Immunoglobulin A IgA

Although IgA constitutes only 10%-15% of the total im-munoglobulin in serum, it is the predominant im-munoglobulin class in external secretions such as breast milk, saliva, tears, and mucus of the bronchial, genitourinary, and digestive tracts. In serum, IgA exists primarily as a monomer, but polymeric forms (dimers, trimers, and some tetramers) are sometimes seen, all containing a J-chain

Igd Hinge Region
(b) IgD
(c) IgE
Iga Immunoglobulins

Hinge region

J chain

J chain

Chain Immunoglobulin

Hinge region

Mucus Disulfide Bonds

called the J chain, that is linked by two disulfide bonds to the Fc region in two different monomers. Serum IgM is always a pentamer; most serum IgA exists as a monomer, although dimers, trimers, and even tetramers are sometimes present. Not shown in these figures are intrachain disulfide bonds and disulfide bonds linking light and heavy chains (see Figure 4-2).

FIGURE 4-13

General structures of the five major classes of secreted antibody. Light chains are shown in shades of pink, disulfide bonds are indicated by thick black lines. Note that the IgG, IgA, and IgD heavy chains (blue, orange, and green, respectively) contain four domains and a hinge region, whereas the IgM and IgE heavy chains (purple and yellow, respectively) contain five domains but no hinge region. The polymeric forms of IgM and IgA contain a polypeptide, called the J chain, that is linked by two disulfide bonds to the Fc region in two different monomers. Serum IgM is always a pentamer; most serum IgA exists as a monomer, although dimers, trimers, and even tetramers are sometimes present. Not shown in these figures are intrachain disulfide bonds and disulfide bonds linking light and heavy chains (see Figure 4-2).

polypeptide (see Figure 4-13d). The IgA of external secretions, called secretory IgA, consists of a dimer or tetramer, a J-chain polypeptide, and a polypeptide chain called secretory component (Figure 4-15a, page 93). As is explained below, secretory component is derived from the receptor that is responsible for transporting polymeric IgA across cell membranes. The J-chain polypeptide in IgA is identical to that found in pentameric IgM and serves a similar function in fa cilitating the polymerization of both serum IgA and secretory IgA. The secretory component is a 70,000-MW polypep-tide produced by epithelial cells of mucous membranes. It consists of five immunoglobulin-like domains that bind to the Fc region domains of the IgA dimer. This interaction is stabilized by a disulfide bond between the fifth domain of the secretory component and one of the chains of the dimeric IgA.

Iga Immunoglobulin

The daily production of secretory IgA is greater than that of any other immunoglobulin class. IgA-secreting plasma cells are concentrated along mucous membrane surfaces. Along the jejunum of the small intestine, for example, there are more than 2.5 X 1010 IgA-secreting plasma cells—a number that surpasses the total plasma cell population of the bone marrow, lymph, and spleen combined! Every day, a human secretes from 5 g to 15 g of secretory IgA into mucous secretions.

The plasma cells that produce IgA preferentially migrate (home) to subepithelial tissue, where the secreted IgA binds tightly to a receptor for polymeric immunoglobulin molecules (Figure 4-15b). This poly-Ig receptor is expressed on the basolateral surface of most mucosal epithelia (e.g., the lining of the digestive, respiratory, and genital tracts) and on glandular epithelia in the mammary, salivary, and lacrimal glands. After polymeric IgA binds to the poly-Ig receptor, the receptor-IgA complex is transported across the epithelial barrier to the lumen. Transport of the receptor-IgA complex involves receptor-mediated endocytosis into coated pits and directed transport of the vesicle across the epithelial cell to the luminal membrane, where the vesicle fuses with the plasma membrane. The poly-Ig receptor is then cleaved en-zymatically from the membrane and becomes the secretory component, which is bound to and released together with polymeric IgA into the mucous secretions. The secretory component masks sites susceptible to protease cleavage in the hinge region of secretory IgA, allowing the polymeric molecule to exist longer in the protease-rich mucosal environment than would be possible otherwise. Pentameric IgM is also transported into mucous secretions by this mechanism, although it accounts for a much lower percentage of antibody in the mucous secretions than does IgA. The poly-Ig receptor interacts with the J chain of both polymeric IgA and IgM antibodies.

Secretory IgA serves an important effector function at mucous membrane surfaces, which are the main entry sites for most pathogenic organisms. Because it is polymeric, secretory IgA can cross-link large antigens with multiple epi-topes. Binding of secretory IgA to bacterial and viral surface antigens prevents attachment of the pathogens to the mu-cosal cells, thus inhibiting viral infection and bacterial colonization. Complexes of secretory IgA and antigen are easily entrapped in mucus and then eliminated by the ciliated epithelial cells of the respiratory tract or by peristalsis of the gut. Secretory IgA has been shown to provide an important line of defense against bacteria such as Salmonella, Vibrio cholerae, and Neisseria gonorrhoeae and viruses such as polio, influenza, and reovirus.

Breast milk contains secretory IgA and many other molecules that help protect the newborn against infection during the first month of life (Table 4-3). Because the immune system of infants is not fully functional, breast-feeding plays an important role in maintaining the health of newborns.

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Responses

  • alaric
    What is polyig receptor on iga dimer called?
    8 years ago
  • Faizan Campbell
    What does heavy chain in immunoglobulin a do?
    8 years ago

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