Immune Defences of Teleost Fish - Aquaculture Nutrition: Gut Health, Probiotics and Prebiotics - page 33

epithelial cells and macrophages, acting as conventional APCs that process and present
antigenic peptides in an MHC-restricted manner, capable of mounting specific adaptive
immune responses. The intestinal mucosa is indeed a first-line defence system which involves
the recognition and processing of antigen. This mucosal surface exists in folds rather than
villi, as this tissue lacks the lacteals characteristic of villi and, in addition, does not have a
lymphatic system, lymph nodes or Payer's patches or lymphoid follicles. As a result, the
GALT is rather diffusely distributed in the intestinal mucosa and it is likely that antigenic
priming of responses takes place at the site of invasion. Thus, all the important cells of the
immune system are generally present in the tissue rather than relying on transport of antigen
or cells in and out of the infected site (Zapata and Amemiya 2000; Bernard et al. 2006a;
Huttenhuis et al. 2006). The relatively high expression of MHC II in the gills and in the
second segment of the mid intestine is suggestive that these are the major mucosal sites for
antigen processing and presentation to prime adaptive responses. In addition, these sites have
been described to include both dendritic-cell-like APCs and lymphocytes (Koppang et al.
1998; 2003). A recent study by Fuglem et al. (2010) sought to further define antigen-sampling
cells in the second segment of the mid intestine. Due to the relatively low glycocalyx level in
salmonids, they investigated the uptake of gold-labelled bovine serum albumin (gold-BSA)
by the gut of Atlantic salmon and rainbow trout. The uptake of gold-BSA was restricted to a
small number of specialized epithelial cells which were located in the mucosal folds of the
second segment of the mid intestine and to dendritic-like cells which were shown to project
dendrites through the tight junction between epithelial cells and to extend into the lumen
enabling the cell to sample luminal contents. In addition, morphological studies coupled with
lectin binding demonstrated that the specialized epithelial cells resembled the phenotype of
immature mammalian M cells. This study is of great value as it demonstrated that teleost fish
possess both antigen sampling cells and sampling mechanisms similar to those understood
for the systems in mammals/humans. By inference from our understanding of these immune
systems, it is reasonable to suggest that these antigen-sampling cells play similar roles in
immune tolerance versus immune activation decisions as those in their higher counterparts.
These immune decisions are made by the presence or absence of danger signals (signals
derived from pathogens or from host tissue breakdown) detected by their cognate pattern
recognition receptors, predominantly TLRs (see Section 2.2). As a consequence of recognition
of danger signals, co-stimulatory molecules are likely to be up-regulated on APCs. Indeed,
the co-stimulatory molecule B7, and its T cell counterparts CD28 and CTLA-4, have been
described as expressed in teleost fish (Hansen et al. 2009; Bernard et al. 2006b) and, like the
human immune system, B7 has several homologous forms which may both positively and
negatively regulate T cell activation through ligation of the CD28 receptor or CTLA-4.
Integral to the efficient functioning of gut mucosa is the ability to discriminate between
self, beneficial non-self and harmful non-self. The gut is required to gain nutrients from an
environment that is full of food-derived antigens, commensal organisms and pathogenic organ-
isms; inappropriate immune activation to beneficial non-self would result in inflammation of
the gut, a failure to efficiently digest food and absorb required nutrients, and hence a failure
to thrive. The gut has developed sophisticated mechanisms capable of responding to harm-
ful pathogenic non-self, while maintaining the capability to switch off or suppress potential
immune responses directed against beneficial non-self antigens. Oral tolerance is a mechanism
characteristic of intestinal immunology where repeated mucosal immunization and antigenic
challenge result in immune hyporesponsiveness or suppression. It must be noted, however,