![](/olcweb/styles/shared/spacer.gif) | ![](/sites/dl/free/0072320427/title/cover_image.JPG) Foundations in Microbiology, 4/e Kathleen Park Talaro,
Pasadena City College Arthur Talaro
Disorders in Immunity
Chapter CapsuleI. Immunopathology:
The study of disease states involving the malfunction of the immune system is called immunopathology.
A. Allergy, or hypersensitivity, is an exaggerated, adverse expression of certain immune responses. B. Abnormal responses to foreign antigens are characteristic of immune complex disease; undesirable reactions to foreign tissues are graft rejections. C. Autoimmunity involves abnormal responses to self antigens. A deficiency or loss in immune function is called immunodeficiency. II. Allergy/Hypersensitivity
A. An allergic reaction is a heightened immune response to antigens involving misdirected but natural mechanisms of humoral immunity, cellular immunity, and inflammation. B. The four types of immune reactions are classified according to the type of lymphocyte involved, type of antigen, and nature of damage. III. Type I Hypersensitivities
A. Immediate-onset allergies involve contact with allergens, antigens that affect certain people; susceptibility is inherited; allergens enter through four portals: Inhalants are breathed in (pollen, dust); ingestants are swallowed (food, drugs); injectants are inoculated (drugs, bee stings); contactants react on skin surface (cosmetics, glue).B. Mechanism: On first contact with allergen, specific B cells react with allergen and form a special antibody class called IgE, which affixes by its Fc receptor to mast cells and basophils.
1. This sensitizing dose primes the allergic response system. 2. Upon subsequent exposure with a provocative dose, the same allergen binds to the IgE-mast cell complex.3. This causes degranulation, release of intracellular granules containing mediators (histamine, serotonin, leukotriene, prostaglandin), with physiological effects such as vasodilation and bronchoconstriction.4. Symptoms are rash, itching, redness, increased mucous discharge, pain, swelling, and difficulty in breathing. C. Specific Diseases
1. An atopic allergy is a local reaction to an allergen. 2. Allergic rhinitis (hay fever) is a seasonal respiratory allergy.3. Asthma is a chronic respiratory condition.4. Atopic dermatitis (eczema) is characterized by an itchy
skin rash. 5. Food allergy involves respiratory, cutaneous, and skin reactions to common foodstuffs. D. Systemic anaphylaxis is an acute, extreme reaction to allergens that results in severe respiratory and circulatory symptoms. Death may occur through compromised respiration and circulatory collapse.E. Diagnosis of allergy can be made by a histamine release test on basophils; serological assays for IgE; and skin testing, which injects allergen into the skin and mirrors the degree of reaction.F. Control of allergy involves drugs to interfere with the action of histamine, inflammation, and release of cytokines from mast cells. Desensitization therapy involves the administration of purified allergens. IV. Type II Hypersensitivities
A. Type II reactions involve the interaction of antibodies, foreign cells, and complement, leading to lysis of the foreign cells. In transfusion reactions, humans may become sensitized to special antigens on the surface of the red blood cells of other humans. B. The ABO blood groups are genetically controlled: Type A blood has A antigens on the RBCs; type B has B antigens; type AB has both A and B antigens; and type O has neither antigen. People produce antibodies against A or B antigens if they lack these antigens. Antibodies can react with antigens if the wrong blood type is transfused.C. Rh factor is another RBC antigen that becomes a problem if an Rh– mother is sensitized by an Rh1 fetus. A second fetus can receive antibodies she has made against the factor and develop hemolytic disease of the newborn. Prevention involves therapy with Rh immune globulin. V. Type III Immune Complex Reactions
A. Exposure to a large quantity of soluble foreign antigens (serum, drugs) stimulates antibodies that produce small, soluble Ag-Ab complexes.
1. These immune complexes are trapped in various organs and tissues, which incites a damaging inflammatory response. 2. Arthus reaction is a local reaction to a series of injected antigens in the same body site; it may lead to tissue destruction. 3. Serum sickness is a systemic disease resulting from repeated injections of foreign proteins; high levels of circulating immune complexes are deposited in various organs and cause tissue damage. VI. Autoimmunity
A. In certain type II and III hypersensitivities, the immune system has lost tolerance to self molecules (autoantigens) and forms autoantibodies and sensitized T cells against them. Disruption of function can be systemic or organ specific.B. Autoimmune diseases are genetically determined and more common in females.
1. Systemic lupus erythematosus (SLE) is a chronic, systemic disease in which antibodies are deposited in the kidney, skin, lungs, and heart. 2. Rheumatoid arthritis is a chronic systemic autoimmunity in the joints; appears to be associated with immune complexes that cause chronic inflammation and scar tissue.3. Endocrine autoimmunities include Grave disease, Hashimoto thyroiditis, and types I and II diabetes mellitus.4. Myasthenia gravis is an immune attack upon the myoneural junction, with muscle paralysis.5. In multiple sclerosis, T cells and antibodies damage the myelin sheath of nerve cells; accompanied by motor and sensory loss. VII. Type IV Cell-Mediated Hypersensitivity:
A delayed response to antigen involving the activation of and damage by T cells.
A. Delayed allergic response: Skin response to allergens, including infectious agents. Example is tuberculin reaction; contact dermatitis is caused by exposure to plants (ivy, oak) and simple environmental molecules (metals, cosmetics); cytotoxic T cells acting on allergen elicit a skin reaction.B. Graft rejection: Reaction of cytotoxic T cells directed against foreign cells of a grafted tissue; involves recognition of foreign HLA by T cells and rejection of tissue.
1. Host may reject graft; graft may reject host.2. Types of grafts include: autograft, from one part of body to another; isograft, grafting between identical twins; allograft, between two members of same species; xenograft, between two different species.3. All major organs may be successfully transplanted.4. Allografts require tissue match (HLA antigens must correspond); rejection is controlled with drugs. VIII. Immunodeficiency Diseases
Components of the immune response system are absent. Deficiencies involve B and T cells, phagocytes, and complement.
A. Primary immunodeficiency is genetically based, congenital; defect in inheritance leads to lack of B-cell activity, T-cell activity, or both. B. B-cell defect is called agammaglobulinemia; patient lacks antibodies; serious recurrent bacterial infections result. In Ig deficiency, one of the classes of antibodies is missing or deficient.C. In T-cell defects, the thymus is missing or abnormal. In DiGeorge syndrome, the thymus fails to develop; afflicted children experience recurrent infections with eucaryotic pathogens and viruses; immune response is generally underdeveloped.D. In severe combined immunodeficiency (SCID), both limbs of the lymphocyte system are missing or defective; no adaptive immune response exists; fatal without replacement of bone marrow or other therapies.E. Secondary (acquired) immunodeficiency is due to damage after birth (infections, drugs, radiation). AIDS is the most common of these; T helper cells are main target; deficiency manifests in numerous opportunistic infections and cancers. IX. Cancer and the Immune System
A. Cancer is characterized by overgrowth of abnormal tissue, also known as a neoplasm. It appears to arise from malfunction of immune surveillance.
1. Tumors can be benign (a nonspreading local mass of tissue) or malignant (a cancer) that spreads (metastasizes) from the tissue of origin to other particular sites by means of the circulation.2. Malignant tumors may be carcinomas, originating from epithelial tissue, or sarcomas, originating from embryonic connective tissue. 3. Cancers occur in nearly every cell type (except mature, nondividing cells). B. Cancer cells appear to share a common basic mechanism involving some type of gene alteration that turns a normal gene (proto-oncogene) into an oncogene.
1. The oncogene transforms the cell and triggers uncontrolled growth and abnormal structure and function.2. Gene alterations may be due to chromosome disruptions, viral infection, or the actions of chemical and physical carcinogens.3. Malignant cancer cells display special markers, respond to growth factors, and lose their cohesiveness.4. Treatment is with surgery, chemicals, radiation, and immunotherapy.
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