18.6 Autoimmune Diseases
Table 18.4 Characteristics of Some Autoimmune Diseases
Disease (Known MHC Relationship)
Major Mechanism of Tissue Damage
Graves' disease (DR3)
Autoantibodies bind thyroid-stimulating hormone receptor, causing overstimulation of thyroid
Myasthenia gravis (DR3)
Autoantibodies bind to acetylcholine receptor on muscle, preventing muscle contraction
Insulin-dependent diabetes mellitus (DR3/DR4)
T-cell destruction of pancreatic cells
Autoimmune hemolytic anemia
Red blood cells
Antibody, complement, and phagocyte destruction of red cells
Rheumatoid arthritis (DR4)
Widespread, especially joints
Lymphocyte destruction of joint tissues; immune complexes of IgG and anti-IgG
Systemic lupus erythematosus (DR3)
Widespread (glomerulonephritis, vasculitis, arthritis)
Autoantibodies to DNA and other nuclear components form immune complexes in small blood vessels
babies also experience muscle weakness, since IgG antibodies cross the placenta. Fortunately, the effect is not permanent, as these IgG antibodies decay within a few months and the babies are no longer affected. Treatment of myasthenia gravis includes the administration of drugs that inhibit the enzyme cholinesterase, allowing acetylcholine to accumulate so some contact with receptors can occur. Immunosuppressive medications and thymectomy are helpful in many cases. The role of the thymus in this disease is not understood.
Insulin-dependent diabetes mellitus is a common autoimmune disease caused by cellular mechanisms. In this form of diabetes there is a lack of insulin, resulting in an increase of sugar in the blood. This leads to marked thirst and increase in urine production. The peak onset of this disease is about 12 years of age; thus, it is also called juvenile-onset diabetes. In the United States more than 100,000 children with this disease require daily insulin injections. After many years of diabetes, blindness, kidney failure, or other severe or fatal complications often occur. In insulin-dependent diabetes mellitus, although autoantibodies are present, the major damage is destruction of the insulin-producing cells of the pancreas by infiltrating cyto-toxic T cells.
A combination of antibody and cellular mechanisms is active in some autoimmune diseases, such as rheumatoid arthritis (figure 18.9). This crippling inflammatory condition is one of the most common autoimmune diseases, occurring in both sexes and in adults and children all over the world. About 1% of males and 3% of females in the United States are affected. Rheumatoid arthritis is most common in women aged 30 to 50. There is an infiltration of Th1 cells, the inflammatory CD4 T cells, into the joints. When stimulated by specific antigens there, the T cells release cytokines that cause inflammation. Autoantibodies are also formed and contribute to widespread tissue damage by forming immune complexes.
Autoimmune diseases are usually treated with immunosuppres-sants that kill dividing cells and thus control the response, or drugs that interfere with T-cell signaling, such as cyclosporin. Also, steroids and other anti-inflammatory drugs are often used. Replacement therapy is necessary in some autoimmune diseases; for example, insulin in diabetes or thyroid hormone in some of the autoimmune thyroid diseases.
In insulin-dependent diabetes mellitus, attempts are being made to cure the disease by replacing the tissues destroyed by immune cells. Transplantation of the pancreas or insulin-producing cells of the pancreas offers hope for a cure. In fact, many people have had successful pancreas transplants, but the method is not widely used because dangerous immunosup-pressive agents must be given to prevent rejection. Generally,
454 Chapter 18 Immunologic Disorders only people with advanced diabetes who require a kidney transplant, and must have the immunosuppressive drugs anyway, are given pancreas transplants. Research efforts are directed toward developing better methods of transplantation, such as enclosing the pancreatic cells within semipermeable membranes to protect them from attack by immune cells.
Ideally, it would be better to induce tolerance to the specific antigen causing the autoimmune response. Interesting experimental approaches are being tested in some autoimmune diseases. In a mouse model of diabetes, mice fed with insulin were protected from diabetes. Rheumatoid arthritis patients often have an active immune response to collagen, a protein prominent in the joints and surrounding tissues. An experimental treatment involves feeding solutions of animal collagen daily to the patients. This experimental approach should not be confused with the popular fad of taking pills containing collagen to treat the degenerative osteoarthritis of aging, which results from the wearing-down of cartilage and other collagen-containing compounds. The pills are taken with the hope of rebuilding cartilage and repairing the damage caused by aging. Osteoarthritis is not an immunologically mediated disease. The rationale of the experiments in the immunologically mediated rheumatoid arthritis depends on a well-known phenomenon called feeding or oral tolerance. Antigen introduced by the oral route can cause a local intestinal immune response with release of cytokines, down-regulation of antigen receptors, and deletion of immune cells. Clinical trials of oral administration of antigen have shown benefit in several autoimmune diseases. However there is much to be learned about the immunological mechanisms, antigen preparations, dose and duration of treatment. ■ immunological tolerance, p. 394
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