The mechanisms of self-tolerance protect one individual's body from the potentially self-reactive immune components. But these mechanisms sometime go wrong, resulting in an inappropriate response to the immune system against self-reactive immune components. This phenomenon is termed as autoimmunity. Autoimmunity was first described by Paul Ehlrich during the first of 20th century.
Self-reactive immunologic components are normally suppressed in normal individual by clonal anergy or clonal suppression. Irregularities in clonal anergy lead to the activation of self-reactive immune components. This self-reactive immune complexes generate humoral or cell mediated response against self-antigenic components. This in turn leads to autoimmune diseases.
When response is directed to a target antigen specific to a particular organ or gland, such that the results are strictly limited to that particular organ or gland it is called as organ specific auto-immune diseases. Organ-Specific Auto-immune diseases are of two types:
A. Diseases mediated by direct cellular damage
B. Diseases mediated by stimulating or blocking Auto-Antibodies
A. Diseases Mediated By Direct Cellular Damage
Direct cellular damages occur when self-reactive immune complexes like lymphocytes or antibodies bind to the cellular membrane of the affected organ or gland and causes cellular lysis or inflammation. The damaged cellular framework gets replaced by connective tissues and the function of the organ or gland declines. The several types of organ specific auto-immune diseases are as follows.
• Hashimoto's Thyroiditis
Hashimoto's thyroiditis is frequently found in middle-aged women. The patient with this auto-immune disease produces auto-antibodies and sensitized TDTH cells particular to the antigens produced from thyroid glands. The response is characterized by an immense infiltration of the thyroid gland by lymphocytes, macrophages and plasma cells. This inflammation of the thyroid gland causes goitre or a distinguishable enlargement of thyroid gland. Auto-antibodies are produced against the thyroid proteins, such as thyroglobulin and thyroid peroxidase. Interaction of auto-antibodies and these proteins impair the iodine intake mechanism of the thyroid gland and eventually lead to hypothyroidism.
• Goodpasture's Syndrome
In Goodpasture's syndrome auto-antibodies bind to the specific antigens in the basement membrane of kidney glomeruli and the alveoli of lungs. This leads to direct cellular damage and an inflammatory response generates. The symptoms of this disease are kidney damage and pulmonary haemorrhage which leads to death within some months of the onset of the disease.
• Insulin-Dependent Diabetes Melitus
Insulin dependent diabetes mellitus or IDDM affects 2.8% of the current world population as of 2000. IDDM results due to an auto-immune attack on the pancreas. The attack is directed against specialized insulin-producing cells called beta cells that are located in islet of Langerhans scattered throughout the pancreas. Auto-immune attack destroys beta cells resulting in a decrease in the production of insulin. The decrease in production of insulin results in an increase in the blood glucose levels. The destruction of beta cells in islet of Langerhans is due to auto antibodies against beta cells which include cytokines like IFN-ỵ, TNF-α and IL-1. The cell destruction is facilitated by antibody plus competent lysis or antibody dependent cell-mediated cytotoxicity (ADCC). The abnormalities in glucose metabolism results in serious metabolic problems like ketoacidosis and increased urine production. In later stage of the disease the blindness, renal failure, gangrene occurs.
• Autoimmune Anaemia's
Auto-immune anaemia's include Pernicious anaemia, auto-immune haemolytic anaemia and drug induced haemolytic anaemia. Interaction of auto-antibodies with RBC antigens induces anaemia. Complement mediated lysis or antibody mediated phagocytosis of RBC cells causes anaemia. This auto-immunologic expression decreases the absorption of vitamin B12 which hampers the production of RBC.
B. Diseases Mediated By Stimulating or Blocking Auto-Antibodies
In this type of auto-immune diseases antibodies acts as agonists or and binds to hormone receptors in place of the normal receptors and stimulate inappropriate antibody activity. In another type of these diseases the antibody blocks the receptor functionality. These types of auto-immune diseases are as follows.
• Graves 'Disease
In Graves' disease auto-antibodies act as an antagonists. Auto-antibodies mimic the action of TSH receptor in thyroid glands and binds to the TSH receptor. This binding of auto-antibodies with TSH receptor impairs the secretion of thyroid hormones. Irregularities in secretion of thyroid hormone affect the metabolism, growth and development of body.
• Myasthenia Gravis
Another auto-immune disease in this category is myasthenia gravis. In this disease auto-antibodies are produced to the acetylcholine receptors. This auto-antibody blocks the normal binding of acetylcholine and this induces degradation of the receptors. The outcome of the disease is degradation of the skeletal muscles. The first symptoms of the disease are drooping eyelids and inability to retract the sides of the mouth.
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