The effector mechanisms of humoral immunity described so far may be active at any site in the body to which anti bodies gain access. As mentioned previously, antibodies are produced in peripheral lymphoid organs and bone marrow and readily enter the blood, from which they may go anywhere. Antibodies also serve vital protective functions at two special anatomic sites: the mucosal organs and the fetus.

Mucosal Immunity

 Immunoglobulin A (IgA) is produced in mucosal lymphoid tissues, transported across epithelia, and binds to and neutralizes microbes in the lumens of the mucosal organs (Fig. 1). Microbes often are inhaled or ingested, and antibodies that are secreted into the lumens of the respiratory or gastrointestinal tract bind to these microbes and prevent them from colonizing the host. This type of immunity is called mucosal immunity (or secretory immunity). The principal class of antibody produced in mucosal tissues is IgA. In fact, IgA accounts for about two-thirds of the approximately 3 g of antibody produced daily by a healthy adult, reflecting the vast surface area of the intestines. The propensity of B cells in mucosal epithelial tissues to produce IgA is because the cytokines that induce switching to this isotype, including transforming growth factor β (TGF-β), are produced at high levels in mucosa-associated lymphoid tissues. In addition, IgA-producing B cells that are generated in regional lymph nodes or spleen tend to home to mucosal tissues in response to chemokines produced in these tissues. Also, some of the IgA is produced by a subset of B cells, called B-1 cells, best studied in rodents, which also have a propensity to migrate to mucosal tissues; these cells secrete IgA in response to nonprotein antigens, without T cell help.

Fig1. Transport of immunoglobulin A (IgA) through epithelium. In the mucosa of the gastrointestinal and respiratory tracts, IgA is produced by plasma cells in the lamina propria and is actively transported through epithelial cells by an IgA-specific Fc receptor, called the poly-Ig receptor because it recognizes IgM as well. On the luminal surface, the IgA with a portion of the bound receptor is released. Here the antibody recognizes ingested or inhaled microbes and blocks their entry through the epithelium.

Intestinal mucosal B cells are located in the lamina propria, beneath the epithelial barrier, and IgA is produced in this region. To bind and neutralize microbial pathogens in the lumen before they invade, the IgA must be transported across the epithelial barrier into the lumen. Transport through the epithelium is carried out by a special Fc receptor, the poly-Ig receptor, which is expressed on the basal surface of the epithelial cells. This receptor binds IgA, endocytoses it into vesicles, and transports it to the luminal surface. Here the receptor is cleaved by a protease, and the IgA is released into the lumen still carrying a portion of the bound poly-Ig receptor (the secretory component). The attached secretory component protects the antibody from degradation by proteases in the gut. The antibody can then recognize microbes in the lumen and block their binding to and entry through the epithelium. IgA-mediated mucosal immunity is the mechanism of protection from poliovirus infection that is induced by oral immunization with the attenuated virus.

The gut contains a large number of commensal bacteria that are essential for basic functions such as absorption of food and, therefore, have to be tolerated by the immune system. IgA antibodies are produced mainly against potentially harmful and proinflammatory bacteria, thus blocking their entry through the gut epithelium.. 

Neonatal Immunity

Maternal antibodies are transported across the placenta to the fetus and across the gut epithelium of neonates, protecting the newborn from infections. Newborn mammals have incompletely developed immune systems and are unable to mount effective immune responses against many microbes. During their early life, they are protected from infections by antibodies acquired from their mothers. This is an example of naturally occurring passive immunity. Neonates acquire maternal antibodies by two routes. During pregnancy, maternal IgG binds to the FcRn expressed in the placenta, and is transported into the fetal circulation. After birth, infants ingest maternal IgA antibodies that are secreted into their mothers’ colostrum and milk. Ingested IgA antibodies provide mucosal immune protection to the neonate. Thus, neonates acquire the antibody profiles of their mothers and are protected from infectious microbes to which the mothers were exposed or vaccinated.

مواضيع ذات صلة

Immunologic Tolerance: General Principles and Significance

Adaptive Immunity

Innate Immunity

The Complement System

Opsonization and Phagocytosis

Neutralization of Microbes and Microbial Toxins

IMMUNOGLOBULIN VARIANTS

Typical Immunoglobulin Molecule

أنماط تفاعلات فرط الحساسية

دور جهاز المناعة في الحساسية الدوائية

Properties of Antibodies That Determine Effector Function

Generation of Plasma Cells and Memory B Cells