1. Overview of Immunology Organs and tissues Cells Molecules 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. Cells of Immune System

3. Cells of the innate immune system Mononuclear phagocytes Granulocytes NK cells Cells of the adaptive immune system T lymphocytes B lymphocytes Cells of Immune System

4.  Cell surface molecules expressed on various cell types in the immune system as markers: Lineage marker (e.g. CD3 on T cells) Maturation marker (e.g. CD4 / CD8 on T cells) Activation marker (e.g. CD25 on T cells)  Numbers of CD: CD1 – CD247 Cluster Differentiation(CD) System

5.  One cell can express more than one different CDs: e.g. T cells: CD2, CD3, CD4 or CD8, CD28…… B cells: CD19, CD20, CD21, CD79……  Different cells can express same CD: e.g. CD69 could be expressed on activated leukocytes: T cells, B cells, NK cells, nuetrophils, basophils Cluster Differentiation(CD) Molecules

6.  Mononuclear phagocytes  Granulocytes  NK cells Cells of the innate immune system

7. — Functions — Markers (Receptors) Mononuclear Phagocytes

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

9. Maturation

10. Cells of Mononuclear Phagocytes System

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

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

13. Mq/DCs Phagocytosis PAMP: pathogen-associated molecule pattern PRR Recognition Receptors: PRR

14. Recognition and killing of phagocytes By pattern recognition receptors(PRR)  Mannose receptors: mannose  CD14 : LPS  Scavenger receptors : carbohydrates /lipids  Toll like receptors (TLRs): PAMP (lipid-protein 、 LPS 、 RNA 、 DNA)

16. See:9-1

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

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

20. — Pattern recognition receptors(PRR): Recognition — Fc receptor (FcR, CD16): Opsonisation — Complement receptor (CR): Opsonisation Phagocytosis

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

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

23. See:8-2 Antigen presenting cells (APC)

24. Antigen that is presented on the APC could be recognized by T cell Recognized by T cells Antigen Presentation See:8-2

25.  Mononuclear phagocytes  Granulocytes  NK cells Cells of the innate immune system

26. — Neutrophils — Basophils — Eosinophils Granulocytes

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

29. — Majority of white blood cells — Contain: lysozyme, antibiotic peptides —Main function: phagocytosis — Chemotaxis: C5a — Opsonization: Ab and C3b Neutrophils (Polymorphonuclear cells PMNs)

32. — Neutrophils — Basophils (Mast cells) — Eosinophils Granulocytes

33. — Localization: Basophils － circulation Mast cells － tissues — Granule contents: Mediators Histamine Leukotrienes — Functions: Attract: Leukocytes － acute inflammatory response Allergy Basophils and Mast cells

36. Mediators: allergy – Vasodilatation, – Vascular permeability increase, – Smooth muscle contraction, – Mucous secretion.

37. Respiratory tract allergic rhinitis

38. Respiratory tract The lungs asthma

39. The skin Urticaria (hives)

40. — Present in circulation: — Granule contents: Peroxides/toxin Histaminase et al — Functions: Parasites killing Anti-inflammatory and allergy regulation Eosinophils

41.  Mononuclear phagocyte  Granulocytes  NK (Natural killer cells) Cells of the innate immune system

42. -- Functions -- Markers Natural Killer cells (NK cells)

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

44. NK KAR KIR

46. NK Ab CD16

47. NK IL-2 LAK Lymphokine activated killer cell

48. 1. KAR : (Killer activating receptors): Induce killing of the infected cells. 2. KIR: (Killer inhibitory receptor): Prevent NK from killing the normal cells. 3. CD16: Mediate ADCC (see:Ab) 4. IL-2R: Bind to IL-2 and become lymphokine activated killer cells ( LAK) (see:CK) Markers and functions of NK cells

49. Cells of the innate immune system Mononuclear phagocytes Granulocytes NK (Natural killer cells) Cells of the adaptive immune system T lymphocyte B lymphocyte Cells of Immune System

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

51. — T lymphocyte — B lymphocyte Cells of the adaptive immune system

52.  Classes  Functions  Markers T Lymphocyte

53. TH: T help cells (CD4 + CD3 + ) ¹TH1 ¹TH2 TC: T cytotoxic cells, CTL (CD8 + CD3 + ) Classes of T cells

54. Ag DCs Th1 Tc B Ab PMN NK Th2 Complement Targetcells MHCCK MHCCK CKs CKs Functions of T cells ？

55. — Recognition — Activation — Function Functions of T cells

56. Recognition

57. Composed of  （  ） or  chains （ 5-10% ） Recognize Ag peptide /MHC complex specifically; Mediates T cell activation. TCR

58. TCR + CD3:

60. Composed of γ 、 δ 、 ε and ζ chains; Mediates T cell activation signal into cells; Specific marker of T cells. CD3

61. MHC I MHC II

62. — CD4 On T helper cells Ligand to MHC class Ⅱ molecules — CD8 On T cytoxic cells Ligand to MHC class Ⅰ molecules

63. TCR -- MHC+ peptide CD4 -- MHC class II

64. TCR -- MHC + peptide CD8 -- MHC class I

65. — Antigen recognition — Co-stimulations — Cytokines Activations of T cells

66. Ag DCs Th1 Tc B Ab PMN NK Th2 Complement Targetcells MHCCK MHCCK CKs CKs Functions of T cells ？

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

70. TC Cells (CTL)

71. Release of lytic granules containing perforin and granzymes which enter the target cells Mechanisms of cytotoxicity Death of target cells See: 8-1

72. — Functions — Markers B Lymphocyte

73. — Resognition — Activation — Functions Functions of B cell

74. Th2

75. BCR + CD79 BCR Recognition of B cells

76.  BCR ( B cell receptor): 1)Cell surface of Ig ( IgM and IgD) 2)Specific binding with antigen  CD79 Mediate B cell activation  CD19/CD20 1 ） Co-receptors for B cell activation 2 ） Specific marker of B cells Markers of B cells

77. Th2

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

79. Th2 Function of B cells

80. BCR and TCR

81. BCR MHC

82. Site of maturation: MHC requirement for recognition: Markers: Functions Characteristics of B and T cells

83. Innate immunityAdaptive immunity Components chemical barrier Phagocytes NK cells T and B cells Cytokines Complement Antibodies Characteristics Receptors: Limited diversity Broad specificity Recognize many related molecules Receptors: Very large diversity Very narrow specificity Recognize a particular epitopes Immediate responseSlow response No memoryMemory Occurs in all metazoansOccurs in vertebrates only

84. Mq/DCs Phagocytosis PAMP: pathogen-associated molecule pattern PRR Recognition Receptors: PRR

85. NK KAR KIR

87. Th2

88. Ag DCs Th1 Tc B Ab PMN NK Th2 Complement Targetcells MHCCK MHCCK CKs CKs Crosstalk between Innate and Adaptive Immunity

89. 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.

90. 4. Terms: CD : Markers / functions TCR : Location / structure / function BCR : Location / structure / function PRR : Location / functions KIR : Location / functions KAR : Location / functions Questions: