1. Lectures 1 & 2 The immune system Overview

2. Grading:
Exam I %
Exam II %
State Exam %
Lecture highlight %
Final oral report %

3. Textbook
LCME 514 Lectures
Core

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. goal of the immune system
The goal of the immune system
Figure 1-2
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. The territory to defend by the immune system: the physical barriers
Figure 1-4
The immune system =The defense system of the body

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

16. Innate and adaptive responses work together
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. Immune cell recognition of pathogens followed by destruction
Figure 1-5

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

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

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. Circulating blood cells
Figure 1-12

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

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

38. The lymphatic system
Figure 1-15

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

40. Antigens+DCs
T cells
Figure 1-17
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. Antigen receptors of B cells and T cells
Figure 1-21

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

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

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

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

51. Selection and expansion of antigen specific T and B cells
Figure 1-8

52. Figure 1-28 Generation and selection of T cells
The thymic selection processes are to generate T cells with functional TCRs that are not autoreactive.

53. Antibodies neutralize and opsonize
Figure 1-29 part 1 of 2

54. Figure 1-29 part 2 of 2

55. Typical time course of adaptive immune responses
Primary response
Slow (2 weeks)
Weak
Secondary
Fast (several days)
Vigorous

56. The impact of vaccination

57. Unwanted immune response: allergies

58. Unwanted immune response: autoimmune diseases

59. The goal of a balanced immune system
[Pathogens]= 0
[tumor cells]= 0
Immunity

60. Allergy and hypersensitivities
Immune response to allergens
[Pathogens]= 0
[tumor cells]= 0

61. [tumor cells] >> 0
Cancer
[tumor cells] >> 0
Immune response to tumor cells

62. Autoimmune diseases
Immune response to self antigens
[Pathogens]= 0
[tumor cells]= 0

63. [tumor cells] >> 0
Immunodeficiency
[Pathogens] >> 0
[tumor cells] >> 0
Immunity to pathogens and cancer cells
e.g. AIDS patients

64. Immune responses can be both beneficial and harmful
Figure 1-34