Fig. 10.28 Dimeric IgA is the major class of antibody present in the lumen of the gut. IgA is synthesized by plasma cells in the lamina propria and transported into the lumen of the gut through epithelial cells at the base of the crypts. Dimeric IgA binds to the layer of mucus overlying the gut epithelium and acts as an antigen-specific barrier to pathogens and toxins in the gut lumen The structure of a molecule of FcRn (blue) is shown bound to one chain of the Fc portion of IgG (red), at the interface of the Cγ2 and Cγ3 domains, with the Cγ2 region at the top. The β2-microglobulin component of the FcRn is green. The dark-blue structure attached to the Fc portion of IgG is a carbohydrate chain, reflecting glycosylation. FcRn transports IgG molecules across the placenta in humans and also across the gut in rats and mice. It also has a role in maintaining the levels of IgG in adults. Although only one molecule of FcRn is shown binding to the Fc portion, it is thought that it takes two molecules of FcRn to capture one molecule of IgG. Courtesy of
Fig. 10.29 The neonatal Fc receptor (FcRn) binds to the Fc portion of IgG.
P. Björkman.
10-17 The neonatal Fc receptor carries IgG across the placenta and prevents IgG excretion from the body.
Newborn infants are especially vulnerable to infection, having had no previous exposure to the microbes in the environment they enter at birth. IgA antibodies are secreted in breast milk and are transferred to the gut of the newborn infant, where they provide protection from newly encountered bacteria until the infant can synthesize its own protective antibody. IgA is not the only protective antibody that a mother passes on to her baby. Maternal IgG is transported across the placenta directly into the bloodstream of the fetus during intrauterine life; human babies at birth have as high levels of plasma IgG as their mothers, and with the same range of antigen specificities. The selective transport of IgG from mother to fetus is due to an IgG transport protein in the placenta, FcRn (neonatal Fc receptor), which is closely related in structure to MHC class I molecules. Despite this similarity, FcRn binds IgG quite differently from the binding of peptide to MHC class I molecules, because its peptide-binding groove is occluded. It binds to the Fc portion of IgG molecules (Fig. 10.29). Two molecules of FcRn bind one molecule of IgG, bearing it across the placenta. Maternal IgG is ingested by the newborn animal from its mother’s milk and colostrum, the protein-rich fluid secreted by the early postnatal mammary gland. In this case, FcRn transports the IgG from the lumen of the neonatal gut into the blood and tissues. Interestingly, FcRn is also found in adults in the gut and liver and on endothelial cells. Its function in adults is to maintain the levels of IgG in plasma, which it does by binding antibody, endocytosing it, and recycling it to the blood, thus preventing its excretion from the body.
By means of these specialized transport systems, mammals are supplied from birth with antibodies against pathogens common in their environments. As they mature and make their own antibodies of all isotypes, these are distributed selectively to different sites in the body (Fig. 10.30). Thus, throughout life, class switching and the distribution of antibody classes throughout the body provide effective protection against infection in extracellular spaces.
10-18 High-affinity IgG and IgA antibodies can neutralize toxins and block the infectivity of viruses and bacteria.