Chap21 Immune Disorders


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Chap21 Immune Disorders

  1. 1. Immune Disorders Chapter 21
  2. 2. Hypersensitivity HYPERSENSITIVITY IMMEDIATE DELAYED TYPE I Ig E - mediated TYPE II Cytotoxic TYPE III Immune Complex TYPE IV Cellular
  3. 3. <ul><li>Type I Hypersensitivity Is Induced by Allergens </li></ul><ul><ul><li>The sensitizing dose is the first dose of antigen </li></ul></ul><ul><ul><ul><li>The immune system responds as it would a pathogen </li></ul></ul></ul><ul><ul><li>The person is sensitized as IgE antibodies attach to mast cells and basophils </li></ul></ul>Type 1 IgE-Mediated Hypersensitivity
  4. 4. Type 1 IgE-Mediated Hypersensitivity <ul><li>On subsequent allergen exposure, IgE antibodies are cross-linked </li></ul><ul><li>This causes degranulation, which releases mediator substances: </li></ul><ul><ul><li>Histamine is released into the blood and causes smooth muscle cell constriction </li></ul></ul><ul><ul><li>Leukotrienes are potent smooth muscle constrictors </li></ul></ul><ul><ul><li>Prostaglandins can constrict bronchial tubes </li></ul></ul><ul><ul><li>Cytokines can also stimulate/inhibit inflammation </li></ul></ul><ul><ul><ul><li>IL4, IL5, TNF-£ </li></ul></ul></ul>
  5. 5.
  6. 6. <ul><li>Is the Most Dangerous Form of a Type I Hypersensitivity </li></ul><ul><li>Allergens in the bloodstream can trigger mast cell degranulation that contracts smooth muscle </li></ul><ul><li>Small veins constrict and capillary pores expand, forcing fluid into the tissues </li></ul><ul><ul><li>A drop in blood pressure, edema, and rash occur </li></ul></ul><ul><li>Contractions in the gastrointestinal tract and bronchial muscles cause cramps and shortness of breath </li></ul><ul><li>The lungs fill with carbon dioxide </li></ul><ul><ul><li>This can cause death by asphyxiation in 10-15 minutes </li></ul></ul>Systemic Anaphylaxis Type 1 IgE-Mediated Hypersensitivity
  7. 7. <ul><li>Atopic Disorders Are the Most Common Form of a Type I Hypersensitivity </li></ul><ul><ul><li>Atopic disease is a common (seasonal) allergy caused by the inhalation of pollen </li></ul></ul><ul><ul><li>Year-round allergies can result from chronic exposure to allergens </li></ul></ul>Atopic Disorders Type 1 IgE-Mediated Hypersensitivity
  8. 8. <ul><li>Food allergies can cause symptoms like: </li></ul><ul><ul><li>swollen lips, abdominal cramps, nausea </li></ul></ul><ul><ul><li>Diarrhea, hives (urticaria), anaphylaxis </li></ul></ul><ul><li>Involvement of eosinophils, neutrophils and T helper cells </li></ul><ul><li>Physical factors that can cause allergies include: extreme temperatures, sunlight, sweating </li></ul><ul><li>Exercise can cause allergies in the form of an asthma attack </li></ul><ul><li>ECZEMA : atopic dermatitis; reddened skin rash with intense itching </li></ul>Atopic Disorders Type 1 IgE-Mediated Hypersensitivity
  9. 9. <ul><li>Allergic Reactions Also Are Responsible for Triggering Many Cases of Asthma </li></ul><ul><li>Asthma can be caused by airborne allergens, exercise, or cold temperature </li></ul><ul><li>Degranulation of mast cells releases mediators in the lower respiratory tract , causing: </li></ul><ul><ul><li>brochoconstriction </li></ul></ul><ul><ul><li>vasodilation </li></ul></ul><ul><ul><li>mucus buildup </li></ul></ul><ul><li>Recruitment of eosinophils and neutrophils into the lower respiratory tract can cause: </li></ul><ul><ul><li>tissue injury </li></ul></ul><ul><ul><li>airway blockage </li></ul></ul>Asthma Type 1 IgE-Mediated Hypersensitivity
  10. 10. <ul><li>Atopic people may lack sufficient IgA-secreting lymphocytes to block antigen stimulation in IgE </li></ul><ul><li>Atopic people may have defective suppressor T cells, allowing for more IgE production </li></ul><ul><li>Allergies may help expel pathogens through: </li></ul><ul><ul><li>sneezing </li></ul></ul><ul><ul><li>gastrointestinal tract contractions </li></ul></ul>Why Do Only Some People Have IgE-Mediated Hypersensitivities?
  11. 11. <ul><li>Desensitization therapy involves a series of injections of allergens which may: </li></ul><ul><ul><ul><li>Cause gradual reduction of granules in sensitized mast cells </li></ul></ul></ul><ul><ul><ul><li>Cause production of IgG antibodies that neutralize allergens (blocking antibodies) </li></ul></ul></ul><ul><li>Monoclonal antibodies can be used to dislodge IgE from mast cells and basophils </li></ul><ul><li>Antihistamines block the effect of histamine </li></ul><ul><li>Corticosteroids are inhaled through the nose to relieve symptoms; some also block mediator release </li></ul>Therapies Sometimes Can Control Type I Hypersensitivities
  12. 12.
  13. 13. <ul><li>Type II Cytotoxic Hypersensitivity Involves Antibody-Mediated Cell Destruction </li></ul><ul><ul><li>It occurs when IgG reacts with antigens, often activating complement </li></ul></ul><ul><ul><li>Cell damaging reaction – Ig reacts with antigen on cell surface </li></ul></ul><ul><ul><li>Cells affected are “target cells” </li></ul></ul><ul><ul><li>TRANSFUSION REACTION </li></ul></ul>Type II Cytotoxic Hypersensitivity
  14. 14. <ul><li>If incompatible blood types are mixed, agglutination occurs and complement is activated </li></ul><ul><ul><li>Rh disease can lead to stillbirth or jaundice </li></ul></ul>Type II Cytotoxic Hypersensitivity
  15. 15. <ul><li>In myasthenia gravis , antibodies react with receptors on muscle fiber membranes, </li></ul><ul><ul><li>This causes a loss of muscle activity </li></ul></ul><ul><li>In Graves disease, antibodies bind unto thyroid gland cells </li></ul><ul><ul><li>This causes overproduction of thyroxine </li></ul></ul><ul><li>Hashimoto’s disease : antibodies attack thyroid gland cells leading to thyroxine deficiency </li></ul><ul><li>In type I diabetes , pancreatic beta cells are destroyed </li></ul><ul><ul><li>A lack of insulin production results </li></ul></ul>Type II Cytotoxic Hypersensitivity
  16. 16. <ul><li>THROMBOCYTOPENIA – results from antibodies produced against aspirin, antibiotics or antihistamines </li></ul><ul><li>AGRANULOCYTOSIS – destruction of neutrophils by antibodies </li></ul><ul><li>GOOD PASTURE SYNDROME – antibodies combine with antigens on the membranes of glomeruli in kidneys </li></ul>Type II Cytotoxic Hypersensitivity
  17. 17. <ul><li>Type III Immune Complex </li></ul><ul><li>Hypersensitivity Is Caused by </li></ul><ul><li>Antigen-Antibody Aggregates </li></ul><ul><li>Develops when antibody combines with antigen and form aggregates that accumulate in the blood vessels or tissue surface </li></ul><ul><li>Complement is activated (C3a and C5a) </li></ul>Type III
  18. 18. <ul><li>Serum sickness occurs when IgG is produced against residual proteins in a serum </li></ul><ul><ul><li>This can cause: </li></ul></ul><ul><ul><ul><li>kidney damage </li></ul></ul></ul><ul><ul><ul><li>symptoms of type I anaphylactic hypersensitivity: hives and swelling in the face, neck and joints </li></ul></ul></ul><ul><li>In the Arthus phenomenon , very large amounts of IgG complex with antigens </li></ul><ul><ul><li>This can lead to thromboses in blood vessels </li></ul></ul>Type III Immune Complex Hypersensitivity
  19. 19. <ul><li>In systemic lupus erythematosus (a.k.a. SLE, lupus), nuclear components of disintegrating white blood cells elicit IgG production </li></ul><ul><ul><li>Immune complexes aggregate in the skin and organs, causing rash and lesions </li></ul></ul><ul><li>Rheumatoid arthritis (RA) is an inflammatory condition resulting in accumulation of immune complexes in joints </li></ul>Type III Immune Complex Hypersensitivity
  20. 20. <ul><li>Hemorrhagic shock – which may accompany dengue fever </li></ul><ul><li>Subacute Sclerosing Panencephalitis – which follows a case of measles </li></ul><ul><li>Lymphocytic Choriomeningitis – slow-forming kidney disease </li></ul>Type III Immune Complex Hypersensitivity
  21. 21. <ul><li>Is Mediated by Antigen-Specific T Cells </li></ul><ul><li>Cellular hypersensitivity is an exaggeration of cell mediated immunity </li></ul><ul><li>It is a delayed reaction characterized by: </li></ul><ul><ul><li>thickening and drying of skin tissue (induration) </li></ul></ul><ul><ul><li>surrounding by erythema </li></ul></ul><ul><li>Infection allergy occurs when the immune system responds to certain microbial agents </li></ul><ul><ul><li>Sensitized lymphocytes remain in the tissue to provide immunity to subsequent infection </li></ul></ul><ul><ul><li>Sensitivity can be determined by injection of a purified microbial sample and observation for induration (Mantoux test) </li></ul></ul>Type IV Cellular Hypersensitivity
  22. 22. <ul><li>Contact dermatitis develops after exposure to a variety of allergens </li></ul><ul><ul><li>Repeated exposures cause drying to skin with erythema and scaling </li></ul></ul>
  23. 23. <ul><li>Immunodeficiencies Can Involve Any Aspect of the Immune System </li></ul><ul><ul><li>Primary immunodeficiency is the result of a genetic abnormality </li></ul></ul><ul><ul><li>Secondary immunodeficiency is acquired later in life </li></ul></ul>Immunodeficiency Disorders
  24. 24. <ul><li>X-linked (Bruton) agammaglobulinemia is a congenital humoral immunodeficiency </li></ul><ul><ul><li>B cells fail to develop so patients lack mature B cells, plasma cells, and antibodies </li></ul></ul><ul><ul><li>It is a sex-linked trait, more common in males than females </li></ul></ul><ul><li>In DiGeorge syndrome , the thymus fails to mature in the embryo so T cells do not develop </li></ul><ul><li>Patients with ataxia-telangiectasia : </li></ul><ul><ul><li>have malfunctioning B and T cells </li></ul></ul><ul><ul><li>are deficient in IgA and IgE </li></ul></ul><ul><ul><li>Paralysis and dementia lead to death by age 30 </li></ul></ul>Immunodeficiency Disorders
  25. 25. <ul><li>Severe combined immunodeficiency disease (SCID) involved lymph nodes deficient in B and T cells </li></ul><ul><ul><li>One form is caused by an enzyme deficiency that can be corrected using gene therapy </li></ul></ul><ul><li>In Chédiak-Higashi syndrome , lysosome within phagocytes cannot release their contents to kill microbes </li></ul><ul><li>In chronic granulomatous disease, phagocytes do not produce substances to kill microbes </li></ul>Immunodeficiency Disorders
  26. 26. <ul><li>Transplantation of Tissues or Organs Is an Important Medical Therapy </li></ul><ul><ul><li>An autograft is a graft taken from one part of the body and transplanted to another part of the same body </li></ul></ul><ul><ul><li>An isograft is a graft from one identical twin to the other twin </li></ul></ul><ul><ul><li>Allografts are grafts between genetically different members of the same species </li></ul></ul><ul><ul><li>Xenografts are grafts between members of different species (rarely successful) </li></ul></ul>Transplantation
  27. 27. <ul><li>Rejection of transplants becomes more vigorous as the difference in genetic makeup of donor and recipient increases </li></ul><ul><li>If the recipient body sees the transplanted tissue as “non-self,” the tissue is rejected </li></ul><ul><ul><li>Cytotoxic T cells attack and destroy transplanted cells </li></ul></ul><ul><ul><li>Phagocytes secrete lysosomal enzymes that digest the tissue </li></ul></ul><ul><li>In bone marrow transplants, the transplanted marrow can form immune products against the host’s suppressed immune system </li></ul><ul><ul><li>Graft-versus-host-reaction (GVHR) can be fatal to the host </li></ul></ul>Transplantation
  28. 28. <ul><li>MHC genes are believed to exist on chromosome 6 in humans </li></ul><ul><li>2 types of MHC proteins: </li></ul><ul><ul><li>Class I – nucleated cells </li></ul></ul><ul><ul><li>Class II – important in the recognition of non self antigens when T lymphocytes combine with macrophages in CMI. </li></ul></ul><ul><li>The nature of MHC proteins is a key element in transplant acceptance or rejection. </li></ul>MHC and Transplant Rejection
  29. 29. <ul><li>Rejection is stimulated by recognition of MHC proteins on the surface of graft cells </li></ul><ul><ul><li>The closer the match between donor and recipient MHC proteins  the greater the chance of successful transplantation </li></ul></ul>
  30. 30. <ul><li>Rejection is inhibited by immunosuppression in the host using: </li></ul><ul><ul><li>steroids that suppress the inflammatory response </li></ul></ul><ul><ul><li>antilymphocyte antibodies </li></ul></ul><ul><ul><li>antimitotic drugs </li></ul></ul><ul><ul><li>drugs to suppress cell mediated immunity </li></ul></ul><ul><ul><li>monoclonal antibodies </li></ul></ul><ul><ul><li>radiation </li></ul></ul>Transplantation
  31. 31. <ul><li>Four major immunotherapies: </li></ul><ul><ul><li>Chemotherapy and radiation </li></ul></ul><ul><ul><li>Cytokines as immunostimulants </li></ul></ul><ul><ul><ul><li>Interferon alpha, IL – 2, TNF - £ </li></ul></ul></ul><ul><ul><li>Monoclonal antibodies </li></ul></ul><ul><ul><li>Cancer vaccines </li></ul></ul>Tumor Immunology