The remarkable magnitude of GALT as an inductive site for B-cells is documented by the fact that more than 80% of all Ig-producing blasts and plasma cells in an adult are located in the intestinal lamina propria (Brandtzaeg et al., 1999a). As mentioned above, most such terminally differentiated mucosal B-cells (immunocytes) produce J-chain-containing dimers and some larger polymers of IgA, collectively called pIgA. These polymers (as well as pentameric IgM with J chain) are efficiently transported externally as SIgA (and SIgM) antibodies by the pIgR (Norderhaug et al., 1999; Johansen et al., 2000), which is constituted by the membrane SC expressed basolaterally on the intestinal crypt cells and other secretory epithelia (Fig. 14.2).
The main purpose of the secretory antibody system is, in cooperation with innate mucosal defence mechanisms, to perform immune exclusion (Fig. 14.7). Most importantly, SIgA inhibits colonization and invasion of pathogens, and pIgR-transported pIgA and pentameric IgM antibodies may even inactivate viruses (e.g. rotavirus and influenza virus) inside secretory epithelial cells and carry the pathogens and their products back to the lumen (Fig. 14.7), thus avoiding cytolytic damage to the epithelium (Norderhaug et al., 1999). Both the agglutinating and the virus-neutralizing antibody effects of pIgA are superior to those of monomeric antibodies (Brandtzaeg et al., 1987), and SIgA antibodies may block microbial invasion quite efficiently. This has been particularly well documented in relation to the human immunodeficiency virus (Mazzoli et al., 1997), and specific SIgA antibodies isolated from human colostrum have been shown to be more efficient in this respect than comparable IgG antibodies (Hocini and Bomsel, 1999).
Induction of SIgA responses has likewise been shown to interfere significantly with mucosal uptake of soluble macromolecules in experimental animals
(Brandtzaeg et al., 1987). Collectively, therefore, the function of locally produced pIgA, including antibodies in breast milk, would be to inhibit or modulate the epithelial colonization of microorganisms and to dampen the penetration of soluble antigens; this effect is most probably enhanced by the relatively high levels of polyreactive SIgA antibodies (Quan et al., 1997). In the gut, interaction of SIgA with the endogenous protein Fv (Fv fragment binding protein) may, moreover, build an immune fortress by forming large complexes of intact or degraded antibodies with different specificities, thereby reinforcing immune exclusion (Bouvet and Fischetti, 1999). It has also been claimed that SIgA can enhance the sticking of certain bacteria to mucus, interfere with growth factors (e.g. iron) and enzymes necessary for pathogenic bacteria and parasites (Brandtzaeg et al., 1999a) and exert positive influences on the inductive phase of mucosal immunity, by promoting antigen uptake in GALT via putative IgA receptors on the M cells of FAE (Frey and Neutra, 1997). The latter possibility adds to the importance of breast-feeding in providing a supply of relevant SIgA antibodies for the infant's gut.
Interestingly, free SC released to the lumen (Fig. 14.2) may on its own be able to block epithelial adhesion of E. coli (Giugliano et al., 1995) and can bind the potent toxin of Clostridium difficile (Dallas and Rolfe, 1998). Also, a pneumococcal surface protein (SpsA) has been shown to interact with both free and bound SC (Hammerschmidt et al., 1997). Such observations suggest that SC has phylogenetically originated from the innate defence system before being exploited by the adaptive secretory immune system to function as pIgR.
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For many years, scientists have been playing out the ingredients that make breast milk the perfect food for babies. They've discovered to day over 200 close compounds to fight infection, help the immune system mature, aid in digestion, and support brain growth - nature made properties that science simply cannot copy. The important long term benefits of breast feeding include reduced risk of asthma, allergies, obesity, and some forms of childhood cancer. The more that scientists continue to learn, the better breast milk looks.