Evolution of Immunologic Functions of the Mammary Gland and the Postnatal Development of Immunity
GOLDMAN, ARMOND S.; CHHEDA, SADHANA; GAROFALO, ROBERTO
Departments of Pediatrics [A.S.G., S.C., R.G.], Microbiology and Immunology [A.S.G.], Pathology [A.S.G.], and Human Biological Chemistry and Genetics [A.S.G.], The University of TexasMedical Branch, Galveston, Texas 77555-0369
Received June 3, 1997; accepted October 23, 1997.
Correspondence and reprint requests: Armond S. Goldman, M.D., Division of Immunology/Allergy, Department of Pediatrics, Children's Hospital, Room 2.360, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0369.
Physiologic delays in production ofimmune factors occur in mammals including Homo sapiens. This finding is counter to a basic tenet of biologic evolution, because such delays increase the risk of infections. The disadvantage is, however, offset by defense factors in milk of the species in whom the developmental delay occurs. Reciprocal relationships between the production of immune factors by the lactating mammary gland and theproduction of those defense agents during early infancy are found in all investigated mammalian species. Thus, the evolution of these processes is closely related. Certain immunologic components of milk are highly conserved, whereas others vary according to the species. The variations most likely evolved by genetic mutations and natural selection. In addition, the immune composition of mammalian milksis associated with developmental delays in the same immunologic agents. Furthermore, most closely related mammals, such as humans and chimpanzees, are most similar in the defense agents in their milks and the corresponding developmental delays in their immune systems. Defense factors in human milk include antimicrobial agents (secretory IgA, lactoferrin, lysozyme, glycoconjugates,oligosaccharides, and digestive products of milk lipids), antiinflammatory factors (antioxidants, epithelial growth factors, cellular protective agents, and enzymes that degrade mediators of inflammation), immunomodulators (nucleotides, cytokines, and antiidiotypic antibodies), and leukocytes (neutrophils, macrophages, and lymphocytes). Because of a lack of geographic/ethnic variation in the immunologiccomposition of human milk and corresponding immunologic delays in infants, these evolutionary processes seem stable. This is supported by investigations of diverse populations that indicate that this evolutionary outcome is highly beneficial to human infants.
Abbreviations: mya, millions of years ago; TNF, tumor necrosis factor
The extrauterine development of many components of the human immunesystem is delayed(1-14)(Table 1), and the delays partly explain why young infants are more susceptible to many types of infections and why the susceptibility increases with the degree of prematurity. Certain immunologic agents are transmitted either through amniotic fluid or via the placenta during fetal life. The risk of infections in newborn infants is, however, further lessened by human milkfeeding (15-17). Moreover, breast-feeding protects against gastrointestinal and respiratory infections well past the newborn period(18-23).
|Table 1. Examples of protective effects of some of the defense agents in human milk whose production is delayed in newborninfants|
A host of investigations performed over the past 40 y indicate that the protection is mainly due to defense agents in human milk, many of which are developmentally delayed in the infant (Table 1). The defense system in human milk is comprised of antimicrobial, antiinflammatory, and immunomodulating agents that are adapted to mucosal sites, are often multifunctional, and are not well...