1. Immunology ; “Science of Self/Non-self Discrimination”

2. Immunity ; The state of protection from infectious disease. –“ immunis” ; exempt, –individuals who had recovered from certain infectious diseases were thereafter protected from the disease. Immune response –Recognition ; specificity –Response ; effector response : eliminate or neutralize the organism memory response : rapid & heightened immune reaction Innate immunity vs. adaptive immunity

3. Smallpox; a historical perspective The most destructive disease in history In the 20th century, more than 300 million people succumbed to Smallpox. Variolation Ancient Chinese and Indian physicians (11th century) recognize the practice to inject pus from smallpox lesions into healthy individuals in hope of inducing mild disease. Introduced into England in 1721 Many people contracted smallpox from variolation (1-2% fatality), but, much better alternative than natural smallpox (25% of whole population and 40% in young children).

4. The first Vaccine Edward Jenner (1749-1823) ; Milkmaids who had been exposed to cowpox (a mild disease in humans) were protected against smallpox (1796) Louis Pasteur; - Vaccination (vacca = cow in Latin) in 1881 - Attenuated rabies viral vaccine (1885); Safer and more efficient methods for the preparation of larger quantity of vaccine. Yellow fever virus vaccine (1935) Influenza virus vaccine(1936)

5. cartoon from 1802

6. Effect of Vaccination Measles Vaccine Smallpox Vaccine

7. 20th century flu pandemics PandemicYear Influenza A virus subtype People infected (approx) Deaths (est.) Case fatality rate 1918 flu pandemic 1918–19H1N1 0.5 to 1 billion (near 50%) 20 to 100 million>2.5% Asian flu1956–58H2N22 million<0.1% ? Hong Kong flu1968–69H3N21 million<0.1% 2009 flu Pandemic 2009-10new H1N11.6 million20,0001.2% Seasonal fluEvery year mainly A/H3N2, A/H1N1, and B 5–15% (340 million – 1 billion) 250,000– 500,000 per year <0.05% http://en.wikipedia.org/wiki/2009_flu_pandemic_by_country

8. Ch1. Elements of the Immune System and their Roles in Defense

9. The four kinds of pathogen that cause human disease

11. Human pathogens

13. Anatomic Barriers – Skin, Mucous membranes, Cilia, Normal flora Physiological Barriers – Temperature, Low pH, Chemical Mediators – Lysozyme, Interferon, Complement, Collectin, TLR Phagocytic/endocytic Barriers – Phagocytosis (tissue macrophages, neutrophils) – Endocytosis Inflammatory Barriers – redness, swelling, heat, pain Innate Immunity (Nonspecific Immunity)

14. Physical barriers

16. Innate immunity Recognition & Effect Mechanism Inflammation

17. Inflammatory response

18. Inflammation

19. Antigenic Specificity ; Ab, TCR – Antigenic determinant (epitope) – Antigen vs. Immunogen Diversity – Multiple germ-line gene segments ; random arrangement – Generation of Ab diversity exceeds 10 10 Immunologic Memory – Plasma cells ; clonal expansion – Acquired immunity – Vaccine Self/non-self Recognition Adaptive Immunity (Specific Immunity)

20. Antigenicity vs. Immunogenicity Antigen –A substance that reacts with the products of an immune response stimulated by a specific immunogen (Ab, TCR) –Sugars, lipids, hormones, complex carbohydrate, nucleic acids, proteins.. –Incomplete antigen (hapten, lipids) is unable to induce immune response Immunogen –A substance that is able to induce a humoral antibody and/or cell- mediated immune response rather than immunological tolerance. –>1 kDa, proteins or polysaccharides. –Depends on the genetic capacity of the host to respond to rather than merely upon the antigenic properties of an injected immunogen

21. Innate vs. adaptive immunity

22. Selection of lymphocytes by a pathogen

23. Maturation and clonal selection of B lymphocytes

24. Hematopoiesis

25. Hematopoietic stem cell (HSC) Multi-potent, self-renewal Erythrocytes, leukocytes, megakaryocytes Differentiation ; lineage commitment, loss of self-renewal Lymphoid progenitor Myeloid progenitor The site of hematopoiesis during development

26. Abundance of leukocytes in human peripheral blood

27. Surface marker of cell membrane ; CD (cluster of differentiation) http://mpr.nci.nih.gov/prow http://mpr.nci.nih.gov/prow

28. Cells of the Immune System Lymphoid cells ; –central cells of immune response (99% of the cells in lymph) –Adaptive immunity –B cell, T cell, NK (Natural Killer) cell Mononuclear phagocytes ; –Monocytes in the blood –Machrophages in the tissue ; phagocytosis, opsonization –Antigen processing and presentation Granulocytic cells ; –Multilobed-nucleus, granulated cytoplasm –Neutrophil, eosinophil, basophil

29. Lymphocytes B cell From Bursa or Bone marrow Membrane-bound immunoglobulin (Antibody) ; B cell receptor 1.5 x 10 5 receptors/cell T cell From Thymus T cell receptor (TCR) MHC restriction Helper T cells ; secrete cytokine Cytotoxic T lymphocyte (CTL) ; eliminate altered self-cells NK cell

30. Effector cell Naïve cell Naïve vs. effector cells

31. Natural killer (NK) cells 5-10% of lymphocytes Host defense against tumor, virus-infected cells Non-specific cell mediated response Granulocytes Neutrophil ; - 50-70% of white blood cells - Indicator of infection ; leukocytosis - phagocytosis Eosinophil ; - phagocytosis - anti-parasitic Basophil ; - allergic response, non-phagocystic Mast cells ; - Allergy (histamine)

32. NK cells are involve in the early response to viral infection

34. Role of Neutrophil

35. Macrophage Monocytes in blood & Macrophages in the tissues Enlarge & increase lysosomes ; lysozyme, hydrolytic enzymes

36. Role of Macrophage

37. Dendritic cells (DC) ; APC Phagocytosis Migration into Lymph node Antigen presentation (MHC II)

38. Platelet & RBC

39. Hematopoiesis

40. Organs of the Immune system (function) Primary (generative) lymphoid organs ; –provide appropriate microenvironments for the development and maturation of lymphocytes –Thymus, Bone Marrow Secondary (peripheral) lymphoid organs ; –Mature lymphocytes interact with antigen –Spleen, Lymph node, –MALT ; GALT- Pyer’s patch, Appendix, Tonsil Tertiary lymphoid tissues ; cutaneous-associated lymphoid tissues Lymphatic system, blood vessels ; connect organs

41. Human lymphoid system

43. Lymph Node

45. Spleen

46. GALT

47. Immunologic Memory Differences in the Primary and Secondary Immune Response

48. Successful vaccination