Autoimmune diseases involving direct cellular damage occur when lymphocytes or antibodies bind to cell-membrane antigens, causing cellular lysis and/or an inflammatory response in the affected organ. Gradually, the damaged cellular structure is replaced by connective tissue (scar tissue), and the function of the organ declines.
Brief description of a few examples of this type of autoimmune diseases :-
HASHIMOTO’s THYROIDITIS
In Hashimoto’s thyroiditis, which is most frequently seen in middle-aged women, an individual produces auto antibodies and sensitized TH1 cells specific for thyroid antigens. The DTH response is characterized by an intense infiltration of the thyroid gland by lymphocytes, macrophages, and plasma cells, which form lymphocytic follicles and germinal centers. The ensuing inflammatory response causes a goiter, or visible enlargement of the thyroid gland, a physiological response to hypothyroidism. Antibodies are formed to a number of thyroid proteins, including thyroglobulin and thyroid peroxidase, both of which are involved in the uptake of iodine. Binding of the auto-antibodies to these proteins interferes with iodine uptake and leads to decreased production of thyroid hormones (hypothyroidism).
AUTOIMMUNE ANEMIAS
Autoimmune anemias include pernicious anemia, autoimmune hemolytic anemia, and drug-induced hemolytic anemia. Pernicious anemia is caused by auto-antibodies to intrinsic factor, a membrane-bound intestinal protein on gastric parietal cells. Intrinsic factor facilitates uptake of vitamin B12 from the small intestine. Binding of the auto antibody to intrinsic factor blocks the intrinsic factor–mediated absorption of vitamin B12. In the absence of sufficient vitamin B12, which is necessary for proper hematopoiesis, the number of functional mature red blood cells decreases below normal. Pernicious anemia is treated with injections of vitamin B12, thus circumventing the defect in its absorption.
An individual with autoimmune hemolytic anemia makes auto-antibody to RBC antigens, triggering complement mediated lysis or antibody-mediated opsonization and phagocytosis of the red blood cells. One form of autoimmune anemia is drug-induced: when certain drugs such as penicillin or the anti-hypertensive agent methyldopa interact with red blood cells, the cells become antigenic. The immunodiagnostic test for autoimmune hemolytic anemias generally involves a Coombs test, in which the red cells are incubated with an anti–human IgG antiserum. If IgG auto antibodies are present on the red cells, the cells are agglutinated by the antiserum.
GOODPASTURE’s SYNDROME
In Goodpasture’s syndrome, auto-antibodies specific for certain basement-membrane antigens bind to the basement membranes of the kidney glomeruli and the alveoli of the lungs. Subsequent complement activation leads to direct cellular damage and an ensuing inflammatory response mediated by a buildup of complement split products. Damage to the glomerular and alveolar basement membranes leads to progressive kidney damage and pulmonary hemorrhage. Death may ensue within several months of the onset of symptoms. Biopsies from patients with Goodpasture’s syndrome stained with fluorescent-labeled anti-IgG and anti- C3b reveal linear deposits of IgG and C3b along the basement membranes.
Brief description of a few examples of this type of autoimmune diseases :-
HASHIMOTO’s THYROIDITIS
In Hashimoto’s thyroiditis, which is most frequently seen in middle-aged women, an individual produces auto antibodies and sensitized TH1 cells specific for thyroid antigens. The DTH response is characterized by an intense infiltration of the thyroid gland by lymphocytes, macrophages, and plasma cells, which form lymphocytic follicles and germinal centers. The ensuing inflammatory response causes a goiter, or visible enlargement of the thyroid gland, a physiological response to hypothyroidism. Antibodies are formed to a number of thyroid proteins, including thyroglobulin and thyroid peroxidase, both of which are involved in the uptake of iodine. Binding of the auto-antibodies to these proteins interferes with iodine uptake and leads to decreased production of thyroid hormones (hypothyroidism).
AUTOIMMUNE ANEMIAS
Pernicious Anemia
Autoimmune anemias include pernicious anemia, autoimmune hemolytic anemia, and drug-induced hemolytic anemia. Pernicious anemia is caused by auto-antibodies to intrinsic factor, a membrane-bound intestinal protein on gastric parietal cells. Intrinsic factor facilitates uptake of vitamin B12 from the small intestine. Binding of the auto antibody to intrinsic factor blocks the intrinsic factor–mediated absorption of vitamin B12. In the absence of sufficient vitamin B12, which is necessary for proper hematopoiesis, the number of functional mature red blood cells decreases below normal. Pernicious anemia is treated with injections of vitamin B12, thus circumventing the defect in its absorption.
Hemolytic Anemia
An individual with autoimmune hemolytic anemia makes auto-antibody to RBC antigens, triggering complement mediated lysis or antibody-mediated opsonization and phagocytosis of the red blood cells. One form of autoimmune anemia is drug-induced: when certain drugs such as penicillin or the anti-hypertensive agent methyldopa interact with red blood cells, the cells become antigenic. The immunodiagnostic test for autoimmune hemolytic anemias generally involves a Coombs test, in which the red cells are incubated with an anti–human IgG antiserum. If IgG auto antibodies are present on the red cells, the cells are agglutinated by the antiserum.
GOODPASTURE’s SYNDROME
In Goodpasture’s syndrome, auto-antibodies specific for certain basement-membrane antigens bind to the basement membranes of the kidney glomeruli and the alveoli of the lungs. Subsequent complement activation leads to direct cellular damage and an ensuing inflammatory response mediated by a buildup of complement split products. Damage to the glomerular and alveolar basement membranes leads to progressive kidney damage and pulmonary hemorrhage. Death may ensue within several months of the onset of symptoms. Biopsies from patients with Goodpasture’s syndrome stained with fluorescent-labeled anti-IgG and anti- C3b reveal linear deposits of IgG and C3b along the basement membranes.
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