Immunoglobulin A is an antibody that plays a critical role in mucosal immunity.
More IgA is produced in mucosal linings than all other types of antibody combined; between
three and five grams are secreted into the intestinal lumen each day.
This accumulates up to 15% of the total immunoglobulin produced in the entire body.
IgA has two subclasses and can exist in a dimeric form called secretory IgA.
In its secretory form, IgA is the main immunoglobulin found in mucous secretions, including tears,
saliva, sweat, colostrum and secretions from the genitourinary tract, gastrointestinal
tract, prostate and respiratory epithelium.
It is also found in small amounts in blood.
The secretory component of sIgA protects the immunoglobulin from being degraded by proteolytic
enzymes, thus sIgA can survive in the harsh gastrointestinal tract environment and provide
protection against microbes that multiply in body secretions.
sIgA can also inhibit inflammatory effects of other immunoglobulins.
IgA is a poor activator of the complement system, and opsonises only weakly.
Its heavy chains are of the type α.
Forms IgA1 vs. IgA2
IgA exists in two isotypes, IgA1 and IgA2.
While IgA1 predominates in serum, IgA2 percentages are higher in secretions than in serum; the
ratio of IgA1 and IgA2 secreting cells varies in the different lymphoid tissues of the human
body: IgA1 is the predominant IgA subclass found
in serum.
Most lymphoid tissues have a predominance of IgA-producing cells.
In IgA2, the heavy and light chains are not linked with disulfide, but with noncovalent
bonds.
In secretory lymphoid tissues, the share of IgA2 production is larger than in the non-secretory
lymphoid organs.
Both IgA1 and IgA2 have been found in external secretions like colostrum, maternal milk,
tears and saliva, where IgA2 is more prominent than in the blood.
Polysaccharide antigens tend to induce more IgA2 than protein antigens.
Serum vs. secretory IgA It is also possible to distinguish forms of
IgA based upon their location - serum IgA vs. secretory IgA.
In secretory IgA, the form found in secretions, polymers of 2-4 IgA monomers are linked by
two additional chains; as such, the molecular weight of slgA is 385,000D. One of these is
the J 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 secretions also contain a polypeptide of a
much larger molecular mass called the secretory component that is produced by epithelial cells.
This molecule originates from the poly-Ig receptor that is responsible for the uptake
and transcellular transport of oligomeric 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 cells that produce polymeric IgA, and mucosal
epithelial cells that express an immunoglobulin receptor called the polymeric Ig receptor.
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.
In the blood, IgA interacts with an Fc receptor called FcαRI, which is expressed on immune
effector cells, to initiate inflammatory reactions.
Ligation of FcαRI by IgA containing immune complexes causes antibody-dependent cell-mediated
cytotoxicity, degranulation of eosinophils and basophils, phagocytosis by monocytes,
macrophages, and neutrophils, and triggering of respiratory burst activity by polymorphonuclear
leukocytes.
SIgA primarily acts by blockading epithelial receptors, by sterically hindering attachment
to epithelial cells, and by immune exclusion.
Since sIgA is a poor opsonin and activator of complement, simply binding a pathogen isn't
necessarily enough to contain it—specific epitopes may have to be bound to sterically
hinder access to the epithelium.
Immune exclusion is a process of agglutinating polyvalent antigens or pathogens by crosslinking
them with antibody, trapping them in the mucus layer, and/or clearing them peristaltically.
The oligosaccharide chains of sIgA’s secretory component can associate with the mucus layer
that sits atop epithelial cells.
Production of sIgA against specific antigens depends on sampling of M cells and underlying
dendritic cells, T cell activation, and B cell class switching in GALT, mesenteric lymph
nodes, and isolated lymphoid follicles in the small intestine.
Transport Polymeric IgA is produced by plasma cells
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 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.
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 cell.
Pathology Decreased or absent IgA, termed selective
IgA deficiency, can be a clinically significant immunodeficiency.
Neisseria gonorrhœae, Streptococcus pneumoniae, and Haemophilus influenzae type B all release
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 an abnormality of the immune system results in these deposits.
Celiac disease involves IgA pathology due to the presence of IgA antiendomysial antibodies.
Henoch–Schönlein purpura is a systemic disorder caused by deposits of IgA and compliment
component 3 in the small vessels.
HSP occurs usually in small children and involves the skin and connective tissues, scrotum,
joints, gastrointestinal tract and kidneys.
It usually follows an upper respiratory infection and resolves within a couple weeks as the
liver clears out the IgA aggregates.
See also List of target antigens in pemphigus
TGF beta References
External links Immunoglobulin A at the US National Library
of Medicine Medical Subject Headings