1. Immunology Introductory course 2010 Series of lectures outlining - components of immune system, relevance to human disease

2. Immunology - an introduction Conleth Feighery MD John Jackson PhD Derek Doherty PhD Jacinta Kelly PhD* Department of Immunology, Trinity College and St. James’s Hospital * Our Lady’s Hospital for Sick Children, Crumlin

3. Immunology - purpose of course ? Learn some basic biology Learn about medical practice Learn to learn !

4. Immunology What is it all about ? How the ‘immune system’ works What does the immune system do ? 2 major functions - protects against infection causes ‘inflammation’

5. Major causes of ill-health Infection - 13 million die each year Inflammatory diseases - asthma Blood vessel disease - ‘atherosclerosis’ - heart attacks, strokes Cancer Immune system plays a significant role in all these disorders.

6. Medical case history. 1 24 year old male Coughing and wheezing at night Examination - nasal speech, breathless; wheezing DIAGNOSIS ?

7. Medical case history. 1 DIAGNOSIS - asthma Mechanism - “inflammation” in lungs, sinuses Cause - IgE, mast cells, white cells

8. Medical case history. 2 3 year old boy Serious lung infections x 5 Chest X-ray - “pneumonia” Small size, weight DIAGNOSIS ?

9. Medical case history. 2 DIAGNOSIS - immune deficiency Mechanism - unable to produce antibodies Antibodies “fight” infection

10. Medical case history. 3 7 year old girl Widespread red rash, high temperature Headache DIAGNOSIS - measles Cousin in same class, school - remains well EXPLANATION ?

11. Medical case history. 3 EXPLANATION - Cousin was given measles vaccine! How do vaccines work? Antibodies to vaccine develop - e.g. to measles vaccine “Educate” the immune system Real infection is rapidly eliminated

12. Immunology An approach to study - lectures discussion !! textbooks

13. Immunology - terminology Difficult ! “immunobabble” Learn some of the “language” - key terms Abbreviations - useful, standard Keep a list ? Use it !

14. Immunology - reading Self-learning is an objective of the University experience! Develop habit of seeking information - not relying on ‘being taught’ Internet offers endless opportunities for information

15. Textbooks A large variety exists - many too complex Few include full spectrum of this course B. Alberts - Molecular Biology of the Cell C.Janeway - Immunobiology H.Chapel, M.Haeney - Clinical Immunology

16. Immune system - components Essential ‘nuts, bolts’ white cells proteins organs circulatory system comprise - integral part biology

17. Immune system - components white cells - found in the blood, and tissues proteins - also found in blood, and tissues organs - such as the spleen, tonsils circulatory system – blood, lymphatics

18. Circulatory systems arterial - blood venous - blood lymphatic - lymph

19. Blood circulation Cells of blood include: red cells - 5000 x 10 3 per ml - carry oxygen platelets - 300 x10 3 per ml - help clotting white cells - 8 x 10 3 per ml - immune system

20. Bone marrow Source of cells

21. Major cells of the immune system T cell B cell lymphocytes neutrophilmonocyte

22. Multiple blood cell types

23. Fate of circulating blood cells Red cells - live 120 days; in blood vessels Platelets - live 10 days; in blood vessels Neutrophils - live ~ 1 day, migrate into tissues Lymphocytes - majority short lived - some live for years - constantly circulate

24. 2 types of lymphocytes T B Mature in thymus - regulate, kill Mature in the bursa - antibody

25. Lymphocytes Resting lymphocyte

26. Neutrophils ingest foreign material digest it “phagocytosis”

27. Neutrophils

28. Monocytes Macrophage in tissue “present” antigen monocyte

29. Monocyte

30. Antigen Definition Any substance which - causes a lymphocyte reaction reaction is specific to that lymphocyte clone - single type of lymphocyte which reacts to an individual antigen

31. Antigen Example - In the case of a B lymphocyte - Antibody is produced

32. Antigen Examples - infectious agent - bacteria, virus tissue - from another person - transplant food !!

33. Antigen - immune response Irradiation destroys bone marrow and cells of immune system Alberts et al.

34. Lymphocytes Importance discovered in 1950s 2 x 10 12 in body = size of liver able to transfer “immune responses” to irradiated animals

35. Lymphocytes - immune response Alberts et al.

36. T lymphocytes Originate in bone marrow Mature in thymus Enter circulation FUNCTION Control the immune system Eliminate infection - e.g. virus, fungus

37. Thymus - human

38. Importance of thymus Removal at birth - no T cells Absence in children - no T cells

39. Thymus in birds Alberts et al.

40. Thymus absence in child Smallpox vaccination - spread throughout body [live virus]

41. B lymphocytes Originate in bone marrow Mature in bursa (equivalent) Enter circulation FUNCTION Become antibody producing “plasma” cells Absence - no antibody

42. B cells develop in bursa Bursa in man unknown - may be the bone marrow Alberts et al.

43. B cell identification B cells have a specific receptor for antigen antibody molecule

44. B cell binding antigen B cells have a specific receptor for antigen antigen

45. Antibody molecule

46. T and B cells - electron microscope Alberts et al. Resting lymphocyteActivated B cell Activated T cell

47. T cells - antigen receptor alpha chain beta chain

48. Monocytes Macrophage in tissue “present” antigen monocyte

49. Macrophage - appearances Monocyte Macrophage - scanning electron microscope

50. Monocytes Originate in bone marrow Enter circulation Migrate into tissues - change shape ---- “macrophage” Phagocytic cell Present antigen to T cells

51. Dendritic cells Antigen presenting cells - key role in initiating T cell response to antigen

52. Macrophage/dendritic cell - collaboration T cell - help - suppress - kill B cell antibody

53. Immune system Non-specific Neutrophils Macrophages Complement Mechanical “INNATE” Specific Lymphocytes “ADAPTIVE”

54. Immune system InnateAdaptive work together close collaboration

55. Specific immunity T and B lymphocytes Specific response to a single antigen Memory for that response