C O N T E N T SDescriptionSee also: Antibody, immunoglobulins
IgA represents about 15% to 20% of immunoglobulins in the blood, although it is primarily secreted across the mucosal tract into the stomach and intestines. It is also found in maternal milk, tears and saliva. This immunoglobulin helps to fight against pathogens that contact the body surface, are ingested, or are inhaled. It does not activate complement, and opsonises only weakly. Its heavy chains are of the type α. It exists in two forms, IgA1 (90%) and IgA2 (10%) that differ in the structure. IgA1 is composed like other proteins, however in IgA2 the heavy and light chains are not linked with disulfide but with noncovalent bonds. Though IgA2 is less in serum, it accounts for major secretory antibody. The IgA found in secretions have a special form. They are dimeric molecules, linked by two additional chains. One of these is the J chain (from join), which is a polypeptide of molecular mass 1,5 kD, rich with cysteine and structurally completely different from other immunoglobulin chains. This chain is formed in the antibodies secreting cells. The dimeric form of IgA in the outer secretions has also a polypeptide of the same molecular mass (1,5 kD) that is called the secretory chain and is produced by the epithelial cells. It is also possible to find trimeric and even tetrameric IgA.
Decreased or absent IgA, termed selective IgA deficiency, can be a clinically significant immunodeficiency. Secretory IGA is typically depressed in non-secretors. DiscussionThe role of IgA is closely related to the potential for gut related health problems. Ig-A is most commonly used by the body to "soak up" allergic substances from the digestive tract. It is usually evenly distributed throughout the gut tissue except in specialized lymphoid areas where large amounts are manufactured and encapsulated. Lymphoid tissue is found in those areas where immune activity is constantly required, such as the appendix, tonsils and Peyer's Patches of the intestines, areas which routinely become inflamed. IgA has two major functions. The first is to cause bacteria and allergic substances to stick to the mucus membranes. The second is to turn on the alternative complement pathway to destroy them. Improper function or secretion of IgA has been implicated in a variety of immune complex disorders including systemic lupus erythematosis and phlebitis. IgA is often found with gut mucus, usually with one end of the immunoglobulin tailored to adhere to and anchor with the mucus lining and the other, "business end" of the molecule projecting out into the gut ready for immune reactions if necessary. Calculations suggest that up to 50g of IgA may be synthesized by the gut daily, a mass equivalent to the immunoglobulin producing tissue of the spleen. Most B lymphocytes at the external mucosa are dedicated to IgA synthesis and form a recirculating pool of cells that home preferentially back to mucosal sites. Antigens present in the small intestine are sampled by a special type of cell, called an [M cell]?, located over each Peyer's patch and bordering on the intestinal lumen. The antigens are transferred to an environment of immune cells, accessory antigen presenting cells, and regulatory T cells within the patch. After antigen stimulation, precursors of IgA plasma cells migrate via the lymphatics to the blood, the spleen and the liver; then they return to the gut or localize at distant mucosal sites. Several factors have been postulated to explain the accumulation of potential IgA producing cells at these specialized sites. The mucosal environment, rich in microbial antigens and mitogens is known to influence the immune specificity of lymphocytes in mucosal tissue. T cells have been described that act on surface IgA positive B cells to increase or suppress IgA synthesis. When foreign material attempts to pass through the gut wall, IgA binds to it and forms an immune complex. Immune complexes are destroyed right at the site of attachment to IgA in the gut wall or transported to the liver and cleared by [Kuppfer cells]?. Insufficient IgA production is a common immunodeficiency (it is genetically produced in 1 of 600 individuals of European origin, and can result from dietary imbalance, tonsillectomy or appendectomy). If there is insufficient IgA in the tissues to bind with microbes or allergic particles, they will pass into the portal circulation and liver. If the liver is incapable of dealing with the immune complexes coming from intestinal absorption, they will pass into the systemic circulation and stimulate a general immune response. Allergic disorders and auto immunity occur with undue frequency in the milder forms of IgA deficiency. The former comprises reaginic IgE type) allergy in general and food sensitivity, especially gluten-sensitive malabsorption, in particular. The frequency of auto antibodies in IgA deficiency remains a riddle. Perhaps they appear as a result of excessive absorption of foreign material cross-reacting with self-substances, e.g. reticulin?; alternatively they may be the hallmarks of slow virus infections made possible by the failure of the gut barrier. IgA class antibodies are not found in very high concentrations in the blood. Rather, it is found very commonly on the mucosal surfaces of the body. Typically IgA is bound to the mucus at one end, with the free, or business end, sticking freely out.IgA is found abundantly in saliva, tears and breast milk (especially colostrum) and is the primary defense at mucosal surfaces such as bronchioles of the lungs, the nasal passages, prostate, vagina, and intestine. It normally guards against bacterial and viral infections. IgA deficiency is the most commonly seen immune deficiency. The deficiency is lifelong and precautions need to be taken to prevent infections. In general, IgA Deficiency occurs once in every 400 to 2,000 individuals. However, its incidence varies across racial and ethnic lines. Many IgA-deficient patients are healthy, with no more than the usual number of infections. Others may typically suffer with recurrent ear, sinus, or lung infections that may not respond to standard courses of antibiotics. These patients can have an increased frequency of allergies, asthma, chronic diarrhea (often due to parasite), and autoimmune diseases. IgA and secretor statusIn tests on 202 Caucasians, IgA levels were found to be significantly lower in non-secretors than in secretors. This probably helps to explain why non-secretors have higher incidences of rheumatic heart disease and chronic kidney disease (glomerulonephritis) over non-secretors: The lower levels of IgA cannot prevent microorganisms from gaining access to the blood stream from the oral cavity and digestive tract. IgA and antibodies to dietary lectinsIn a study looking at subjects with kidney problems (nephropathy) resulting from autoimmune disease and deposition of immune complexes in the kidney’s filtration system, anywhere from 19% to 38% (depending on the nationality of the subjects studied) had antibodies against common dietary lectins, which was significant in that none of the healthy controls had any such antibodies.
ABO blood groups and secretory IgA variance in breast milkArch Dis Child Fetal Neonatal Ed 1994 Nov;71(3):F192-F197 IgA antibodies in human milk: epidemiological markers of previous infections?Nathavitharana KA, Catty D, McNeish AS Institute of Child Health, University of Birmingham.
Dietary antigens and primary immunoglobulin A nephropathyJ Am Soc Nephrol 1992 Apr;2(10 Suppl):S173-S180 Coppo R, Amore A, Roccatello D Nephrology and Dialysis Department, Regina Margherita Children's Hospital, Turin, Italy.
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