Effects of early environment on mucosal immunologic homeostasis, subsequent immune responses and disease outcome

During the neonatal period, the mammalian host is exposed through mucosal surfaces for the first time to a plethora of environmental macromolecules and microbial agents. The neonatal mucosa is endowed with all major elements of innate and adaptive immunologic repertoire. Rudimentary Peyer's patches and mucosal lymphoid follicles expressing HLA-DR+ and CD4+ cells can be observed as early as 10-11 weeks of gestation. CD5+ and IgA+ B cells can be detected in Peyer's patches by 16-18 weeks. CD7+ CD3+ T lymphocytes have been observed in fetal Peyer's patches, epithelial surfaces as well as in the lamina propria. Interestingly, however, the early neonatal period is also characterized by a relative deficiency in antigen-presenting cell functions, altered cell-mediated immune responses, and a relative increase in apoptosis and eosinophilic responses. After birth, each human being may be colonized by over 100 trillion bacteria, representing over 500 bacterial species. The ratio of bacterial to human cells in a normal adult may exceed 10:1. The nature and the species of microflora acquired in the first few months of life is determined by many factors including, external environmental microflora, introduction of cow's milk, use of antibiotics and immunomodulatory agents, and use of breastfeeding. Recent Investigations have shown that the nature of mucosal microflora acquired in early infancy determines the outcome of mucosal inflammation and the subsequent development of mucosal disease, autoimmunity and allergic disorders later in life. It appears that altered mucosal microflora in early childhood alters signaling reactions which determine T cell differentiation and/or the induction of tolerance. Reduced Th1 and increased Th2 cytokine expression in the respiratory tract associated with increased allergic disease has been correlated with reduced exposure to microbial agents associated with Th1 responses. In contrast, reduced exposure to helminthes in the gut associated with reduced Th2 expression appears to correlate well with dominant Th1 cytokine expression and inflammatory bowel disease. These observations suggest that the nature of interaction between the external environment and the mucosal tissues in the early neonatal period and infancy may be critical in directing and controlling the expression of disease-specific responses in later life.