K. Haverson

The mucosal immune system fulfils the primary function of defence against potential pathogens that may enter across vulnerable surface epithelia. However, a secondary function of the intestinal immune system is to discriminate between pathogen-associated and 'harmless' antigens, expressing active responses against the former and tolerance to the latter. Control of immune responses appears to be an active process, involving local generation of IgA and of regulatory and/or regulated T lymphocytes. Two important periods of maximum exposure to novel antigens occur in the young animal, immediately after birth and at weaning. In both cases the antigenic composition of the intestinal contents can shift suddenly, as a result of a novel diet and of colonisation by novel strains and species of bacteria. Changes in lifestyles of man, and husbandry of animals, have resulted in weaning becoming much more abrupt than previously in evolution, increasing the number of antigens that must be simultaneously evaluated by neonates. Thus, birth and weaning are likely to represent hazard and critical control points in the development of appropriate responses to pathogens and harmless dietary and commensal antigens. Neonates are born with relatively undeveloped mucosal immune systems. At birth this factor may prevent both expression of active immune responses and development of tolerance. However, colonisation by intestinal flora expands the mucosal immune system in antigen-specific and non-specific ways. At weaning antibody to fed proteins can be detected, indicating active immune responses to fed proteins. It is proposed that under normal conditions the ability of the mucosal immune system to mount active responses to foreign antigens develops simultaneously with the ability to control and regulate such responses. Problems arise when one or other arm of the immune system develops inappropriately, resulting in inappropriate effector responses to harmless food proteins (allergy) or inadequate responses to pathogens (disease susceptibility).

European-wide directives are in place to establish a sustainable production of pigs without using production enhancers and chemotherapeutics. Thus, an economically-viable pig production is now only possible when the physiological mechanisms of defense against pathogens and tolerance against nutrients and commensal bacteria in the intestinal immune system are taken into account. During the postnatal period the piglet is facing first the time large amounts of new antigens and at weaning a second wave of nutritional antigens is entering the intestinal tract. The appropriate development of humoral and cellular functions of the intestinal immune system is essential for optimum growth and performance of the piglets. The integrity of the intestinal surfaces is a prerequisite of intestinal immunity and tolerance. Secretory IgA serves to exclude harmful antigens from uptake. The induction of intestinal immune reactions starts with antigen presentation by professional antigen presenting cells of Peyer's patches and mesenteric lymph nodes. In addition, the intestinal lamina propria serves as a mucosal compartment for regulation of immune responses. Here especially T regulatory cells (CD4(+) CD25(+)) have their function for maintaining intestinal homeostasis. The network of mucosal T and B cells develops after birth in a programmed sequence; it is almost completed at week 7 after birth. Weaning is associated with changes in the regulation of the lymphoid cells in the mucosa. In small and large intestine increases in pro- and anti-inflammatory cytokines were observed after weaning in lymphocytes. Epithelial cells were studied both in intestinal samples and in vitro. Here the cytokine patterns provide evidence that weaning is inducing a transient inflammation of the mucosa. Piglets weaned under conventional conditions have a thicker mucosa than pigs weaned from isolators. Cells of isolator-reared pigs show slightly higher levels of activation markers - probably reflecting the interaction of the foreign protein derived from bovine milk. The results presented in this overview demonstrate that further effort is necessary to elucidate the function of the porcine intestinal immune system in the postnatal period and at the time of weaning to provide criteria for porcine intestinal health.