Striking species differences

The enterocytes of mammals play a vital role in defence of the neonate, not only by forming a mechanical barrier but also by transferring breast-milk-derived maternal antibodies from the gut lumen, thus providing passive systemic immunity in the newborn period. This enterocytic Ig transmission differs remarkably among species. In the ungulate (horse, cattle, sheep, pig), the whole length of the intestine is involved in a non-selective protein uptake, including all Ig isotypes, in a poorly defined pinocytic process. Because colostrum of these animals is particularly rich in IgG, this antibody class will preferentially reach the circulation of the neonate via its gut epithelium during the two first postnatal days, after which so-called 'gut closure' takes place (Mackenzie, 1990). Rodents, on the other hand, express an Fc receptor specific for IgG apically on neonatal enterocytes in the proximal small intestine. This receptor (FcRn), which disappears at weaning, has been particularly well characterized on enterocytes of the neonatal rat; it is a major histocompatibility complex (MHC) class I-related molecule, associated with ^-microglobulin (Simister and Mostov, 1989). Complexes of FcRn and IgG are internalized in clathrin-coated pits at the base of the microvilli; binding of the ligand takes place in the acidic luminal environment, and IgG release occurs at physiological pH on the basolateral face of the enterocyte, after which the receptor is recycled.

In contrast to the animal species mentioned above, the human fetus acquires maternal IgG via the placenta (Mackenzie, 1990) and perhaps, to some extent, from swallowed amniotic fluid via FcRn expressed by fetal enterocytes (Israel et al., 1993). Indeed, a bidirectional transport mechanism for IgG was recently demonstrated in a human intestinal epithelial cell line (Dickinson et al., 1999), but the functional significance of FcRn on enterocytes in the human newborn remains unknown. Intestinal uptake of secretory IgA (SIgA) antibodies after breast-feeding appears of little or no importance in the support of systemic immunity (Ogra et al., 1977; Klemola et al., 1986), except perhaps in the preterm infant (Weaver et al., 1991). Although gut closure in humans normally seems to occur mainly before birth, a patent mucosal barrier function may not be established until after 2 years of age; the different variables involved in this process are poorly defined (van Elburg et al., 1992). Interestingly, the post-natal colonization of commensal bacteria is important both to establish (Hooper et al., 2001) and to regulate (Neish et al., 2000) an appropriate epithelial barrier.

Immediately after birth, the mucosae are bombarded by a large variety of microorganisms, as well as by protein antigens from the environment, the latter particularly in formula-fed infants. The mucosal surface to be protected is enormous, probably more than 100 times that of the skin. In fact, the various mucosae are favoured as portals of entry by the majority of infectious agents, allergens and carcinogens. In most mucosal tissues, the epithelial barrier is monolayered and therefore quite vulnerable, so the defence of this large surface area is a formidable task. Nevertheless, most babies growing up under privileged conditions show remarkably good resistance to infections if their innate non-specific mucosal defence mechanisms are normally developed. This can be explained by the fact that immune protection of their mucosae is additionally provided by maternal IgG antibodies, which are distributed in interstitial tissue fluid at a concentration 50-60% of the intravascular level. In the first postnatal period, only occasional traces of SIgA and SIgM normally occur in the intestinal juice, whereas some IgG is more often present. This might be a result of external FcRn-mediated transmission or, perhaps more probably, it reflects passive epithelial 'leakage' from the highly vascularized lamina propria, which, particularly after 34 weeks of gestation, contains readily detectable maternal IgG (Brandtzaeg et al., 1991). However, an optimal mucosal barrier function in the neonatal period unquestionably depends on an adequate supply of breast milk, as highlighted in relation to mucosal infections, especially in developing countries (Anon., 1994). In the Westernized part of the world, the anti-infectious protective value of breast-feeding is clinically most apparent in preterm infants (Hylander et al., 1998).

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New Mothers Guide to Breast Feeding

New Mothers Guide to Breast Feeding

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.

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