Breast Milk: Proactive Immunomodulation and Mucosal Protection Against Viruses and Other Pathogens

Chiara Cerini; Grace M Aldrovandi

Disclosures

Future Virology. 2013;8(11):1127-1134. 

In This Article

Breast Milk Antibodies

Breast milk is a remarkably 'altruistic' secretion; that is, its contents are directed at protecting the infant with minimal or no benefit to the mother. Not only is the concentration of secretory antibodies (mainly IgA) in breast milk remarkably high (10–100-fold higher than in serum),[13] milk antibodies also possess a broad range of specificities, reflecting both maternal immunologic memory and antibodies directed towards pathogens that do not infect breast tissues, such as rotavirus.[14] Secretory antibodies in milk mirror maternal antigenic stimulation of mucosa-associated lymphoid tissue (MALT) both in the gut and the airways. Given the symbiosis between the breastfed infant and his/her mother during the first weeks of life, the microorganisms in the mother's environment are likely the same as those encountered by the infant. Intriguingly, milk composition changes (i.e., increase in the total number of white blood cells and higher TNF-α levels) have been documented in relation to active infection in the nursing infant.[15]

Mothers may thus be considered as immune 'factories', providing infants with antibodies that prevent, postpone or attenuate diseases caused by pathogens in their environment. In contrast to most therapeutics and immunizations, breast milk displays the unique potential to adapt itself to the requirements of the infant. Timely immune defenses are tapped from its constituents by immune regulation, modulation and immune acceleration to stimulate novel substances; these ad hoc modifications provide defense even in the face of evolving organisms.[15]

Antibodies in milk are either transferred from plasma by transudation or locally produced by cells that migrate to the mammary gland from other mucosal sites.[16]

During the latter stages of pregnancy, hormones, chemotactic factors and cellular addressins induce T and B cells homing from inductive sites (the gut and bronchial-associated tissues) to the lactating breast.[17,18] Although all classes of immunoglobulins can be detected in milk, over 90% are IgA; IgM and IgG are less abundant.[19] By using sensitive measuring techniques, IgD and IgE can also be detected.[20] Human colostrum contains more than 1 g/l IgA, and during the first year of lactation, concentrations are maintained at approximately 0.5 g/day.[21] By contrast, less than 20% of maternal serum immunoglobulin is IgA; most are IgG.[22]

IgA in milk is principally in the form of secretory IgA (sIgA), which serves as a first line of mucosal defense. Maternal supply of sIgA is important as infant intestinal IgA production does not begin until several months of age, and even at 1 year of age serum IgA levels are only 20% of adult levels.[22] Although the extent to which antibodies are absorbed in early life remains controversial, it is most likely modest, except perhaps in preterm infants.[23–25] Unlike other antibody isotypes, secretory IgA is resistant to degradation in the protease-rich external environments of mucosal surfaces, and the majority of ingested sIgA survives passage through the intestinal tract intact for at least the first year of life, providing mucosal protection in spite of the increasing surface area of the GI tract.[26,27]

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