This document summarizes different types of hypersensitivity reactions and immune disorders. It discusses type I, II, III, and IV hypersensitivity reactions, including their mechanisms, common examples, and symptoms. It also covers topics like transplantation, graft rejection, immunodeficiencies, cancer immunology, and various therapies.

1. Immune Disorders Chapter 21

2. Hypersensitivity HYPERSENSITIVITY IMMEDIATE DELAYED TYPE I Ig E - mediated TYPE II Cytotoxic TYPE III Immune Complex TYPE IV Cellular

3. Type I Hypersensitivity Is Induced by Allergens The sensitizing dose is the first dose of antigen The immune system responds as it would a pathogen The person is sensitized as IgE antibodies attach to mast cells and basophils Type 1 IgE-Mediated Hypersensitivity

4. Type 1 IgE-Mediated Hypersensitivity On subsequent allergen exposure, IgE antibodies are cross-linked This causes degranulation, which releases mediator substances: Histamine is released into the blood and causes smooth muscle cell constriction Leukotrienes are potent smooth muscle constrictors Prostaglandins can constrict bronchial tubes Cytokines can also stimulate/inhibit inflammation IL4, IL5, TNF-£

6. Is the Most Dangerous Form of a Type I Hypersensitivity Allergens in the bloodstream can trigger mast cell degranulation that contracts smooth muscle Small veins constrict and capillary pores expand, forcing fluid into the tissues A drop in blood pressure, edema, and rash occur Contractions in the gastrointestinal tract and bronchial muscles cause cramps and shortness of breath The lungs fill with carbon dioxide This can cause death by asphyxiation in 10-15 minutes Systemic Anaphylaxis Type 1 IgE-Mediated Hypersensitivity

7. Atopic Disorders Are the Most Common Form of a Type I Hypersensitivity Atopic disease is a common (seasonal) allergy caused by the inhalation of pollen Year-round allergies can result from chronic exposure to allergens Atopic Disorders Type 1 IgE-Mediated Hypersensitivity

8. Food allergies can cause symptoms like: swollen lips, abdominal cramps, nausea Diarrhea, hives (urticaria), anaphylaxis Involvement of eosinophils, neutrophils and T helper cells Physical factors that can cause allergies include: extreme temperatures, sunlight, sweating Exercise can cause allergies in the form of an asthma attack ECZEMA : atopic dermatitis; reddened skin rash with intense itching Atopic Disorders Type 1 IgE-Mediated Hypersensitivity

9. Allergic Reactions Also Are Responsible for Triggering Many Cases of Asthma Asthma can be caused by airborne allergens, exercise, or cold temperature Degranulation of mast cells releases mediators in the lower respiratory tract , causing: brochoconstriction vasodilation mucus buildup Recruitment of eosinophils and neutrophils into the lower respiratory tract can cause: tissue injury airway blockage Asthma Type 1 IgE-Mediated Hypersensitivity

10. Atopic people may lack sufficient IgA-secreting lymphocytes to block antigen stimulation in IgE Atopic people may have defective suppressor T cells, allowing for more IgE production Allergies may help expel pathogens through: sneezing gastrointestinal tract contractions Why Do Only Some People Have IgE-Mediated Hypersensitivities?

11. Desensitization therapy involves a series of injections of allergens which may: Cause gradual reduction of granules in sensitized mast cells Cause production of IgG antibodies that neutralize allergens (blocking antibodies) Monoclonal antibodies can be used to dislodge IgE from mast cells and basophils Antihistamines block the effect of histamine Corticosteroids are inhaled through the nose to relieve symptoms; some also block mediator release Therapies Sometimes Can Control Type I Hypersensitivities

13. Type II Cytotoxic Hypersensitivity Involves Antibody-Mediated Cell Destruction It occurs when IgG reacts with antigens, often activating complement Cell damaging reaction – Ig reacts with antigen on cell surface Cells affected are “target cells” TRANSFUSION REACTION Type II Cytotoxic Hypersensitivity

14. If incompatible blood types are mixed, agglutination occurs and complement is activated Rh disease can lead to stillbirth or jaundice Type II Cytotoxic Hypersensitivity

15. In myasthenia gravis , antibodies react with receptors on muscle fiber membranes, This causes a loss of muscle activity In Graves disease, antibodies bind unto thyroid gland cells This causes overproduction of thyroxine Hashimoto’s disease : antibodies attack thyroid gland cells leading to thyroxine deficiency In type I diabetes , pancreatic beta cells are destroyed A lack of insulin production results Type II Cytotoxic Hypersensitivity

16. THROMBOCYTOPENIA – results from antibodies produced against aspirin, antibiotics or antihistamines AGRANULOCYTOSIS – destruction of neutrophils by antibodies GOOD PASTURE SYNDROME – antibodies combine with antigens on the membranes of glomeruli in kidneys Type II Cytotoxic Hypersensitivity

17. Type III Immune Complex Hypersensitivity Is Caused by Antigen-Antibody Aggregates Develops when antibody combines with antigen and form aggregates that accumulate in the blood vessels or tissue surface Complement is activated (C3a and C5a) Type III

18. Serum sickness occurs when IgG is produced against residual proteins in a serum This can cause: kidney damage symptoms of type I anaphylactic hypersensitivity: hives and swelling in the face, neck and joints In the Arthus phenomenon , very large amounts of IgG complex with antigens This can lead to thromboses in blood vessels Type III Immune Complex Hypersensitivity

19. In systemic lupus erythematosus (a.k.a. SLE, lupus), nuclear components of disintegrating white blood cells elicit IgG production Immune complexes aggregate in the skin and organs, causing rash and lesions Rheumatoid arthritis (RA) is an inflammatory condition resulting in accumulation of immune complexes in joints Type III Immune Complex Hypersensitivity

20. Hemorrhagic shock – which may accompany dengue fever Subacute Sclerosing Panencephalitis – which follows a case of measles Lymphocytic Choriomeningitis – slow-forming kidney disease Type III Immune Complex Hypersensitivity

21. Is Mediated by Antigen-Specific T Cells Cellular hypersensitivity is an exaggeration of cell mediated immunity It is a delayed reaction characterized by: thickening and drying of skin tissue (induration) surrounding by erythema Infection allergy occurs when the immune system responds to certain microbial agents Sensitized lymphocytes remain in the tissue to provide immunity to subsequent infection Sensitivity can be determined by injection of a purified microbial sample and observation for induration (Mantoux test) Type IV Cellular Hypersensitivity

22. Contact dermatitis develops after exposure to a variety of allergens Repeated exposures cause drying to skin with erythema and scaling

23. Immunodeficiencies Can Involve Any Aspect of the Immune System Primary immunodeficiency is the result of a genetic abnormality Secondary immunodeficiency is acquired later in life Immunodeficiency Disorders

24. X-linked (Bruton) agammaglobulinemia is a congenital humoral immunodeficiency B cells fail to develop so patients lack mature B cells, plasma cells, and antibodies It is a sex-linked trait, more common in males than females In DiGeorge syndrome , the thymus fails to mature in the embryo so T cells do not develop Patients with ataxia-telangiectasia : have malfunctioning B and T cells are deficient in IgA and IgE Paralysis and dementia lead to death by age 30 Immunodeficiency Disorders

25. Severe combined immunodeficiency disease (SCID) involved lymph nodes deficient in B and T cells One form is caused by an enzyme deficiency that can be corrected using gene therapy In Chédiak-Higashi syndrome , lysosome within phagocytes cannot release their contents to kill microbes In chronic granulomatous disease, phagocytes do not produce substances to kill microbes Immunodeficiency Disorders

26. Transplantation of Tissues or Organs Is an Important Medical Therapy An autograft is a graft taken from one part of the body and transplanted to another part of the same body An isograft is a graft from one identical twin to the other twin Allografts are grafts between genetically different members of the same species Xenografts are grafts between members of different species (rarely successful) Transplantation

27. Rejection of transplants becomes more vigorous as the difference in genetic makeup of donor and recipient increases If the recipient body sees the transplanted tissue as “non-self,” the tissue is rejected Cytotoxic T cells attack and destroy transplanted cells Phagocytes secrete lysosomal enzymes that digest the tissue In bone marrow transplants, the transplanted marrow can form immune products against the host’s suppressed immune system Graft-versus-host-reaction (GVHR) can be fatal to the host Transplantation

28. MHC genes are believed to exist on chromosome 6 in humans 2 types of MHC proteins: Class I – nucleated cells Class II – important in the recognition of non self antigens when T lymphocytes combine with macrophages in CMI. The nature of MHC proteins is a key element in transplant acceptance or rejection. MHC and Transplant Rejection

29. Rejection is stimulated by recognition of MHC proteins on the surface of graft cells The closer the match between donor and recipient MHC proteins  the greater the chance of successful transplantation

30. Rejection is inhibited by immunosuppression in the host using: steroids that suppress the inflammatory response antilymphocyte antibodies antimitotic drugs drugs to suppress cell mediated immunity monoclonal antibodies radiation Transplantation

31. Four major immunotherapies: Chemotherapy and radiation Cytokines as immunostimulants Interferon alpha, IL – 2, TNF - £ Monoclonal antibodies Cancer vaccines Tumor Immunology