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AUTOMMUNITY
This is the reaction of the immune system against the body’s own tissues. It results from the breakdown of self tolerance leading to recognition of self antigens as non-self. The body produces antibodies against its own antigens. Such antibodies are called autoantibodies that give rise to a lot of disorders in the body known as autoimmune diseases.
Mechanisms that lead to development of autoimmunity (Possible mechanisms that lead to breakdown of self tolerance)
a) Genetic predisposition
Individuals may inherit genes that predispose them to autoimmune diseases or they may lack genes that confer protection against autoimmune diseases
b) Hormonal factors
Autoimmune diseases occur mostly in women than in men. Although the exact role of sex hormones is not known, most autoimmune diseases are known to occur in women during their child bearing age when estrogen production is at its peak.
c) Infections
Infectious agents including bacteria and viruses have been proposed as possible stimulus for development of autoimmune diseases. These organisms cause inflammatory conditions that can lead to changes in self antigens provoking autoimmune responses.
d) Drugs
Drugs such as penicillin can trigger the production of autoantibodies. These drugs bind to erythrocytes leading to production of autoantibodies that may cause the destruction of red blood cells.
e) Release of sequestered antigens into circulation
These are antigens that are normally hidden away from the immune system and they may include myelin basic protein of the CNS, lens protein of the eye and spermatozoa antigens. Exposure of these antigens due to trauma of viral or bacterial infection may lead to autoimmunity.
f) Inappropriate expression of MHC molecules
The pancreatic β cells of individuals with diabetes express unusually high levels of MHC class II molecules. This inappropriate expression of MHC class II molecule may serve to sensitize self reactive T cells leading to autoimmunity.
g) Molecular mimicry
This is a mechanism of autoimmunity triggered by infection with a microbe containing antigens that cross react with self antigens. Immune responses to the microbe result in reactions against self tissues.
AUTOIMMUNE DISEASES
They are classified into two categories
Organ specific autoimmune diseases
Systemic/ Non-organ specific autoimmune diseases
ORGAN SPECIFIC AUTOIMMUNE DISEASES
The autoimmune responses are directed against antigens present only at particular organ. In some autoimmune diseases, autoantibodies bind to self antigens leading to their destruction while in other diseases autoantibodies bind to self antigens leading to either overstimulation of cells or suppression of normal functioning of the cell.
Such diseases include;-
Auto immune hemolytic anaemia
This involves autoantibodies to self red blood cells. The autoantibodies bind to antigens on the red blood cells leading to their lysis. Most drugs are not immunogenic by themselves but they act as haptens. The drugs form a complex with protein antigens on the red blood cells. The drug- RBC antigen complex induces the immune system to produce antibodies. These antibodies against the complex activate the complement resulting in RBC lysis.
Pernicious Anaemia
It’s a chronic disease resulting from non-absorption of vitamin B12 which is essential for development of RBCs. It is caused by autoantibodies to the membrane bound intrinsic factor found in the small intestines. The binding of autoantibodies to the membrane bound intrinsic factor blocks the absorption of vitamin B12. The number of functional mature RBCs decreases below normal, a conditional referred to as pernicious anaemia.
Myasthenia Gravis Disease
Autoantibodies are produce against acetylcholine receptors on muscle cells on the neuromuscular junction. This interferes with binding of acetylcholine and down modulates receptors leading to muscle weakness and paralysis.
Graves disease (hyperthyroidism)
It is caused by autoantibodies to thyroid stimulating hormone (TSH) receptors leading to overstimulation of receptors on thyroid gland. This results to excessive production of thyroid hormone, a condition known as hyperthyroidism.
Hashimoto’s Thyroiditis
It involves formation of autoantibodies against thyroid proteins, thyroglobulin and thyroperoxidase. These proteins are necessary for uptake of iodine by thyroid gland. The autoantibodies interfere with uptake of iodine.
Insulin dependent diabetes mellitus
Insulin is produced by β cells in the islets of langerhans cells in the pancreas. The insulin secreted by β cells is essential for glucose metabolism. Decreased production or non-production of insulin results in diabetes mellitus. Insulin dependent diabetes mellitus is a condition caused by autoantibodies against the β cells in the pancreas resulting in the destruction of β cells. Autoantibodies to β cells activate the complement system leading to destruction of the cells. Also, cytotoxic T cells produce cytokines which activate macrophages that destroy β cells.
Good pasture’s syndrome
It involves production of autoantibodies to certain antigens on kidney glomerulus and lung alveoli. The binding of autoantibodies to the membrane antigens in the lungs and kidney leads to complement activation resulting in inflammatory reactions resulting in nephritis and lung hemorrhage.
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