell-mediated immunity (CMI)

28 Phagocytes Extracellular NK Intracellular Adaptive immunity CMI Humoral immunity

29 Extracellular Ag Innate immunity Phagocytes: chemotaxis & phagocytosis RBC Ag recognition

30 Innate immunity Pattern recognition

31 Phagocytes Innate immunity Recognition of Conserved Features of Pathogens

32 Intracellular Ag Innate immunity Infected cells Altered self

33 Adaptive immunity Lymphocytes Ag-specific receptor

34 Lymphoid organs and tissues Primary (Central) Bone marrow Thymus Secondary (Peripheral) Lymph nodes Spleen Peyer s patches

35 Immune design Adaptive immunity

36 Lymph node distribution in the body

37 Lymph node DC HEV T

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39 Inflammation Route Antigen-presenting cells (APC)

40 DC T

41 Adaptive immunity 1. Antigen specificity 2. Diversity 3. Immunological memory 4. Self tolerance

42 Design of immune system Pattern recognition Ag-specific recognition

43 Adaptive immunity B cell development and humoral immunity Primary (Central) Immune diversity Low frequency Specificity Secondary (Peripheral) Clonal selection

44 B

45 Adaptive immunity Clonal expansion & differentiation

46 Adaptive immunity Memory response

47 Part II Antibody response

48 Antibody structure

49 Fab Fc Antibody structure Effector function

50 Antibody structure Epitope

51 Antigen-antibody interaction Immune complex

52 Effector function Five classes of antibody

53 Ab is a mediator to activate downstream immune pathways

54 IgM

55 Memory response IgG IgM C

56 Effector function Five classes of antibody

57 Opsonization: Enhanced phagocytosis by mediators (opsonin) IgG

58 Effector function Five classes of antibody

59 IgE

60 IgA transport

61 Function of antibody Binding FcR Complement activation Neutralizing (Blocking)

62 Part III T cell response CD4 Th Ag specific recognition (Signal 1) Costimulation (Signal 2) Cytokine (Signal 3) B cells CD8 Tc cells

63 Ag specific recognition (Signal 1) T cell Receptor (TCR)

64 T cell recognition & activation Antigen-presenting cells (APC)

65 T-DC interaction APC

66 T cell recognition: MHC restriction

67 MHC HLA: Human leukocyte antigen

68 MHC 內 APC

69 Ag processing & presentation to CD4 T 外

70 Ag processing & presentation to CD8 T 內

71 Co-receptor: CD4 & CD8

72 T cell activation & expansion Costimulation (Signal 2)

73 Th cell differentiation

74 Cytokine (Signal 3) in T cell differentiation Cytokine: Effector function 1 Costimulation 內

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77 Costimulation APC 2

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79 Innate immunity Adaptive Immunity (Humoral, CMI)

80 Infectious diseases Public health measures Medical intervention: Anti-microbial drugs, Vaccination, etc.

81 Persistent infection Host-pathogen relationship Immune evasion Persistence

82 Type of interaction between microbes and immune responses in microbial pathogenesis Disease Immunopathology Pathogens colonize asymptomatically in hosts with normal immune responses