Organ specific autoimmune

what is organ specific autoimmune diseases and it examples.

1. Organ-specific autoimmune diseases SUBMITTED BY, SRUTHI JOSY 19PZOO9683

2. Classification of autoimmune disorders Autoimmune diseases can be broadly divided into systemic and organ-specific or localised autoimmune disorders, depending on whether they affect a single organ or multiple systems in the body. An  organ-specific disease is one in which an immune response is directed toward antigens in a single organ. Examples are  Addison disease , in which autoantibodies attack the adrenal cortex, and  myasthenia gravis , in which they attack neuromuscular cells. In  systemic diseases  the immune system attacks self antigens in several organs.  Systemic lupus erythematosus , for example, is characterized by  inflammation  of the skin, joints, and kidneys, among other organs.

3. Organ specific or localized autoimmune disease In an organ-specific autoimmune disease, the immune response is usually directed to a target antigen unique to a single organ or gland, so that the manifestations are largely limited to that organ. The cells of the target organs may be damaged directly by humoral or cell mediated effector mechanisms. Alternatively, anti-self antibodies may overstimulate or block the normal function of the target organ.

4. Hashimoto’s Thyroiditis In Hashimoto’s thyroiditis , an individual produces autoantibodies and sensitized T H 1 cells specific for thyroid antigens. Th is disease is much more common in women, often striking in middle-age. 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, leading to decreased thyroid function and hypothyroidism (decreased production of thyroid hormones). The resulting delayed-type hypersensitivity (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.

5. Type 1 Diabetes Mellitus Type 1 diabetes mellitus (T1DM) or insulin-dependent diabetes, seen mostly in youth under the age of 14 and is less common than Type 2, or non- insulin dépendent diabetes mellitus . T1DM is caused by an autoimmune attack against insulin-producing cells (beta cells) scattered throughout the pancreas, which results in decreased production of insulin and consequently increased levels of blood glucose. The attack begins with cytotoxic T lymphocyte (CTL) infiltration and activation of macrophages, frequently referred to as insulitis, followed by cytokine release and the production of autoantibodies, which leads to a cell-mediated DTH response. The subsequent beta-cell destruction is thought to be mediated by cytokines released during the DTH response and by lytic enzymes released from the activated macrophages. Autoantibodies specific for beta cells may contribute to cell destruction by facilitating either antibody-mediated complement lysis or antibody-dependent cell-mediated cytotoxicity (ADCC).

6. Th e abnormalities in glucose metabolism associated with T1DM result in serious metabolic problems that include ketoacidosis (accumulation of ketone, a breakdown product from fat) and increased urine production. The late stages of the disease are oft en characterized by atherosclerotic vascular lesions (which cause gangrene of the extremities due to impeded vascular flow), renal failure, and blindness. If untreated, death can result. Th e most common therapy for T1DM is daily administration of insulin. Although this is helpful, sporadic doses are not the same as metabolically regulated, continuous, and controlled release of the hormone. Unfortunately, diabetes can remain undetected for many years, allowing irreparable loss of pancreatic tissue to occur before treatment begins.

7. Photomicrographs of an islet of Langerhans in (a) pancreas from a normal mouse and ( b) Pancreas from a mouse with a disease resembling insulin dependent diabetes mellitus (b) (a)

8. Myasthenia Gravis Myasthenia gravis is the classic example of an autoimmune disease mediated by blocking antibodies. A patient with this disease produces auto-antibodies that bind the acetylcholine receptors (AchRs) on the motor end plates of muscles, blocking the normal binding of acetylcholine and inducing complement-mediated lysis of the cells. The result is a progressive weakening of the skeletal muscles. Ultimately, the antibodies cause the destruction of the cells bearing the receptors. Th e early signs of this disease include drooping eyelids and inability to retract the corners of the mouth. Without treatment, progressive weakening of the muscles can lead to severe impairment of eating as well as problems with movement. However, with appropriate treatment, this disease can be managed quite well and afflicted individuals can lead a normal life. Treatments are aimed at increasing acetylcholine levels (e.g., using cholinesterase inhibitors), decreasing antibody production (using corticosteroids or other immunosuppressants ), and/or removing antibodies (using plasmapheresis).

9. Myasthenia gravis and impaired muscle contraction. (a) Normal release of the neurotransmitter acetylcholine stimulates muscle contraction. (b) In myasthenia gravis, autoantibodies block the receptors for acetylcholine ( AChr ) on muscle cells, resulting in paralysis.

10. Graves Disease Graves’ disease is an example where binding of autoantibodies to cell surface receptors results in activation of the cell. In Graves’ disease, autoantibodies to thyroid stimulating hormone (TSH) receptors bind to TSH receptors on thyroid and lead to excessive production of thyroid hormones. This may cause conflicting symptoms because it may stimulate the thyroid to make too much thyroid hormone or block  thyroid  hormone production entirely, making diagnosis more difficult. Signs and symptoms of Graves disease include heat intolerance, rapid and irregular heartbeat, weight loss,  goiter  (a swollen thyroid gland, protruding under the skin of the throat and  exophthalmia  (bulging eyes) often referred to as Graves  ophthalmopathy .

11. Exophthalmia, or Graves ophthalmopathy, is a sign of Graves disease Goiter, a hypertrophy of the thyroid, is a symptom of Graves disease and Hashimoto thyroiditis .

12. Addison Disease Destruction of the  adrenal glands  (the glands lying above the kidneys that produce glucocorticoids , mineralocorticoids , and sex steroids) is the cause of  Addison disease , also called  primary adrenal insufficiency (PAI) . Today, up to 80% of Addison disease cases are diagnosed as autoimmune Addison disease (AAD), which is caused by an autoimmune response to adrenal tissues disrupting adrenal function. Disruption of adrenal function causes impaired metabolic processes that require normal steroid hormone levels, causing signs and symptoms throughout the body. There is evidence that both humoral and CD4 T H 1-driven CD8 T-cell–mediated immune mechanisms are directed at the adrenal cortex in AAD. There is also evidence that the autoimmune response is associated with autoimmune destruction of other endocrine glands as well, such as the  pancreas  and  thyroid , conditions collectively referred to as  autoimmune polyendocrine syndromes (APS) .

13. In up to 80% of patients with AAD, antibodies are produced to three enzymes involved in steroid synthesis: 21-hydroxylase (21-OH), 17α-hydroxylase, and cholesterol side-chain–cleaving enzyme.  The most common autoantibody found in AAD is to 21-OH, and antibodies to any of the key enzymes for steroid production are diagnostic for AAD. The adrenal cortex cells are targeted, destroyed, and replaced with fibrous tissue by immune-mediated inflammation. In some patients, at least 90% of the adrenal cortex is destroyed before symptoms become diagnostic. Symptoms of AAD include weakness, nausea, decreased appetite, weight loss,  hyperpigmentation ,  hyperkalemia  (elevated blood potassium levels),  hyponatremia  (decreased blood sodium levels),  hypoglycemia  (decreased levels of blood sugar),  hypotension  (decreased blood pressure),  anemia ,  lymphocytosis  (decreased levels of white blood cells), and fatigue. Under extreme stress, such as surgery, accidental trauma, or infection, patients with AAD may experience an adrenal crisis that causes the patient to vomit, experience abdominal pain, back or leg cramps, and even severe hypotension leading to shock.

14. Hyperpigmentation is a sign of Addison disease.

15. Autoimmune Hemolytic Anemia In autoimmune hemolytic anemia, auto antibodies to self- RBCs are formed. The autoantibodies bind to antigens on RBCs and lead to the lysis of RBCs. Most drugs are not immunogenic by themselves, but they may act as haptens . The drug forms a complex with protein antigens on RBCs. The drug-RBC antigen complex induces the immune system to produce antibodies. The antibodies formed against the drug-RBC antigen complex bind to the RBC and activate the complement cascade, resulting in RBC lysis.

16. Pernicious Anemia Pernicious anemia is a chronic disease resulting from the non-absorption of vitamin B 12 , which is essential for the development of RBCs. Pernicious anemia, is most common in late adult life. The basic abnormality of the disease is severe atrophic gastritis, wherein there is extreme deficiency of all the gastric secretions, including intrinsic factor. The gastric lesion probably develops due to an autoimmune attack on gastric cells.

17. The autoantibodies to intrinsic factor may interfere with the absorption of vitamin B 12  by the following mechanisms: i . In pernicious anemia, the intrinsic factor autoantibodies in gastric juice may bind to intrinsic factor and block the binding of vitamin B 12  to intrinsic factor ii. The autoantibody to intrinsic factor may bind to intrinsic factor-B 12  complex and interferes with the absorption of the complex. Consequently, the absorption of vitamin B 12  is interfered, resulting in decreased production of RBCs. Pernicious anemia patients are treated by regular vitamin B 12  injections.

18. Goodpasture’s Syndrome Autoantibodies to certain antigens on the membrane of kidney glomeruli and lung alveoli are formed in a condition called Good pasture’s syndrome. Binding of autoantibodies to the membrane antigens in lung and kidney leads to complement activation, resulting in inflammatory reactions in lung and kidney. Consequently , the kidneys are damaged and the patient also suffers from pulmonary hemorrhage (i.e. bleeding from lungs).

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