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Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
Immunology 1, 2, 3
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Immunology 1, 2, 3

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Understanding Immunology for internists

Understanding Immunology for internists

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  • 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
  • 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>
  • 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
  • 5. Immunity
  • 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>
  • 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>
  • 8.  
  • 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>
  • 10. Innate Adaptive Immunity Cellular Humoral Cellular Humoral Let us see this video about immunity
  • 11. Inflammation <ul><li>Inflammation is a nonspecific response of living tissue to localize and eliminate the injurious agent </li></ul>Immune Response
  • 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>
  • 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>
  • 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>
  • 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>
  • 16.  
  • 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>
  • 18. Cells of the immune system T-cell development
  • 19. Cells of the immune system
  • 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>
  • 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>
  • 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>
  • 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>
  • 24. Phagocytosis
  • 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>
  • 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>
  • 27. T-Lymphocytes <ul><li>CD3 in all types </li></ul><ul><li>CD4 in helper </li></ul>
  • 28.  
  • 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>
  • 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>
  • 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
  • 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>
  • 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>
  • 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>
  • 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>
  • 36. Immunoglobulins
  • 37. Classes of Immunoglobulines
  • 38. Immunoglobulins & age
  • 39. Plasma protein electrophoresis
  • 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>
  • 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>
  • 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>
  • 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>
  • 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>
  • 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>
  • 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>
  • 47. Clinical importance of tolerance <ul><li>Organ transplantation </li></ul><ul><li>Tumor development </li></ul><ul><li>Autoimmune diseases </li></ul>
  • 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>
  • 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>
  • 50. Thank you
  • 51. Understanding Immunology(2) Immunopathology
  • 52. Immunodeficiency Immunopathology Autoimmunity Hypersensitivity Lymphoproliferative Diseases
  • 53. Immunodeficiency
  • 54. Acquired Immunodeficiency <ul><li>Infections </li></ul><ul><li>Drugs and toxins </li></ul><ul><li>Radiation </li></ul><ul><li>Malignancy </li></ul><ul><li>Malnutrition , Diabetes & Renal failure </li></ul><ul><li>Splenectomy & Thymectomy </li></ul><ul><li>Aging </li></ul><ul><li>Stress </li></ul>
  • 55. HIV/AIDS <ul><li>Infects T-helper cells </li></ul><ul><li>Progressive decline in CD4 counts </li></ul><ul><li>Impaired cell mediated immunity </li></ul><ul><li>Associated polyclonal activation of B-cells and hypergamaglobulinemia </li></ul>
  • 56. Immune response to HIV
  • 57. CD4 depletion along the course of HIV
  • 58. Primary immunodeficiency <ul><li>Immune system not fully developed until at least two years of age. </li></ul><ul><li>Immuno-competent kids may have up to six URIs per year. Ten URIs per year if they attend daycare. </li></ul><ul><li>Risk Factors for Frequent Infections </li></ul><ul><li>When to suspect? </li></ul>
  • 59. Complement deficiencies Immunodeficiency B-cell disorders Neutrophil Disorders T-cell disorders Combined B and T-cell disorders
  • 60. Neutrophil disorders <ul><li>Chronic granulomatous disease </li></ul><ul><li>Chediak-Higashi disease </li></ul><ul><li>Hyper Ig-E syndrome </li></ul><ul><li>Myeloperoxidase deficiency </li></ul><ul><li>Lazy Leukocyte Syndrome </li></ul><ul><li>Leukocyte adhesion deficiency </li></ul>
  • 61. Lymphocyte disorders
  • 62. B-cell disorders <ul><li>IgA deficiency </li></ul><ul><li>Common variable immunodeficiency </li></ul><ul><li>Bruton’s X-linked agamaglobulinemia( no circulating B-cells) </li></ul>
  • 63. T-cell disorders <ul><li>Digeorge syndrome </li></ul><ul><li>Nezelof syndrome </li></ul><ul><li>Purine nucleoside phosphorylase deficiency </li></ul>
  • 64. Combined B- and T-cell disorders <ul><li>Severe combined immunodeficiency </li></ul><ul><li>Reticular dysgenesis </li></ul><ul><li>Ataxia telangiectasia </li></ul><ul><li>Wiskott-Aldrich syndrome </li></ul>
  • 65. Diagnosis of primary immunodeficiency <ul><li>History </li></ul><ul><li>Examination </li></ul><ul><li>Investigations of the immune system </li></ul>
  • 66. Clinical history
  • 67. Disease Specific Skin Findings <ul><li>Eczema and petechiae – Wiskott-Aldrich Syndrome </li></ul><ul><li>Telangiectasia – Ataxia-Telangiectasia </li></ul><ul><li>Oculocutaneous albinism – Chediak-Higashi </li></ul><ul><li>Dermatomyositis-like rash – XLA </li></ul><ul><li>Chronic dermatitis – Hyper-IgE </li></ul><ul><li>Generalized molluscum, extensive warts, candidiasis – T-Cell defects </li></ul>
  • 68. 2- Autoimmunity
  • 69.  
  • 70. Type-1 diabetes
  • 71. Etiology of autoimmune diseases <ul><li>Genetic predisposition </li></ul><ul><li>Cross reactivity </li></ul><ul><li>Alteration of self antigens </li></ul><ul><li>Hormonal influences </li></ul>
  • 72. Mechanisms Of Disease Production in autoimmunity <ul><li>1) Binding of an autoantibody to host cells result in complement fixation and tissue destruction </li></ul><ul><li>e.g. Haemolytic anemia (Type II hypersensitivity) </li></ul><ul><li>2) Formation of immune complexes and their </li></ul><ul><li>deposition in tissues, joints, kidney and skin </li></ul><ul><li>The immune complexes fix complement resulting in </li></ul><ul><li>tissue damage e.g. SLE and rheumatoid arthritis (Type III hyper.) </li></ul><ul><li>3) DTH reactions (Type IV)) due to auto reactive T-cells </li></ul><ul><li>e.g. Ulcerative colitis, multiple sclerosis and </li></ul><ul><li>type I diabetes </li></ul>
  • 73. Auto-antibodies <ul><li>ANA </li></ul><ul><li>Anti-dsDNA </li></ul><ul><li>Anti-smith </li></ul><ul><li>RF </li></ul><ul><li>Anti-Ro </li></ul><ul><li>Anti-La </li></ul><ul><li>ANCA </li></ul><ul><li>ASMA </li></ul><ul><li>Anti-mitochondrial </li></ul>
  • 74. Transplacental transfer
  • 75. 3- Allergy and Hypersensitivity <ul><li>Immune responses with undesirable consequences </li></ul><ul><li>5 Types </li></ul><ul><li>Type I: Anaphylactic or immediate </li></ul><ul><li>Type II:Antibody dependant cytotoxcicity </li></ul><ul><li>Type III:Immune complex mediated or Arthus </li></ul><ul><li>TypeIV: Cell mediated or delayed </li></ul><ul><li>Type V: Stimulatory </li></ul>
  • 76.  
  • 77. 4- Malignancies of the immune system <ul><li>Lymphocytosis and lymphadenopathy </li></ul><ul><li>Leukemias </li></ul><ul><li>Lymphomas </li></ul><ul><li>Mylomas and monoclonal gammopathies </li></ul>
  • 78. Hodgkin's disease
  • 79. Immunity and cancer <ul><li>Tumor immunology </li></ul><ul><li>Tumor antigens </li></ul><ul><li>Immune surveillance system </li></ul><ul><li>Tumor escape from immune surveillance </li></ul>
  • 80. Tumor Markers <ul><li>* Tumor markers : </li></ul><ul><li>Tumor antigens </li></ul><ul><li>* They are either or </li></ul><ul><li>Tumor products </li></ul><ul><li>(enzymes and hormones) </li></ul><ul><li>* Tumor products are released in the serum of patients </li></ul><ul><li>* They are used to confirm diagnosis and follow up the response to therapy </li></ul>
  • 81. Tumor Antigens <ul><li>1) Alpha fetoprotein antigen (AFP) in cases of hepatoma </li></ul><ul><li>2) Carcinoembryoinic antigen (CEA) in gastrointestinal tumors, tumors of biliary system and cancer breast </li></ul><ul><li>3) Cancer antigen 125 (CA 125) in ovarian carcinoma </li></ul><ul><li>4) Cancer antigen 15-3 (CA15-3) in breast cancer </li></ul><ul><li>5) Cancer antigen 19-9 in colon and pancreatic tumor </li></ul><ul><li>6) Prostatic specific antigen (PSA) in prostatic tumors </li></ul>
  • 82. Tumor Products <ul><li>a) Hormones : </li></ul><ul><li>- Human chorionic gonadotrophins (HCG) are secreted </li></ul><ul><li>in cases of choriocarcinoma </li></ul><ul><li>- Thyroxin (T3 & T4) is secreted in cases of cancer </li></ul><ul><li>of thyroid gland </li></ul><ul><li>b) Enzymes : </li></ul><ul><li>- Acid phosphatase enzymes in cases of cancer prostae </li></ul><ul><li>- Alkaline phosphatese, lipase and amylase enzymes in cases of cancer pancreas </li></ul>
  • 83. 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>
  • 84. Thank you
  • 85. Understanding Immunology (3) Therapeutic applications
  • 86. Immunization Therapeutic applications of Immunology Immunomodulation Transplantation Immunosupression Anti-allergic Replacement
  • 87. Immunization <ul><li>Passive immunization </li></ul><ul><li>Active immunization </li></ul>
  • 88. History of immunization <ul><li>1721---------Variolation </li></ul><ul><li>1796---------vaccination </li></ul><ul><li>1885--------- Rabies </li></ul><ul><li>1925--------- Toxoids </li></ul><ul><li>1954---------Salk </li></ul><ul><li>1956---------Sabin </li></ul><ul><li>1975--------- hepatitis B </li></ul><ul><li>1995--------- hepatitis A </li></ul><ul><li>2007---------- HPV </li></ul>
  • 89. Types of vaccines <ul><li>Killed vaccines </li></ul><ul><ul><ul><li>Salk , pertussis, typhoid, rabies </li></ul></ul></ul><ul><li>Live attenuated vaccines </li></ul><ul><ul><ul><li>BCG, sabin, rubella, measles, mumps </li></ul></ul></ul><ul><li>Subunit vaccines </li></ul><ul><ul><ul><li>Hepatitis B, H influenza, strept pneumonia </li></ul></ul></ul>
  • 90. No satisfactory vaccine for <ul><li>HIV, HCV </li></ul><ul><li>Herpes viruses </li></ul><ul><li>Rhinoviruses </li></ul><ul><li>T.B </li></ul><ul><li>Leprosy </li></ul><ul><li>Cholera </li></ul><ul><li>Parasites </li></ul>
  • 91. Pneumococcal vaccination <ul><li>INDICATIONS: </li></ul><ul><ul><li>Primary vaccination (conjugate vaccine) </li></ul></ul><ul><ul><li>children 2 yr. or older with </li></ul></ul><ul><ul><ul><li>Anatomical or functional asplenia </li></ul></ul></ul><ul><ul><ul><li>Sickle cell disease </li></ul></ul></ul><ul><ul><ul><li>Nephrotic syndrome </li></ul></ul></ul><ul><ul><ul><li>Immunosuppression </li></ul></ul></ul>
  • 92. Contraindications of vaccines <ul><li>Moderate or severe illness with or without fever </li></ul><ul><li>Anaphylactic reaction to vaccine or vaccine constituent </li></ul><ul><li>Live attenuated vaccines </li></ul><ul><ul><li>Pregnant women </li></ul></ul><ul><ul><li>Immunocompromised / Immunosuppressed children </li></ul></ul><ul><ul><li>within 3-11 months of immunoglobulin administration </li></ul></ul>
  • 93. Invalid contraindications to vaccines <ul><li>Mild to moderate local reaction </li></ul><ul><li>Mild acute illness with or without low grade fever </li></ul><ul><li>Current antimicrobial therapy </li></ul><ul><li>Convalescent phase of illnesses </li></ul><ul><li>Prematurity and low birth weight </li></ul><ul><li>History of penicillin or other nonspecific allergies </li></ul><ul><li>Malnutrition </li></ul>
  • 94. Types of grafts <ul><li>Autografts </li></ul><ul><li>Isografts </li></ul><ul><li>Allografts (homograft): </li></ul><ul><li>Xenograft (heterograft): </li></ul>
  • 95. Major Histocompatibility Complex (MHC) <ul><li>The MHC is a closely linked complex of genes that govern production of the major histocompatibility </li></ul><ul><li>In humans, MHC resides on the short arm of chromosome 6 </li></ul><ul><li>Three genes (HLA-A, HLA-B, HLA-C) code for the class I MHC proteins </li></ul><ul><li>Several HLA-D loci determine the class II MHC proteins i.e. DP, DQ and DR </li></ul><ul><li>HLA genes are very diverse (polymorphic)i.e. there are many alleles of the class I and II genes </li></ul>
  • 96. Class III MHC <ul><li>Between the class I and class II gene loci, there is a third locus (Class III) </li></ul><ul><li>This locus contains genes encoding tumor necrosis factor, lymphotoxin and two complement components (C2 and C4) </li></ul><ul><li>Class III antigens do not participate in MHC restriction or graft rejection </li></ul>
  • 97. MHC I & II CD4 TH cells CD8 TC cells Recognized by Presentation of Ag to TH cells which secrete cytokines Presentation of Ag to TC cells leading to elimination of tumor or infected host cell Functions Macrophages, B-cells, Dentritic cells, langerhans cells of skin and activated T cells All nucleated somatic cells Found on HLA-DP, HLA-DQ, HLA-DR HLA-A, HLA-B, HLA-C Nomenclature MHC Class II MHC Class I
  • 98. MHC and antigen presentation <ul><li>T-cells are only activated when they recognize both antigen and class I MHC molecules in association </li></ul><ul><li>Helper T-cells recognize antigens on antigen-presenting cells only when the antigens are presented on the surface of cells in association with class II MHC </li></ul>
  • 99. Matching with donors <ul><li>HLA DR and HLA B in the kidney </li></ul><ul><li>Heart and liver survive well with immunosupression </li></ul>
  • 100. Types of rejection <ul><li>Hyperacute rejection </li></ul><ul><li>Acute Rejection </li></ul><ul><li>Acute late </li></ul><ul><li>Chronic or late rejection </li></ul>
  • 101. Graft Versus Host reaction (GVH) <ul><li>An immunologically competent graft is transplanted into an immunologically suppressed recipient (host) </li></ul><ul><li>The grafted cells survive and react against the host cells i.e instead of reaction of host against the graft, the reverse occurs </li></ul><ul><li>GVH reaction is characterized by fever, pancytopenia, weight loss, rash , diarrhea, hepatsplenomegaly and death </li></ul>
  • 102. Immunosupression <ul><li>Calcineurin inhibitors </li></ul><ul><li>Azathioprin </li></ul><ul><li>Methotrexate </li></ul><ul><li>Cyclophosphamide </li></ul>
  • 103. Replacement therapy <ul><li>IV IG </li></ul><ul><li>C1 estrase </li></ul>
  • 104. IG therapy <ul><li>IV </li></ul><ul><li>SC </li></ul><ul><li>Indications </li></ul><ul><li>Side effects </li></ul>
  • 105. Antibodies as drugs <ul><li>Infliximab </li></ul><ul><li>Etanercept </li></ul><ul><li>Anakinra </li></ul><ul><li>Rutiximab </li></ul><ul><li>Abciximab </li></ul><ul><li>Digibind </li></ul><ul><li>Natalizumab </li></ul>
  • 106. Nomenclature of monoclonal abs toxin as target -tox(a)- nervous system -neu(r)- miscellaneous tumor -tu(m)- prostate tumor -pr(o)- ovarian tumor -go(v)- testicular tumor -go(t)- mammary tumor -ma(r)- melanoma -me(l)- colonic tumor -co(l)- rat/murine hybrid -axo- interleukin -ki(n)- humanized -zu- musculoskeletal -mu(l)- chimeric -xi- cardiovascular -ci(r)- primate -i- infectious lesions -le(s)- hamster -e- immune -li(m)- rat -a- bacterial -ba(c)- mouse -o- viral -vi(r)- -mab human -u- bone -o(s)- variable Suffix Source Target Prefix
  • 107. Rutiximab( anti CD-20) <ul><li>Rituxan® by Genentech </li></ul><ul><li>Anti-B cell (CD20) antibody </li></ul><ul><li>First approved in 1997 for use in B-cell lymphoma </li></ul><ul><li>Given in combination with Methotrexate </li></ul><ul><li>Directed for patients who do not respond to Anti-TNF treatments </li></ul><ul><li>Indicates the rheumatoid arthritis has a B cell component to its pathology </li></ul>
  • 108. Desensitization <ul><li>In ttt of allergic conditions </li></ul>
  • 109. Anti-allergic drugs <ul><li>Antihistamines </li></ul><ul><li>Mast cell stabilizers </li></ul><ul><li>others </li></ul>
  • 110. Immunotherapy for cancer <ul><li>Pathogen vaccines </li></ul><ul><li>Tumor vaccines </li></ul><ul><li>others </li></ul>
  • 111. 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>
  • 112. Thank you

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