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Disorders in ImmunityHypersensitivities, Autoimmune diseases and Deficiencies Chapter 18
Immunopathology • Underreaction/Overreaction • Allergy, hypersensitivity – an exaggerated, misdirected expression of immune responses • Involves the same types of immune reactions as those at work in protective immunities. • Autoimmunity – abnormal responses to self Ag • Immunodeficiency – deficiency or loss of immunity
Type I Hypersensitivity(immediate hypersensitivity) • Atopy – any chronic local allergy such as hay fever or asthma • Anaphylaxis – a systemic, often explosive reaction that involves airway obstruction and circulatory collapse
Type I Hypersensitivity (atopy) • Allergic Rhinitis (hay fever) (35 million Americans?) • Asthma (2 million Americans?) • A predisposition toward allergies can be inherited. • Food allergy • Drug allergy • Atopic dermatitis (eczema) …”the itch that rashes”
Eczema Eczema is a general term encompassing various inflamed skin conditions. One of the most common forms of eczema is atopic dermatitis. Characterized by dry, red, extremely itchy patches on the skin. Eczema is sometimes referred to as "the itch that rashes," since the itch, when scratched, results in the appearance of the rash. Eczema occurs in both children and adults, but usually appears during infancy. Often affects people with a family history of allergies. There may be multiple causes
Systemic Anaphylaxis • Sudden respiratory and circulatory disruption that can be fatal in a few minutes • Bee stings, antibiotics or serum injection
Mechanism of Type I • sensitizing dose – on first contact with allergen, specific B cells form IgE which attaches to mast cells and basophils • provocativedose - subsequent exposure with the same allergen binds to the IgE-mast cell complex • degranulation releases mediators with physiological effects such as vasodilation and bronchoconstriction • symptoms are rash, itching, redness, increased mucous discharge, pain, swelling, and difficulty breathing
Role of Mast Cells & Basophils • Mast cells are located in the connective tissue of virtually all organs; high conc. in lungs, skin, GI and genital tract • Basophils circulate in blood, migrate into tissues • each cell can bind 10,000-40,000 IgE • cytoplasmic granules contain chemical mediators. (cytokines, histamine, etc) • cells degranulate when stimulated by allergen
Chemical mediators • Cytokines • Histamine • Serotonin • Prostaglandins • Bradykinin • Leukotriene
Allergy Testing Skin testing
Allergy Therapy • Desensitization / Hyposensitization • Avoidance • Drugs
Type II Hypersensitivity(cytotoxic hypersensitivity) • Reactions that lyse foreign cells • Involve antibodies, complement, leading to lysis of foreign cells • Transfusion reactions • ABO blood groups • Rh factor – hemolytic disease of the newborn
Hemolytic Disease of the Newborn • Hemolytic disease of the newborn is prevented with RhoGAM. • Prevents sensitization of mother’s immune system to Rh antigen.
Immune thrombocytopenic purpura also known as immune-mediated thrombocytopenia Similar situations can exist that lead to the destruction of red blood cells…this condition is most often referred to AIHA (autoimmune hemolytic anemia)
Type III Hypersensitivity(immune complex-mediated hypersensitivity) • A large quantity of soluble foreign Ag stimulates Ab that produce small, soluble Ag-Ab complexes • Immune complexes become trapped in tissues & incite a damaging inflammatory response • examples • Systemic lupus erythematosus (SLE) • Rheumatoid arthritis
Autoimmunity • In certain type II & III hypersensitivities, the immune system has lost tolerance to self molecules and forms autoantibodies and sensitized T cells against them. • More common in females • Disruption of function can be systemic or organ specific • Systemic lupus erythematosus • Rheumatoid arthritis • Endocrine autoimmunities • Myasthenia gravis • Multiple sclerosis
Type IV Hypersensitivity(delayed or cell-mediated hypersensitivity) • Cell-mediated • A delayed response to Ag involving activation of and damage by T cells • Delayed allergic response – skin response to allergens – tuberculin skin test, contact dermititis from plants, metals, cosmetics • Graft (transplant) rejection – reaction of cytotoxic T cells directed against foreign cells of a grafted tissue; involves recognition of foreign HLA/MHC
Graft rejection • Graft rejection is a normal immune response against foreign MHC proteins on the surface of the graft/transplant. • We try to match MHC proteins of donors and recipients as best as possible to prevent tissue rejection.
Immunodeficiency diseases • Components of the immune response system are absent. Deficiencies involve B and T cells, phagocytes, and complement • Primary immunodeficiency – genetically based congenital lack of B-cell and/or T cell activity • B cell defect – agammaglobulinemia – patient lacks antibodies • T cell defect – thymus is missing or abnormal • Severe combined immunodeficiency - both limbs of lymphocyte system are missing or defective; no adaptive immune response • Secondary (acquired) immune deficiency – due to damage after birth (infections, drugs, radiation) AIDS
Review of immunizations • Active vs. Passive (no memory cells with passive) • Artificially vs naturally acquired • Active artificial … you are vaccinated • Active natural … you had the infection/disease • Passive artificial … you received an injection of antibodies • Passive natural … mother’s milk