Several more or less well-defined variables influence the development of productive mucosal immunity and oral tolerance, therefore constituting a complex and rather enigmatic mechanistic basis for adaptive immune defence and adverse immunological reactions to food. An inadequate epithelial barrier against luminal antigens is an important primary or secondary event in the pathogenesis of several mucosal diseases - being influenced by the individual's age (e.g. preterm versus term infant), activation of the epithelium and subepithelial elements, such as APCs and mast cells (e.g. by infection, cytokines or neuropeptides), and the shielding effect of SIgA provided by breast milk or produced by adaptive B-cell responses in the infant's gut. The consequences will depend on how quickly mucosal homoeostasis can be attained or re-established after abrogation.

SlgA is the best-defined effector component of the mucosal immune system, and this first-line specific defence against infectious agents and other harmful substances is of considerable clinical interest. The large capacity for storage of pIgA in the mammary-gland epithelium and duct system explains the remarkable output of SIgA during feeding. Breast milk also contains an array of important immunoregulatory factors and promotes colonization of lactic acid-producing bacteria. These members of the indigenous microbiota are powerful in combating pathogenic intruders that may break oral tolerance (Collins and Gibson, 1999; Isolauri et al., 2001), and they also appear to exert a beneficial effect on the cytokine balance of the host and thereby on the developing immunological responder phenotype (Fig. 14.9). Animal experiments have indeed documented that the commensal bacterial flora is crucial both for the induction of oral tolerance and for its re-establishment after abrogation (Helgeland and Brandtzaeg, 2000). Altogether, this effect might not only be mediated through immune modulation, but could also be explained by the

Fig. 14.9. Multiple direct or indirect effects of breast-feeding may be imprinted in the immune-responder phenotype of the infant. Details are discussed in the text. (Modified from Hoppu et al., 2001.)

enzymatic activity of the indigenous flora that degrades food proteins to tolerated peptides (Barone et al., 2000).

Convincing evidence exists for an important role of breast-feeding in the defence against mucosal infections. Its role in oral tolerance and protection against food allergy has been much more difficult to establish conclusively. This is not surprising in view of the complex and poorly understood interface between these two enigmatic biological phenomena, with multiple potential interactions influenced by the numerous bioactive components of breast milk (Fig. 14.9). For ethical reasons, it will not be possible to assign infants to breast-or formula-feeding for long-term follow-up studies. Therefore, perhaps we shall just have to take it on trust that exclusive breast-feeding for several months, followed by mixed feeding, is the natural way to begin life for all mammals, including humans.

Gluten Free Living Secrets

Gluten Free Living Secrets

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