Understanding immunology for internists 1


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Understanding immunology for internists 1

  1. 2. Understanding Immunology Dr. Ahmed Elshebiny , MD Lecturer of Internal Medicine Faculty of Medicine, Menoufyia University Former Clinical Research Fellow, Joslin Diabetes Center, Harvard University
  2. 3. Immunology Course <ul><li>Basics: </li></ul><ul><li>Immune system and disease </li></ul><ul><li>Diseases: </li></ul><ul><li>Immunopatholy </li></ul><ul><li>Applications: </li></ul><ul><li>Therapeutic applications </li></ul>
  3. 4. Immune system and disease <ul><li>Immunity </li></ul><ul><li>Immune system </li></ul><ul><li>Innate Immunity </li></ul><ul><li>Adaptive Immunity </li></ul><ul><li>Immune Recognition </li></ul><ul><li>Cells of the Immune system </li></ul><ul><li>Complement </li></ul><ul><li>Immunoglobulins </li></ul><ul><li>Cytokines </li></ul><ul><li>Human disease & Immunity </li></ul><ul><li>Immunopathology </li></ul><ul><li>Diagnostics </li></ul><ul><li>Therapeutic applications </li></ul>Structure and Function of The System Cells and Molecules of Immunity Introduction to Clinical Immunology
  4. 5. Immunity
  5. 6. Immunity is characterized by: <ul><li>Specificity – activated by and responds to a specific antigen </li></ul><ul><li>Versatility – is ready to confront any antigen at any time </li></ul><ul><li>Memory – “remembers” any antigen it has encountered </li></ul><ul><li>Tolerance – responds to foreign substances but ignores normal tissues </li></ul>
  6. 7. History of discovery of immunity <ul><li>“Immune” meaning </li></ul><ul><li>Noticing immunity centuries ago </li></ul><ul><li>Small pox </li></ul><ul><li>Edward Jenner </li></ul><ul><li>Recent developments </li></ul>
  7. 9. 1 st Line defense: Physical and chemical barriers <ul><li>Skin – acts as a barrier to invasion </li></ul><ul><li>Sweat – has chemicals which can kill different pathogens . </li></ul><ul><li>Tears - have lysozyme which has powerful digestive abilities that render antigens harmless . </li></ul><ul><li>Saliva – also has lysozyme . </li></ul><ul><li>Mucus - can trap pathogens, which are then sneezed, coughed, washed away, or destroyed by chemicals . </li></ul><ul><li>Stomach Acid – destroys pathogens </li></ul>
  8. 10. Innate Adaptive Immunity Cellular Humoral Cellular Humoral Let us see this video about immunity
  9. 11. Inflammation <ul><li>Inflammation is a nonspecific response of living tissue to localize and eliminate the injurious agent </li></ul>Immune Response
  10. 12. Inflammation <ul><li>The word inflammation means &quot;setting on fire&quot; (16th century), and the process has been known since ancient Egyptian times (c. 2500 B.C) </li></ul><ul><li>The cardinal signs of redness, swelling, heat, and pain were described by Celsus (first-century A.D.), and loss of function was added by Galen (130-200 A.D) </li></ul>
  11. 13. Acute phase changes <ul><li>characterized by pronounced behavioral, physiologic, biochemical and nutritional changes </li></ul><ul><li>Acute phase reactants </li></ul><ul><li>Acute phase proteins </li></ul>
  12. 14. C-reactive protein <ul><li>named for its capacity to precipitate the somatic C-polysaccharide of Streptococcus Pneumoniae. </li></ul><ul><li>Systemic marker of inflammation </li></ul><ul><li>produced by hepatocytes, predominantly under transcriptional control by the cytokine IL-6 </li></ul>
  13. 15. The Immune system <ul><li>The immune system recognizes, attacks, destroys, and remembers each pathogen that enters the body.   </li></ul><ul><li>It does this by making specialized cells and antibodies that render the pathogens harmless. </li></ul>
  14. 17. Questions ? <ul><li>What Happens during an infection ? </li></ul><ul><li>How can immune cells distinguish foreign invaders from our own cells ? </li></ul><ul><li>How can we make 100,000,000 different antibodies with only 30,000 genes ? </li></ul>
  15. 18. Cells of the immune system T-cell development
  16. 19. Cells of the immune system
  17. 20. Polymorphonuclear cells 1- Neutrophils <ul><li>Stored in bone marrow </li></ul><ul><li>Released in response to infection </li></ul><ul><li>Have surface receptors for IgG, IgA, complement </li></ul><ul><li>Phagocytose and destroy bacteria </li></ul><ul><li>Short lived </li></ul><ul><li>Dead neutrophils make a part of pus </li></ul>
  18. 21. Polymorphonuclear cells 2-Basophils and mast cells <ul><li>Basophil circulate </li></ul><ul><li>Mast cells are tissue bound </li></ul><ul><li>Released in response to infection </li></ul><ul><li>Have surface receptors for IgE, complement C3, C5 </li></ul><ul><li>Produce histamine, prostaglandins, leukotrienes and proteases </li></ul><ul><li>Involved in immune response to parasites </li></ul><ul><li>Involved in immediate hypersensitivity </li></ul>
  19. 22. Polymorphonuclear cells 3-Eosinophils <ul><li>Allergy </li></ul><ul><li>Have surface receptors for IgG, complement C3, C5 </li></ul><ul><li>Also binds to IgE but less than mast cells or basophils </li></ul><ul><li>Phagocytose antigen antibody complexes </li></ul>
  20. 23. Macrophage <ul><li>In the tissues </li></ul><ul><li>Long lived </li></ul><ul><li>Initiate immune responses as they display antigens from the pathogens to the lymphocytes. </li></ul>
  21. 24. Phagocytosis
  22. 25. Lymphocytes <ul><li>B and T cells mature then circulate in the blood and lymph </li></ul><ul><li>B-cells mature in bone marrow </li></ul><ul><li>T-cells mature in thymus </li></ul>
  23. 26. B-Lymphocytes <ul><li>The huge variety is caused by genes coding for abs changing slightly during development. </li></ul><ul><li>The number of plasma cells goes down after a few weeks </li></ul><ul><li>Antibodies stay in the blood longer but eventually their numbers go down too. </li></ul>
  24. 27. T-Lymphocytes <ul><li>CD3 in all types </li></ul><ul><li>CD4 in helper </li></ul><ul><li>CD8 in cytotoxic </li></ul>
  25. 29. Natural killer cells <ul><li>Large granular lymphocytes </li></ul><ul><li>Recognize and destroy cells bedaring viral or tumor surface markers </li></ul>
  26. 30. Complement <ul><li>Definition : series of heat-labile serum proteins </li></ul><ul><li>Site : serum and all tissue fluids except urine and CSF </li></ul><ul><li>Synthesis : in liver – appear in fetal circulation during 1 st 13 W </li></ul><ul><li>Function : Responsible for certain aspects of </li></ul><ul><li>immune response and inflammatory response </li></ul><ul><li>Activation : antigen-antibody complex or endotoxin, capsule </li></ul><ul><li>series of proteins activated sequentially </li></ul><ul><li>Inactivation: inhibitors in plasma (short lived) </li></ul>
  27. 31. Complement system <ul><li>Plasma protein sequence cascade </li></ul><ul><li>Triggered by </li></ul><ul><ul><li>Classic pathway </li></ul></ul><ul><ul><li>Alternative pathway </li></ul></ul><ul><ul><li>Lectin binding </li></ul></ul>Complement
  28. 32. Complement Activation <ul><li>Classical Pathway C 1 </li></ul><ul><li>C 4 C 2 </li></ul><ul><li>C 3 Alternative pathway </li></ul><ul><li>C 5 </li></ul><ul><li>C 6 </li></ul><ul><li>C 7 </li></ul><ul><li>C 8 </li></ul><ul><li>C 9 </li></ul><ul><li>Membrane damage </li></ul>
  29. 33. Classic And Alterenative pathways <ul><li>Classic Pathway Alternative pathway </li></ul><ul><li>* Specific acquired immunity * Non-specific innate immunity </li></ul><ul><li>* Initiated by antibody * Bacterial endotoxin, capsule </li></ul><ul><li>* Interaction of all components * C1, C4, C2 are by-passed </li></ul><ul><li>* Properdin system not involved * Properdin system is involved </li></ul>
  30. 34. Complement and disease <ul><li>Complement difficiency </li></ul><ul><li>Difficiency of classic pathway components </li></ul><ul><li>C3 difficiency </li></ul><ul><li>Terminal complement protein difficiencies </li></ul><ul><li>Difficiency of regulatory proteins </li></ul><ul><ul><li>Heriditary angioedema </li></ul></ul><ul><li>PNH </li></ul><ul><li>Complement consumption as in SLE </li></ul>
  31. 35. Functions of Complement <ul><li>Biologically active complement products have 3 main functions </li></ul><ul><li>Opsonisation …… C3b </li></ul><ul><li>Chemotaxis and inflammation……C3a, C5a </li></ul><ul><li>Cell lysis……….. C5,C6,C7,C8,C9 </li></ul>
  32. 36. Immunoglobulins
  33. 37. Classes of Immunoglobulines
  34. 38. Immunoglobulins & age
  35. 39. Plasma protein electrophoresis
  36. 40. Antigens <ul><li>Antigens are macromolecules that elicit an immune response in the body. The most common antigens are proteins and polysaccharides. </li></ul><ul><li>Hapten: incomplete Ag which can be conjugated with a carrier protein to form a complete Ag. </li></ul>
  37. 41. Cytokines <ul><li>hormone-like soluble low molecular weight protein molecules that act, generally in a paracrine fashion, to regulate immune responses </li></ul><ul><li>They are secreted not only by lymphocytes and macrophages but also by endothelial cells, adipocytes, neurons, glial cells, and other types of cells </li></ul>
  38. 42. Chemokines <ul><li>cytokines that regulate cell movement and trafficking; they attract neutrophils and other white blood cells to areas of inflammation or immune response. </li></ul>
  39. 43. Interferons <ul><li>are potent cytokines that possess antiviral, immunomodulating, and antiproliferative activities </li></ul><ul><li>Interferon- α , Interferon- β & Interferon- γ </li></ul><ul><li>Recombinant, natural, and pegylated IFNs currently are available for treatment of </li></ul><ul><ul><li>condyloma acuminatum, chronic HCV infection, chronic HBV infection, </li></ul></ul><ul><ul><li>Kaposi's sarcoma in HIV-infected patients, </li></ul></ul><ul><ul><li>other malignancies, </li></ul></ul><ul><ul><li>multiple sclerosis </li></ul></ul>
  40. 44. Tolerance <ul><li>It is a specific immunologic unresponsiveness </li></ul><ul><li>Unresponsiveness to self antigens is known as auto tolerance </li></ul>
  41. 45. Tolerance <ul><li>B-cells become tolerant to self by two mechanisms: </li></ul><ul><li>1) Clonal deletion </li></ul><ul><li>Probably while B-cell precursors are in bon marrow </li></ul><ul><li>2) Clonal anergy </li></ul><ul><li>B cells in the periphery </li></ul><ul><li>Tolerance in B-cells is less complete than in T-cells </li></ul><ul><li>The most autoimmune diseases are mediated by antibodies </li></ul>
  42. 46. Factors affecting induction of tolerance <ul><li>Maturity of the immune system </li></ul><ul><li>Antigen complexity </li></ul><ul><li>Antigen dose </li></ul><ul><li>Continuous presence of antigen </li></ul><ul><li>Immunosuppressive drugs </li></ul>
  43. 47. Clinical importance of tolerance <ul><li>Organ transplantation </li></ul><ul><li>Tumor development </li></ul><ul><li>Autoimmune diseases </li></ul>
  44. 48. Autoimmune Diseases <ul><li>Autoimmune diseases occur due to breakdown of the mechanisms that maintain auto tolerance </li></ul><ul><li>Auto-antibodies and self reactive T-cells are produced, resulting in tissue damage by several mechanisms </li></ul>
  45. 49. References <ul><li>Lecture notes: Immunology 2010 </li></ul><ul><li>Essential revision notes for MRCP 2009 </li></ul><ul><li>Merck manual : online textbook </li></ul><ul><li>Kumar & Klark : Clinical Medicine 2009 </li></ul><ul><li>Other Web Resources & books </li></ul>
  46. 50. Thank you
  47. 51. Understanding Immunology(2) Immunopathology
  48. 52. Immunodeficiency Immunopathology Autoimmunity Hypersensitivity Lymphoproliferative Diseases
  49. 53. References <ul><li>Lecture notes: Immunology 2010 </li></ul><ul><li>Essential revision notes for MRCP 2009 </li></ul><ul><li>Merck manual : online textbook </li></ul><ul><li>Kumar & Klark : Clinical Medicine 2009 </li></ul><ul><li>Other Web Resources & books </li></ul>
  50. 54. Thank you
  51. 55. Understanding Immunology (3) Therapeutic applications
  52. 56. References <ul><li>Lecture notes: Immunology 2010 </li></ul><ul><li>Essential revision notes for MRCP 2009 </li></ul><ul><li>Merck manual : online textbook </li></ul><ul><li>Kumar & Klark : Clinical Medicine 2009 </li></ul><ul><li>Other Web Resources & books </li></ul>
  53. 57. Thank you