Critical role of breastfeeding

When much of the transferred maternal IgG has been catabolized around 2 months of age, the infant becomes still more dependent on antibodies from breast milk for specific humoral immunity. At least 90% of the pathogens attacking humans use the mucosae as portals of entry; mucosal infections are in fact a major killer of children below the age of 5 years, being responsible for more than 14 million deaths of children annually in developing countries. Diarrhoeal disease alone claims a toll of 5 million children per year, or about 500 deaths every hour. These sad figures document the need for mucosal vaccines against common infectious agents, in addition to the importance of advocating breast-feeding. Convincing epidemiological documentation suggests that the risk of dying from diarrhoea is reduced 14-24 times in nursed children (Hanson et al., 1993; Anon., 1994). Indeed, exclusively breast-fed infants are better protected against a variety of infections (Pisacane et al., 1994; Wold and Hanson, 1994; Newman, 1995; Wright et al., 1998) and apparently also against allergy, asthma (Saarinen and Kajosaari, 1995; Oddy et al., 1999; Kull et al., 2001) and coeliac disease (Brandtzaeg, 1997a). Interestingly, experiments in neonatal rabbits strongly suggest that SIgA is a crucial anti-microbial component of breast milk (Dickinson et al., 1998). The role of secretory antibodies for mucosal homoeostasis is furthermore supported by the fact that knockout mice lacking SIgA and SIgM show increased mucosal leakiness (Johansen et al., 1999).

After the peak of passive immunity mediated by maternal IgG and antibodies from breast milk, the survival of the infant will, to an increasing extent, depend on its own adaptive immune responses. At mucosal surfaces, such responses are largely expressed by local antibody production (Brandtzaeg et al., 1999a). The cellular basis for this first-line humoral defence is the fact that exocrine glands and secretory mucosae contain most of the body's activated B-

cells, terminally differentiated to Ig-producing blasts and plasma cells (collectively called immunocytes). These cells produce mainly dimers and some larger polymers of IgA (collectively called pIgA), which, along with pentameric IgM, can be actively transported through the serous type of secretory epithelia (Brandtzaeg, 1973, 1974a, b, 1975; Brandtzaeg et al., 1968), including lactat-ing mammary glands (Brandtzaeg, 1983), to act in a first-line mucosal defence (Fig. 14.2). As discussed later, this function depends on the epithelial polymeric Ig receptor (pIgR), which consists of a transmembrane glycoprotein, also known as membrane secretory component (SC).

Immune Componeent Breastfeeding
  1. 14.2. Model for local generation of secretory immunoglobulin (Ig)A and secretory IgM. J-chain-containing dimeric IgA (IgA + J) and pentameric IgM (IgM + J) are produced by local plasma cells (left). Polymeric Ig receptor (pIgR) or membrane secretory component (SC) is synthesized by secretory epithelial cell in the rough endoplasmic reticulum (ER) and matures in the Golgi complex by terminal glycosylation (•-). In the trans-Golgi network (TGN), pIgR is sorted for delivery to the basolateral plasma membrane. The receptor becomes phosphorylated (O-) on a serine residue in its cytoplasmic tail. After endocytosis, ligand-complexed and unoccupied pIgR is delivered to basolateral endosomes and sorted for transcytosis to apical endosomes. Some recycling from basolateral endosomes to the basolateral surface may occur for unoccupied pIgR (not shown). Receptor recycling also takes place at the apical cell surface as indicated, although most pIgR is cleaved to allow extrusion of SIgA, SIgM and free SC to the lumen. During epithelial translocation, covalent stabilization of SIgA regularly occurs (disulphide bond between bound SC and one IgA subunit indicated), whereas free SC in secretions stabilizes the non-covalently bound SC in SIgM (dynamic equilibrium indicated). (Modified from Brandtzaeg et al., 1999a.)
  2. 14.2. Model for local generation of secretory immunoglobulin (Ig)A and secretory IgM. J-chain-containing dimeric IgA (IgA + J) and pentameric IgM (IgM + J) are produced by local plasma cells (left). Polymeric Ig receptor (pIgR) or membrane secretory component (SC) is synthesized by secretory epithelial cell in the rough endoplasmic reticulum (ER) and matures in the Golgi complex by terminal glycosylation (•-). In the trans-Golgi network (TGN), pIgR is sorted for delivery to the basolateral plasma membrane. The receptor becomes phosphorylated (O-) on a serine residue in its cytoplasmic tail. After endocytosis, ligand-complexed and unoccupied pIgR is delivered to basolateral endosomes and sorted for transcytosis to apical endosomes. Some recycling from basolateral endosomes to the basolateral surface may occur for unoccupied pIgR (not shown). Receptor recycling also takes place at the apical cell surface as indicated, although most pIgR is cleaved to allow extrusion of SIgA, SIgM and free SC to the lumen. During epithelial translocation, covalent stabilization of SIgA regularly occurs (disulphide bond between bound SC and one IgA subunit indicated), whereas free SC in secretions stabilizes the non-covalently bound SC in SIgM (dynamic equilibrium indicated). (Modified from Brandtzaeg et al., 1999a.)

IgA-producing immunocytes are normally undetectable in human intestinal mucosa before 10 days of age but thereafter a rapid increase takes place, although IgM immunocytes usually remain predominant up to 1 month (Brandtzaeg et al., 1991; Brandtzaeg, 1996b, 1998). Adult salivary IgA levels are reached quite late in childhood, but only a small increase of IgA-producing cells has been reported to take place in the intestinal mucosa after 1 year. These observations have been made in industrialized countries; a faster development of the IgA immune system is usually seen in children from developing countries, reflecting the adaptability of mucosal immunity according to the environmental antigenic load, as discussed below. This should not detract from the fact that breast-feeding is highly desirable for both its immunological and its nutritional value (B0rresen, 1995).

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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