Immune System Disorders

1. Immune System Disorders Hypersensitivities (≈ Allergies) I) Anaphalactic II) Cytotoxic III) Immune Complex IV) Cell-mediated (Delayed) Autoimmune Diseases Transplant Rejection Hypersensitivity results from a second exposure to what could be normally harmless antigen (≈ allergen). The second response is not an appropriate normal one. The immune system goes too far.

2. I) Anaphalaxis Allergies to pollen, pet dander, insect venoms, fungal spores, dust mites, peanuts, & penicillin. Localized: (asthma, allergic rhinitis; true food allergies) Systemic (anaphalactic shock): vasodilation throughout body, BP drops; capillaries become porous; edema; constricts brachioles; fatality. IgE from first exposure to antigen (≈ allergen) bind to mast cells and basophils; the person is “sensitized”.

4. Treatment of Anaphalaxis • Short-Term: • anti-histamines; epinephrine • leukotriene receptor blockers • Long-Term: • - Controlled repeat exposures; boost IgG

5. II) Cytotoxic • IgG and IgM antibodies bind to foreign antigens on the surface of otherwise healthy human blood cell types. • This results in activation of the complement cascade via the classic pathway, which leads to cytolysis of blood cells with the foreign antigen. • Further antibody and complement C3b binding results in opsonization (i.e. enhanced phagocytosis by phagocytes) of the blood cells with the foreign antigen. • Which foreign antigens will cause a cytotoxic reaction? • AB red blood cell (RBC) antigens & Rh RBC antigen • Drugs (haptens) that bind to blood platelets to become antigenic.

6. Transfusion Rh Incompatibility & Hemolytic Disease of the Newbornes

7. Thrombocytopenic purpura = thrombocyte Intracerebral hemorrhaging Stroke Bruising due to low platelet count; poor clotting favors hemorrhages.

8. III) Immune Complex The right proportions of antigen to IgG antibody results in small immune complexes avoid phagocytosis and instead get stuck beneath endothelial cells of capillaries. Damaging to kidney glomeruli (glomerulonephritis).

9. IV) Cell-Mediated (Delayed) Takes days not hours or minutes; requires T cell and macrophage migration to foreign antigen exposure sight. Allergic Contact Dermatitis: Latex gloves Poison ivy TB skin test is cell-mediated.

10. Autoimmune Diseases • Lymphocytes become involved in attacking the bodies own cells (antigens). • Self-tolerance of lymphocytes is lost: B cells produce antibodies and Tc cells activate their cytotoxicity. Causes: • Similarities between viral and self antigens (Hepitius C autoimmunity). • Cell malfunction due to antibody binding (Grave’s Disease; thyroid gland). • Immune complex forms (rheumatoid arthritis; joints). • Cell-mediated destruction of specific cell types (insulin-dependent diabetes mellitus; insulin-secreting cells of pancreas). • Some individuals are genetically predisposed (higher risk) due to specific human leukocyte antigen (HLA) gene alleles that they possess.

11. Transplant Rejection • Non-self hypothesis: for most tissues if the HLA classes do not match there will be rejections by T cell, antibody, and complement attack on transplant blood vessels; see graft-versus-host (GVH) disease. • This does not apply for privileged sites; those that are non-vascular (cornea, heart valves); rare exceptions. • Grafts are the new tissues transplanted to a target site. • Autographs; • isographs; • allographs; and • xenographs. • Immunosuppression by cyclosporine to minimize transplant rejection; its action is suppression of IL-2 release. Other IL-2 receptor blockers are also available (rapamycin).