Immune Defences of Teleost Fish - Aquaculture Nutrition: Gut Health, Probiotics and Prebiotics - page 34

that conditions stressful to the fish, such as environmental changes (temperature, pH etc.) and
predation, can result in breaking of tolerance and the elicitation of inappropriate inflammatory
immune responses that are potentially harmful to the gut tissue and hence digestive processes.
Mucosal tolerance has been described in teleost fish (Davidson et al. 1994; Piganelli et al.
1994) where repeated challenge by bacterial antigens resulted in suppression of antibacte-
rial antibody responses. In addition to mucosal oral tolerance induced by mucosal alloantigen
challenge being demonstrated for immunoglobulin production, tolerance induction has been
observed for suppression of cell cytotoxicity which was reversible upon systemic adminis-
tration of the same alloantigenic challenge (Sato and Okamoto 2007). Thus, mucosal/oral
tolerance mechanisms characterized in teleost fish display antigen specificity and result in the
suppression of both CD8 + T c and CD4 + T h involved in CMI and humoral responses. These
mechanisms of suppression, like the human immune system, may involve clonal deletion by
apoptosis and regulation by T reg ; both of these mechanisms are determined by the nature and
concentration of antigen being presented.
Mucosal tolerance arises not only as a consequence of T cell suppression (either by
clonal deletion or by suppression by T reg ) but also through regulatory mechanisms involving
innate immunity. Such mechanisms may involve TLR down-regulation on epithelial cells
and macrophages and induction of negative regulators of TLR signalling such as Tollip and
splice variants of adaptor proteins; such receptors and their adaptors have been described
in teleost fish (Jault et al. 2004; Rebl et al. 2008; and reviewed in Purcell et al. 2006 and
Aoki et al. 2008). In addition, it is possible that peptidoglycan recognition by teleost fish
homologues of NOD2 may also regulate innate immune responses (Stein et al. 2007).
Such modulatory responses would suppress or modulate both cytokine and co-stimulatory
(B7) molecule expression by APCs. Thus, mucosal tolerance mechanisms of the innate
immune system will also impact on adaptive immune tolerance. As a result of regulation
of both innate and adaptive responses, mucosal tolerance is likely to be initiated in both an
antigen-dependent and an antigen-independent manner to specific pathogens, or indeed a
broad range of pathogenic microbes. The full characterization of such potential regulatory
mechanisms in teleost fish is likely to elucidate the use of pathogen-specific vaccines and
microbial PAMPs and commensal organisms in protection against aquatic pathogens and
their resulting pathological consequences.
The mucosal response is dominated by tolerance in healthy homeostatic conditions which
allow the fish to gain benefit from commensal organisms and dietary non-self. It is vital,
though, that non-tolerogenic adaptive responses are initiated to harmful or pathogenic non-self.
In the presence of such pathogens, the host is capable of modulating mucosal tolerance mech-
anisms to those of humoral and cell-mediated adaptive responses that protect teleosts from
extracellular- and intracellular-resident pathogens respectively. With respect to extracellular
and surface protective immunity, mucosal antibodies secreted into mucus are different com-
pared to systemic immunoglobulin. Analysis of cutaneous mucosal immunoglobulin revealed
the isotype to be IgM-like and showed that variation in antibody types in mucus resulted by
oligomerization of IgM forms rather than isotypes (Wilson and Warr 1992; Hatten et al. 2001;
Morrison and Nowak 2002). Due to the proteolytic environment present in the gut and the
potential for antibody degradation, it is not clear as to whether IgM is expressed in gut mucus.
Integral to mucosal immune function, fish express pIgR in mucosal tissues. This receptor is
expressed by mucosal epithelial cells which allows for the binding of mucosal immunoglobulin