Dr. Fang-Ping Huang Department of Pathology,

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Dr. Fang-Ping Huang Department of Pathology,

  1. 1. Dr. Fang-Ping Huang Department of Pathology, Immunology Division, Room 216 Tel. 2855 4864 Email: fphuang@hkucc.hku.hk
  2. 2. <ul><li>The immune system - an overview (basic concepts, features) </li></ul><ul><li>Developmental biology of the immune system (Dr. L. Lu) </li></ul><ul><li>Recent advances in lymphocyte lineage commitment (Dr. L. Lu) </li></ul><ul><li>Apoptosis & the molecular cell death pathways (Dr. L. Lu) </li></ul><ul><li>Antigen recognition by T cells & its MHC restrictions </li></ul><ul><li>Pathways of antigen processing, presentation & co-stimulations </li></ul><ul><li>Dendritic cells & the initiation of immune responses </li></ul><ul><li>Immune regulation & dys-regulation in health & in diseases </li></ul>Essence and Advances in Contemporary Immunobiology
  3. 3. <ul><li>Basic concepts in immunology </li></ul><ul><li>Vaccination & the history of immunology </li></ul><ul><li>Types of immunity </li></ul><ul><li>The adaptive immune system </li></ul><ul><ul><li>Immunological specificity & memory </li></ul></ul><ul><ul><li>B cells & humoral immune response </li></ul></ul><ul><ul><li>T cells & cell-mediated immune response </li></ul></ul><ul><li>The concepts of ‘self/non-self’ & ‘self-tolerance’ </li></ul>The immune system – an overview
  4. 4. Basic concepts in Immunology <ul><li>Organisms and microorganisms </li></ul><ul><ul><li>Bacteria, viruses, fungi & parasites </li></ul></ul><ul><li>Infections and diseases </li></ul><ul><li>Infection == disease </li></ul><ul><li>Mechanisms of defense </li></ul><ul><li>The immune system </li></ul><ul><ul><li>Cells & soluble factors </li></ul></ul><ul><li>Immunity and Immunology </li></ul>
  5. 5. ‘ Immunity’ <ul><li>Original meaning: </li></ul><ul><ul><li>“ exemption from taxes” </li></ul></ul><ul><li>Other extended meaning: </li></ul><ul><ul><li>“ diplomatic immunity” </li></ul></ul><ul><li>In the context of Immunology: </li></ul><ul><ul><li>collective mechanisms against diseases </li></ul></ul>
  6. 6. Edward Jenner (1749-1823) & The Discovery of Vaccination (1796) “ Vaccinia (cowpox)” & “ human smallpox”
  7. 7. Eradication of smallpox (1979, WHO)
  8. 8. Vaccination <ul><li>A process of induction of immunity to a pathogen by </li></ul><ul><li>deliberate injection of a weaken, modified or related form of </li></ul><ul><li>the pathogen which is no longer pathogenic. </li></ul>
  9. 9. Other historic events & important findings: <ul><li>L. Pasteur (1880s) </li></ul><ul><ul><li>Vaccines against cholera, and rabies </li></ul></ul><ul><li>R. Kock (late 19 th century) </li></ul><ul><ul><li>Infections caused by microorganisms </li></ul></ul><ul><li>P. Ehrlich et al. (1890s) </li></ul><ul><ul><li>Serum factors transfer of immunity </li></ul></ul><ul><li>Behring & Kitasato (1890s) </li></ul><ul><ul><li>Antibodies in serum bound to pathogens </li></ul></ul><ul><li>Porter & Edelman (1960s) </li></ul><ul><ul><li>Antibody structure </li></ul></ul><ul><li>J. Gowans (1960s) </li></ul><ul><ul><li>Immunological importance of lymphocytes </li></ul></ul>
  10. 11. Size of the immune system?
  11. 12. Dendritic cell (sentinel)
  12. 14. Lymph Node
  13. 16. The bursa of Fabricius in birds
  14. 17. Cells, tissues and organs of the immune system <ul><li>Immune cells are bone marrow-derived, & distributed through out the body </li></ul><ul><li>Primary lymphoid organs: </li></ul><ul><ul><li>Thymus: T cell maturation </li></ul></ul><ul><ul><li>Bone marrow (bursa of Fabricius in birds): B cell maturation </li></ul></ul><ul><li>Secondary lymphoid organs: </li></ul><ul><ul><li>Lymph nodes </li></ul></ul><ul><ul><li>Spleen </li></ul></ul><ul><ul><li>Mucosal lymphoid tissues (lung, gut) </li></ul></ul>
  15. 18. Questions: <ul><li>How may vaccines protect us from infections? </li></ul><ul><li>What may actually occur in our immune system following a vaccination? </li></ul>
  16. 19. Types of immunity <ul><li>Innate (natural) immunity </li></ul><ul><ul><li>Phagocytes etc. </li></ul></ul><ul><ul><li>Early, rapid responses, but limited & ‘non-specifc’ </li></ul></ul><ul><li>Adaptive (acquired) immunity </li></ul><ul><ul><li>Lymphocytes (B & T cells) </li></ul></ul><ul><ul><li>Take time but powerful - ‘ specificity + memory ’ </li></ul></ul>
  17. 20. Measles attacks & immunological memory
  18. 21. “ Memory” in adaptive immunity <ul><li>1 st infection  memory  2 nd infection </li></ul><ul><li>slow response fast response </li></ul><ul><li>pathogen proliferate pathogen killed </li></ul><ul><li>disease no disease </li></ul><ul><li>symptoms no symptom </li></ul>
  19. 22. Memory & specificity – key features of the adaptive immunity
  20. 24. Immunological memory & vaccination <ul><li>Natural infections: </li></ul><ul><li>1 st infection  memory  2 nd infection </li></ul><ul><li>slow response fast response </li></ul><ul><li>pathogens multiply pathogens disposed </li></ul><ul><li>Symptoms/disease no disease </li></ul><ul><li>Vaccination  memory  nature infections </li></ul><ul><li>no disease fast response </li></ul><ul><ul><li>pathogens disposed </li></ul></ul><ul><ul><li>no disease </li></ul></ul>
  21. 25. Vaccination protects us from infection by inducing the adaptive immune response, but bypassing the need for a primary infection
  22. 26. Theoretical basis for immunological specificity and memory <ul><li>Theory of Clonal Selection </li></ul><ul><li>Establishment of lymphocyte memory pool </li></ul>
  23. 27. 1 2 4 3 Ehrlich’s “Side-chain Hypothesis” (1900)
  24. 28. Burnet’s “Clonal Selection” Theory Each lymphocyte produces one type of Ag receptors only, antigen selects and stimulates cells carrying receptors specific for the antigen 1 n 2 2 2 2 2 2 2
  25. 29. s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s
  26. 30. Immunological memory <ul><li>The ability of the immune system to respond more rapidly and effectively to specific pathogens that have been encountered previously. </li></ul><ul><li>Reflection of the pre-existence of a clonally expanded population (pool) of antigen specific lymphocytes. </li></ul>
  27. 31. <ul><li>Humoral immune responses </li></ul><ul><ul><li>B cells and antibodies </li></ul></ul><ul><li>Cell mediated immune responses </li></ul><ul><ul><li>Cytotoxic T cell (Tc) </li></ul></ul><ul><ul><li>Helper T cells (T H ) </li></ul></ul>The adaptive immune mechanisms
  28. 32. <ul><li>The Immune Recognition Molecules of the Adaptive Immune System </li></ul><ul><li>Immunoglobulin (Ig) </li></ul><ul><ul><li>B Cell Receptor (BCR) </li></ul></ul><ul><ul><li>Antibody (Ab) </li></ul></ul><ul><li>T Cell Receptor (TCR) </li></ul><ul><li>Major Histocompatibility Complex (MHC) </li></ul>
  29. 33.                                 B Cells work chiefly by secreting soluble substances known as antibodies (Ab)
  30. 34. Ab basic structure domains
  31. 35. Ab V and C regions
  32. 36. <ul><li>Neutralization: e.g. toxins, viruses </li></ul><ul><li>Opsonization: bind pathogens for recognition by other immune cells (e.g. phagocytes) </li></ul>Antibody functions
  33. 39. Tc Target Tc
  34. 41. T H cells play a central role in the immune system
  35. 42. CD4 + T cells in HIV infection
  36. 43. Immunological tolerance <ul><li>A state of unresponsiveness to a particular Ag - Ag specific </li></ul><ul><ul><li>to Ags derived from body’s own tissues/cells - self tolerance </li></ul></ul><ul><ul><li>to pathogen-derived/foreign Ags </li></ul></ul>
  37. 44. The concepts of immunological ‘ self ’ & ‘ non-self ’ <ul><li>Immune system does not attack self tissues or cells under normal condition, but how? </li></ul><ul><ul><li>Central tolerance – “thymic education” </li></ul></ul><ul><ul><li>Peripheral tolerance – failed-safe mechanisms </li></ul></ul>
  38. 45. <ul><li>Early in life (foetal stage) </li></ul><ul><li>T cells are important, which develop in the thymus </li></ul><ul><li>TCR specificities: randomly generated  many auto-reactive </li></ul><ul><li>T cells recognize self components (Ag) in the thymus  removed </li></ul><ul><li>Non-self reactive cells  selected, matured & exported </li></ul>Central tolerance – “ thymic education”
  39. 46. <ul><li>Post-thymic “continuing education” </li></ul><ul><ul><li>not all self Ags present in the thymus </li></ul></ul><ul><ul><li>some auto-reactive cells can escape </li></ul></ul><ul><li>Mechanisms: </li></ul><ul><ul><li>Deletion </li></ul></ul><ul><ul><li>Inactivation (anergy) </li></ul></ul><ul><ul><li>Suppression </li></ul></ul>Peripheral tolerance
  40. 47. Does the immune system mount responses simply to anything that is “non-self”? A question for thoughts:
  41. 48. <ul><li>Immunity: </li></ul><ul><li>Innate (natural) </li></ul><ul><li>Adaptive (acquired) </li></ul><ul><li>Humoral (B cells, Abs) </li></ul><ul><li>Cellular (T, NK, MQ) </li></ul><ul><li>The adaptive immunity: </li></ul><ul><li>Key features: specificity & memory </li></ul><ul><li>Types: humoral & cell-mediated responses </li></ul><ul><li>Key players: T & B lymphocytes </li></ul><ul><li>T H cells play a central role in the induction & maintenance of immune responses </li></ul><ul><li>Principle of vaccination: </li></ul><ul><li>Vaccination protects us from infection by inducing protective immunity, through establishment of specific immunological memory but bypassing the need for primary infection </li></ul><ul><li>Immunological tolerance: </li></ul><ul><li>Tolerance induction is Ag specific </li></ul><ul><li>Central & peripheral mechanisms </li></ul>Summary

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