Organspecific Autoimmune Disorders

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A. Blood disorders

1. Anemia, leukopenia, and thrombocytopenia. Autoantibodies that react with red blood cells (RBCs), white blood cells (WBCs), and platelets result in anemia, leukopenia, and thrombocytopenia, respectively.

2. Multiple myeloma, the malignant transformation of a single plasma cell clone, results in an excess of IgG or another immunoglobulin class (paraproteins). Patients may secrete Bence Jones proteins (monoclonal light chains) in their urine.

B. Central nervous system (CNS) disorders

1.. Allergic encephalomyelitis is a demyelinating disease that can occur after infection or immunization.

a. The condition can be mimicked experimentally by immunizing animals with homologous extracts of brain or a nonapeptide from the basic protein of myelin.

b. The experimental disease can be transferred to normal animals with lymphocytes sensitized to the nonapeptide, implicating CMI in the demyelination process.

2. Multiple sclerosis is a chronic, relapsing disease of unknown etiology that is characterized immunologically by mononuclear cell infiltrates and demyelinating lesions (plaques) in the white matter of the CNS.

a. Clinical features. Patients usually have increased levels of IgG in the cerebrospinal fluid. Elevated titers to measles and other viruses appear in the cerebrospinal fluid, suggesting a viral etiology.

b. Immunologic features. Patients with MS generally exhibit a decrease in suppressor T-cell function, which indicates an immunoregulatory disorder.

3. Myasthenia gravis results from a defect in neuromuscular transmission.

a. Clinical features include muscle weakness and fatigue. Patients often exhibit thymic hyperplasia or a thymoma.

b. Immunologic features

(1) Myasthenia gravis is associated with the presence of an anti-acetylcholine receptor antibody. Binding of this antibody with the receptor at the postsynaptic membrane of the neuromuscular junction results in the loss (endocy-tosis) of the receptor.

(2) An inability to transmit the acetylcholine-induced signal to muscle fibers causes the clinical signs.

C. Endocrine disorders

1. Chronic thyroiditis (Hashimoto's disease, hypothyroidism) is a self-limiting disease with a probable genetic basis that affects mainly women.

a. Chronic thyroiditis is characterized by autoantibodies and CMI to thyroglobu-lin or thyroid peroxidase. This reactivity causes progressive destruction of the thyroid gland.

b. Antibody-dependent cell-mediated cytotoxicity (ADCC) may be responsible for the tissue damage.

2. Graves' disease (hyperthyroidism) is characterized by T cell and B cell infiltration of the thyroid gland, leading to the formation of autoantibodies to the thyroid-stimulating hormone (TSH) receptor. The autoantibodies may compete with TSH, bind to the TSH receptor site, and induce uncontrolled TSH-like activity. Clinical features include a diffuse goiter and thyrotoxicosis.

3. Diabetes mellitus (insulin-dependent diabetes, juvenile onset, type I diabetes) is characterized by the destruction of insulin-producing cells in the pancreas. Either humoral or cell-mediated anti-islet cell activity can be operative. There is no evidence of an autoimmune pathogenesis for non—insulin-dependent (maturity onset, type II) diabetes.

D. Gastrointestinal tract disorders

1. Pernicious anemia is caused by impaired gastrointestinal absorption of vitamin B12, resulting in weakness and chronic fatigue.

a. Immunologic features

(1) Pernicious anemia occurs secondary to T cell damage to the gastric parietal cell. The gastric parietal cell normally synthesizes intrinsic factor, the agent responsible for the transport of vitamin B12 into the blood.

(2) Anti-parietal cell and anti-intrinsic factor antibodies are found in most patients. The latter block the transport function of intrinsic factor, and contribute to the disease process.

b. Treatment. Injection of vitamin B12 bypasses the need for gastric absorption and corrects the deficiency.

2. Ulcerative colitis is characterized by chronic inflammatory lesions that are confined to the rectum and colon. These lesions are accompanied by the infiltration of monocytes, lymphocytes, and plasma cells.

a. Patients' lymphocytes exert cytotoxicity against colonic epithelial cells in culture.

b. Patients may also have antibodies that are cross-reactive with Escherichia coli, but the disease is of unknown etiology.

3. Crohn's diseaseis an inflammatory, granulomatous disease that involves T and B cells, macrophages, and neutrophils. The disease usually occurs in the submucosal area of the terminal ileum. This chronic progressive disease is often suspected but has not been established as being of microbial etiology.

4. Chronic active hepatitis is characterized by an infiltration of the liver by T cells, B cells, and monocytes. The condition may result from faulty immunoregulation because of decreased suppressor cell numbers.

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