Lectures 1 & 2 The immune system Overview

1. Lectures 1 & 2 The immune system Overview

2. Grading: Exam I 25% Exam II 25% State Exam 35% Lecture highlight 5% Final oral report 10%

3. LCME 514 Lectures Core Textbook

4. Oral reports: A student each lecture will take turn to summarize the last lecture’s highlights for 5 minutes, and take questions from other students

5. Experts in Clinical Immunology On 4/19/05, each student should present for 5 minutes as if he or she is an expert immunologist on the disease. This presentation accounts for 10% of the final grade. The students should include following components in their presentation: 1. What is the immunological mechanism of the disease? Describe the major immune components (cells, cytokines or molecules) and their functions in each disease. 2. What are the diagnosis criteria? 3. What are the therapy options?

6. Before lecture Read the textbook and try to understand all the terminologies in bold. These are building blocks so that we can build a “nice house of Immunology” in the class.

7. Lecture objectives What components make up the immune system? Cells, organs, cytokines and molecules involved in the immune system What is the goal of the immune system? To clear pathogens and cancer cells in our body Innate and adaptive immune responses Humoral Immunuty and Cell-Mediated Immunity What are the side effects of the immune system? Autoimmune diseases, Allergies, Transplantation Rejection

8. Figure 1-2 goal of the immune system The goal of the immune system Plus tumor cells

9. Figure 1-3 part 1 of 4

10. Figure 1-3 part 2 of 4

11. Figure 1-3 part 3 of 4

12. Figure 1-3 part 4 of 4

13. Figure 1-4 The territory to defend by the immune system: the physical barriers The immune system =The defense system of the body

14. Figure 1-7 Innate (immediate) and adaptive (late but antigen-specific) immune responses

16. Innate and adaptive responses work together Adaptive • Antigen-dependent • Slower (days) • T cells • B cells Innate • Antigen independent • Immediate (hours) • Neutrophils • NK cells • Macrophages • Dendritic cells *Innate immune responses help form adaptive immune responses, and Adaptive immune responses utilize the machinery of innate immunity for effector function

17. Cells of Innate Immunity Neutrophils NK cells Macrophages Mast cells Eosinophils Basophils

18. Cells of Adaptive Immunity Dendritic cells B cells T cells (CD4 or CD8)

19. Figure 1-5 Immune cell recognition of pathogens followed by destruction

20. Figure 1-6 Infection induces inflammation to recruit more immune cells

21. Hematopoiesis generates immune cells Stem cells: 1. Self renewal 2. Totipotency They are in bone marrow after fetal development. They make all myeloid and Lymphoid blood/immune cells T cell progenitors migrate to thymus and generate T cells B cell progenitors reside in bone marrow to make naïve B cells Immune cells = Soldiers

22. Figure 1-10 Hematopoiesis occurs in the adult bone marrow

23. Myeloid vs. Lymphoid cells Stem cells Myeloid cells Lymphoid cells T cells: T cell antigen receptor B cells: B cell antigen receptor NK cells: no antigen-specific receptor

24. Monocytes: Macrophage precursors • Origin : bone marrow • Antigen receptors: No • Function: to become macrophages • Present in blood circulation

25. Neutrophils: Phagocytes • Origin and maturation: Bone marrow • Antigen receptors: No • Function: Phagocytosis and killing of microorganisms • Where: in blood circulation • Sites of function: infection sites • Short life span

26. NK cells: natural killers • Origin : many (bone marrow and thymus) • Antigen receptors: No • Function: Kill tumor and virus-infected cells • Effector machinery (=weapons): perforins and granzymes

27. Macrophages: Phagocytosis and antigen presentation • Origin : bone marrow • Antigen receptors: No • Function: phagocytosis of microorganisms and antigen presentation to T cells • Present in various tissues in various forms (Kupffer cells, intraglomerular, alveolar, serosal, microglia, spleen sinus and lymph node sinus macrophages)

28. Dendritic cells (DC): transport antigens and activate T cells • Origin : bone marrow • Antigen receptors: No • Function: antigen presentation to T cells • Mechanisms: phagocytosis, cytokines (IL-4, IL-10, IL-12) and antigen-presentation through MHC molecules • Migration: From tissue infection sites to 2o lymphoid tissues

29. Mast cells: parasite killers • Origin : bone marrow • Antigen receptors: No • Function: to kill parasites • Sensor: IgE receptor • Effector machinery:cytotoxic granules, lipid mediators, cytokines and chemokines • Present in connective tissues

30. Eosinophils: worm (parasites) killers • Origin : bone marrow • Antigen receptors: No • Function: killing of antibody-coated parasites through release of killing mix (granule contents) • Effector machinery:cytotoxic granules, lipid mediators, cytokines and chemokines

31. Basophils: relatives of mast cells and eosinophils • Origin : bone marrow • Antigen receptors: No • Function: important effector cells in allergic disorders and immune responses to parasites • Sensor: IgE receptor • Effector machinery:cytotoxic granules, lipid mediators, cytokines and chemokines

32. T lymphocytes: master regulators of the immune system • Origin: Bone marrow • Maturation: Thymus • Differentiation to effector cells: secondary lymphoid tissues (Lymph nodes, spleen, Peyer’s patch, and tonsils) • Antigen receptors: Yes • Function: regulates humoral and cell-mediated immune responses • Mechanisms: cytokines, cell surface molecules, granules (cytotoxic T cells)

33. B lymphocytes: antibody producers • Origin and maturation: Bone marrow • Differentiation to plasma B cells: secondary lymphoid tissues (Lymph nodes, spleen, Peyer’s patch, and tonsils) • Antigen receptors: B cell receptor (cell surface immunoglobulins) • Function: Production of antibodies (IgM, IgE, IgA, and IgG) • Regulated by T cells

34. B lymphocytes Antigens+ T cell help

35. Figure 1-12 Circulating blood cells

36. Figure 1-13 Neutrophils: disposable phagocytes to clear pathogens

37. Figure 1-14 Macrophages engulf bacteria and produce inflammatory cytokines

38. Figure 1-15 The lymphatic system

39. Figure 1-16 Naïve lymphocytes encounter pathogens’ antigens in lymph nodes Activates lymphocytes Beginning of adaptive response

40. Figure 1-17 Antigens+DCs T cells B cells undergo differentiation to PC

41. Figure 1-18

42. Figure 1-19 Spleen does not have Afferent Lymphatics Spleen filters blood to search for antigens

43. Figure 1-20

44. Figure 1-21 Antigen receptors of B cells and T cells

45. Figure 1-22 Antibodies neutralize pathogens in an antigen-specific manner

46. Figure 1-23 Gene rearrangement to form antigen receptors on lymphocytes (immunoglobulins and T cell receptors)

47. Figure 1-24 Antibodies (B cells) bind whole proteins while TCR (T cells) binds small peptides

48. Figure 1-25 Peptides are presented to TCR by MHC class I or II molecules on APC (antigen presenting cells: B cells, dendritic cells and macrophages)

49. Figure 1-26 Viral antigen presentation to CD8+ T cells via MHC class I molecules

50. Figure 1-27 Bacterial antigen presentation to Th1 or Th2 CD4+ cells