Immunoglobulin A 490668 222842213 2008-07-01T11:21:39Z DOI bot 6652755 Citation maintenance. Formatted: title. You can [[WP:DOI|use this bot]] yourself! Please [[User:DOI_bot/bugs|report any bugs]]. [[Image:Immunglobulin_A_as_Dimer.png|thumb|The [[dimer]]ic IgA molecule. <br /> 1 [[H-chain]]<br /> 2 [[L-chain]]<br /> 3 [[J-chain]]<br /> 4 [[secretory component]]]] [[Image:Ig A.jpg|thumb|Ig A]] '''Immunoglobulin A''' ('''IgA''') is an [[antibody]] playing a critical role in mucosal immunity. More IgA is produced in mucosal linings than all other types of antibody combined.<ref>{{cite journal |author=S Fagarasan and T Honjo |title=Intestinal IgA Synthesis: Regulation of Front-line Body Defenses |journal=Nat. Rev. Immunology |volume=3 |pages=63–72 |year=2003 |pmid=12511876 |doi=10.1038/nri982}}</ref> However, sources are correct when they indicate [[immunoglobulin G]] as the most common form of immunoglobulin in the human body. In its secretory form, is the main [[immunoglobulin]] found in [[mucous membrane|mucous secretions]], including [[tears]], [[saliva]], [[colostrum]], [[intestinal juice]], [[vaginal fluid]] and secretions from the [[prostate]] and [[respiratory epithelium]]. It is also found in small amounts in blood. Because it is resistant to degradation by enzymes, secretory IgA can survive in harsh environments such as the digestive and respiratory tracts, to provide protection against [[microbe]]s that multiply in body secretions.<ref>{{cite book |last=Junqueira |first= Luiz C. |coauthors= Jose Carneiro |title= Basic Histology|year= 2003|publisher= McGraw-Hill|id= ISBN 0838505902}}</ref> IgA is a poor activator of the [[complement system]], and [[Opsonin|opsonise]]s only weakly. Its [[heavy chain]]s are of the type α. ==Forms== ===IgA1 vs. IgA2=== It exists in two [[Isotype (immunology)|isotypes]], IgA1 (90%) and IgA2 (10%): * IgA1 is found in serum and made by bone marrow B cells. * In IgA2, the heavy and light chains are not linked with [[disulfide]] but with [[noncovalent]] bonds. IgA2 is made by B cells located in the mucosae and has been found to secrete into [[colostrum]], maternal milk, [[tears]] and [[saliva]]. ===Serum vs. secretory IgA=== It is also possible to distinguish forms of IgA based upon their location - serum IgA vs. secretory IgA. IgA is found in secretions in a specific form called ''secretory IgA''', polymers of 2-4 IgA monomers linked by two additional chains. One of these is the [[J chain]] (joining chain), which is a [[polypeptide]] of molecular mass 15kD, rich with [[cysteine]] and structurally completely different from other immunoglobulin chains. This chain is formed in the IgA-secreting cells. The oligomeric forms of IgA in the external (mucosal) secretions also contain a polypeptide of a much larger molecular mass (70 kD) called the [[secretory component]] that is produced by [[epithelial cells]]. This molecule originates from the poly-Ig receptor (130 kD) that is responsible for the uptake and transcellular transport of oligomeric (but not monomeric) IgA across the epithelial cells and into secretions such as tears, saliva, sweat and gut fluid. ==IgA activity== The high prevalence of IgA in mucosal areas is a result of a cooperation between [[plasma cell]]s that produce polymeric IgA (pIgA), and mucosal epithelial cells that express an immunoglobulin receptor called the [[polymeric Ig receptor]] (pIgR). pIgA is released from the nearby activated plasma cells and binds to pIgR. This results in transportation of IgA across mucosal epithelial cells and its cleavage from pIgR for release into external secretions.<ref name=snoeck>{{cite journal |author=Snoeck V, Peters I, Cox E |title=The IgA system: a comparison of structure and function in different species |journal=Vet. Res. |volume=37 |issue=3 |pages=455–67 |year=2006 |pmid=16611558 |doi=10.1051/vetres:2006010}}</ref> In the blood, IgA interacts with an [[Fc receptor]] called FcαRI (or [[CD89]]), which is expressed on immune effector cells, to initiate inflammatory reactions.<ref name=snoeck/> Ligation of FcαRI by IgA containing immune complexes causes [[antibody-dependent cell-mediated cytotoxicity]] (ADCC), degranulation of [[eosinophil]]s and [[basophil]]s, [[phagocytosis]] by [[monocyte]]s, [[macrophage]]s, [[neutrophil]]s and [[eosinophil]]s, and triggering of respiratory burst activity by [[polymorphonuclear leukocyte]]s.<ref name=snoeck/> ==Transport== Polymeric IgA (mainly the secretory dimer) is produced by [[plasma cell]]s in the [[lamina propria]] adjacent to mucosal surfaces. It binds to the [[polymeric immunoglobulin receptor]] on the basolateral surface of epithelial cells and is taken up into the cell via [[endocytosis]]. The receptor-IgA complex passes through the cellular compartments before being secreted on the [[Lumen (anatomy)|luminal surface]] of the epithelial cells, still attached to the receptor. [[Proteolysis]] of the receptor occurs and the dimeric IgA molecule, along with a portion of the receptor known as the [[secretory component]], are free to diffuse throughout the lumen.<ref>{{cite journal |author=CS Kaetzel, JK Robinson, KR Chintalacharuvu, JP Vaerman, and ME Lamm |title=The polymeric immunoglobulin receptor (secretory component) mediates transport of immune complexes across epithelial cells: a local defense function for IgA |journal=Proc Natl Acad Sci USA |volume=88 |issue=19 |pages=8796–8800 |year=1991 |pmid=1924341 |doi=10.1073/pnas.88.19.8796}}</ref> In the gut, it can bind to the mucus layer on top of the epithelial cells to form a barrier capable of neutralizing threats before they reach the cells. ==Pathology== Decreased or absent IgA, termed [[selective IgA deficiency]], can be a clinically significant [[immunodeficiency]]. ''Neisseria gonorrhœae'' (causes [[Gonorrhea|gonorrhea]]) releases a protease which destroys IgA. [[IgA nephropathy]] is caused by IgA deposits in the kidneys. It is not yet known why IgA deposits occur in this chronic disease. Some theories suggest it is an abnormality of immune system that results in these deposits. ==See also== * [[TGF beta]] * [[Antibodies]] * [[IgM]], [[IgD]], [[IgE]], [[IgG]] ==References== <references/> ==External links== * {{MeshName|Immunoglobulin+A}} {{immune_system}} {{Immune_proteins}} [[Category:Antibodies]] [[Category:Glycoproteins]] [[Category:Immune system]] [[ar:غلوبيولين مناعي A]] [[da:Immunoglobulin A]] [[de:Immunglobulin A]] [[es:Inmunoglobulina A]] [[fr:Superfamille des immunoglobulines]] [[it:IgA]] [[ja:免疫グロブリンA]] [[pl:Immunoglobuliny A]] [[pt:Imunoglobulina A]] [[fi:IgA]]