Immune Defences of Teleost Fish - Aquaculture Nutrition: Gut Health, Probiotics and Prebiotics - page 21

(Saunders and Magor 2004), although somatic hypermutation has been demonstrated (Flajnik
2002). This lack of isotype diversity (isotopy) is overcome by cross-linking of basic IgM
antibody subunits resulting in a range of antibody complexes: at least six structural isoforms
exist as a consequence of structural reorganization of basic monomer subunits into monomers,
dimers, trimers and tetramers (Sanchez and Dominguez 1991; Evans et al. 1998; Kaattari
et al. 1998). IgM is found in the cutaneous mucus of the Atlantic salmon, Salmo salar ,but
not in the gut mucus; indeed serum IgM, when added to gut mucus, was readily degraded by
proteolytic enzymes present (Hatten et al. 2001). Mucosal expression of antibodies has been
generally difficult to characterize. Fish do not express the classical mucosal antibody IgA;
however, recently a new third teleost Ig heavy chain isotype of antibody has been observed
as a specialized mucosal isotype which is secreted in mucus. These new antibodies have been
termed IgZ, IgT and IgF on the basis of being first described in mucosal secretions of zebrafish
Danio rerio (IgZ: Danilova et al. 2005; Flajnik 2005), rainbow trout (IgT: Hansen et al. 2005)
and fugu (IgF: Savan et al. 2005). In the common carp ( Cyprinus carpio ), however, two IgZ
subclasses have been described that display specific expression profiles which is suggestive
of unique humoral immune functions; where IgZ 1 is expressed in systemic organs (head
kidney, trunk kidney, spleen and PBLs in the blood) and IgZ 2 is expressed in the mucosa of
the gills and gut; both subclasses are transcribed as a membrane form and a secreted form
(Ryo et al. 2010). Challenges with the mucosal Lernea parasite were observed to induce
predominant expression of IgZ 2 , whereas the blood parasite Trypanoplasma borreli induced
IgZ 1 . These challenge expression studies are suggestive of functionality whereby IgZ 1 plays
a role in protection/immunity against blood parasites and IgZ 2 is protective against mucosal
parasites (Ryo et al. 2010). In addition, Ig expression is dependent on the route of challenge
by pathogens and their pathogenic antigens; studies investigating mucosal immunization of
carp resulted in specific antibody-secreting plasma cells in the mucosa of the gut and gills, and
no plasma cells were detected in the blood, head kidney or spleen. No such antibody-secreting
plasma cells were observed upon systemic immunization. Oral immunization with Vibrio
anguillarum antigens resulted in high numbers of plasma cells present in the gills (Rombout
et al. 1989c; Joosten et al. 1997; Cain et al. 2000; dos Santos et al. 2001).
Teleost humoral responses can be further compared to human and mammalian systems on
the basis of the existence of B cell subsets, responsiveness to PAMPs (generally recognized
by innate responses) and the ability to passively transfer immunity to fry. As with mammalian
systems, B cells and immunoglobulin production can be stimulated by both T cell-dependent
and T cell-independent antigens. In addition to pathogen-specific peptide antigens presented
by MHC and requiring T cell-dependent activation of B cells, the bacterial PAMP, LPS,
directly stimulates fish B cell proliferation and induction of antibody responses in the absence
of T cell involvement and memory (Dalmo and Seljelid 1995; Salati et al. 1987; Jakobsen
et al. 1999; Aakre et al. 1994; and reviewed in Swain et al. 2008). Indeed, vaccination of carp
with Vibrio anguillarum antigens, which are rich in LPS, induces IgM and IgZ 1 expression
in the head kidney and gut tissue, respectively (Ryo et al. 2010). Additionally, LPS has been
demonstrated to up-regulate mIgM-2, a novel membrane IgM isotype in zebrafish, widely
expressed in immune-related tissues such as the intestine, kidney and skin (Hu et al. 2011).
This T cell-independent, PAMP-activated B cell and antibody isotype-specific response is
suggestive of a distinct B cell subset analogous to the human B1 subset. Finally, due to the fact
that tailored adaptive responses take a relatively long time to be initiated and that development
of an immune repertoire in fish is slow, it is vital that some level of adaptive immune