In healthy individuals the immune system constantly protects us from the native and foreign microorganisms – such as viruses, bacteria, and parasites – that might make us ill. However in some individuals this protection can be inappropriately misdirected against our own tissues and cells, giving rise to autoimmunity. Diseases that result from this phenomenon are known as autoimmune diseases.
Under normal circumstances specialized systems regulate the immune system to ensure host tissue is not attacked. A failure of immune regulation in autoimmunity means that antibodies (autoantibodies) and auto reactive immune cells attack the body’s own tissues leading to autoimmune disease.
Autoimmune disorders are a broad spectrum of disease that can affect any part of the body. More than 80 have been identified, a considerable number with similar symptoms. Inflammation is the classic sign of autoimmunity although how this impacts on an individual is determined by which part of the body is affected.
Autoimmune disorders can be placed into two general types: those that are localized to specific organs or tissues (such as thyroiditis) or those that are systemic and damage many organs or tissues (such as systemic lupus erythematosus).
Determinants of Autoimmune Disease
Although ADs in humans are genetically complex, significant advances in understanding have occurred over the past several years. For many ADs, the break in peripheral self-tolerance leading to an anti-self-immune response is linked to an encounter with a particular pathogen, chemical, drug, toxin, or hormone.
However, the single most important factor contributing to AD is the genetic make-up of the host. A complex constellation of AD susceptibility alleles and haplotypes exists that determines the ongoing deregulation of self-tolerance mechanisms.
An individual may have more than one autoimmune disease
Interestingly, there are remarkable overlaps at each end of the spectrum. Thyroid antibodies occur with a high frequency in pernicious anaemia patients who have gastric autoimmunity, and these patients have a higher incidence of thyroid autoimmune disease than the normal population.
Similarly, patients with thyroid autoimmunity have a high incidence of stomach autoantibodies and, to a lesser extent, the clinical disease itself, namely pernicious anaemia.
The mechanisms of immunopathological damage vary depending on where the disease lies in the spectrum. Where the antigen is localized in a particular organ, Type II hypersensitivity and cell-mediated reactions are most important.
In non-organ-specific autoimmunity, immune complex deposition leads to inflammation through a variety of mechanisms, including complement activation and phagocyte recruitment.
Examples of localized autoimmune diseases
• Addison’s disease – this disease results from damage to the outer layer of the adrenal gland (the adrenal cortex), of which autoimmunity is the most common cause. As a result of this damage the adrenal gland does not produce enough steroid hormones (primary adrenal insufficiency), resulting in symptoms which include fatigue, muscle weakness, and a loss of appetite. This can be fatal if not recognized and treated, but treatment is relatively simple.
• Grave’s disease – affecting the thyroid, Grave’s disease is one of the most common causes of hyperthyroidism. It results from the production of antibodies that mimic Thyroid Stimulating Hormone, which produces a false signal causing the thyroid gland to produce excessive thyroid hormone. Symptoms including insomnia, tremor, and hyperactivity.
• Type 1 diabetes – diabetes mellitus type 1 is a consequence of the autoimmune destruction of cells in the pancreas which produce insulin. Insulin is essential to control blood sugar levels and if left uncontrolled the disease can lead to serious complications, such as damage to the nerves, heart disease, and problems with the retina. Without adequate treatment type 1 diabetes would be fatal.
• Crohn’s disease – a type of inflammatory bowel disease (IBD), Crohn’s is a result of chronic inflammation of the lining of the gastrointestinal tract that can cause diarrhoea, abdominal pain, and fatigue.
Examples of systemic autoimmune diseases
• Rheumatoid arthritis – a chronic condition that causes painful stiffness and swelling in the joints. Rheumatoid arthritis is a result of the immune system attacking tissues in the joint lining, eventually leading to damage of the joint itself. Rheumatoid arthritis can also effect inflammation around other organs, such as the heart and lungs. It differs from osteoarthritis, which is generally caused by mechanical stresses on the joint.
• Multiple sclerosis – a chronic condition that can cause significant disability, multiple sclerosis is a disease in which the electrically insulating layers of the nerves are destroyed, thus affecting signalling between the brain and other parts of the body.
• Lupus – systemic lupus erythematosus is a complex condition affecting many parts of the body, including the skin, joints, heart, lungs and nervous system. It occurs as a result of a widespread systemic autoimmune reaction and results in symptoms including fatigue, joint pain, and rashes.
• Scleroderma – in scleroderma the immune system attacks the connective tissue under the skin, resulting in a thickening of these tissues. In more severe forms it can affect blood circulation and internal organs.