Page 513 - The Toxicology of Fishes

The Immune System of Fish: A Target Organ of Toxicity 493

Numerous studies have described antigen uptake in the teleost gut (Robohm and Koch, 1995; Rombout
et al., 1985), skin, and gills (Moore et al, 1998; Ototake et al., 1996; Tatner et al., 1984; Zapata et al.,
1986). Oral and bath/immersion vaccinations have been observed to yield a differential response in the
specificity of mucus and serum antibodies without any observable isotypic difference between the
secretory and serum antibody molecules (Kaattari and Piganelli, 1996). Investigators have also observed
a phenomenon similar to mammalian oral tolerance in rainbow trout (Oncorhynchus mykiss) following
oral antigen exposure (Jones et al., 1999).

Nonspecific Immunity

Nonspecific mechanisms of an immune response in teleosts include both soluble and cellular components.
Soluble constituents are mainly evolutionarily conserved molecules that have broad cross-reactivity,
recognizing molecular motifs shared by a wide variety of microorganisms. Nonspecific soluble molecules
described in this chapter include complement, acute-phase proteins, and lysozyme. Although cytokines
(i.e., interferons, interleukins, tumor necrosis factors, and transforming growth factors) are involved in
the regulation of both innate and adaptive immune responses, they are included in this section for
simplicity. Cellular components of the nonspecific immune response involved in maintaining internal
homeostasis by removing dead or unwanted cells include MØs, granulocytes, and NCCs.

Soluble Components
Complement
The complement system of fish has been reviewed (Sakai, 1992; Sunyer and Lambris, 1998; Yano, 1996).
Virucidal, bactericidal, parasiticidal, opsonic, and chemotactic activities of complement components
have all been described in teleost species (Yano, 1996). Many teleost fish have been found to possess
classical, alternative, and lytic complement components similar to those of mammals. Proteins involved
in the lectin-activated pathway have also been described (Endo et al., 1998; Nagai et al., 2000; Nonaka
and Smith, 2000). Interestingly, the alternative complement pathway of several fish species are much
more pronounced than those described for mammals, suggesting a greater importance for this pathway
in fish immune defense (Sunyer et al., 1996; Yano, 1996). Teleosts have been found to possess a more
diverse array of complement components than higher vertebrates (Sunyer et al., 1998); for example,
multiple C3 forms have been described for rainbow trout (Oncorhynchus mykiss) (Sunyer et al., 1996),
sea bream (Sparus aurata) (Sunyer et al., 1997), and carp (Cyprinus carpio) (Nakao et al., 2000), and
there is evidence that these isoforms are the products of separate genes. Additionally, due to the presence
of a molecule that shares characteristics of both C2 and factor B in bony fish, the emergence of separate
molecules appears to have occurred following the divergence of teleost species from the tetrapod line
(Kuroda et al., 1996; Seeger et al., 1996; Sunyer et al., 1998).

Interferon
Evidence for the presence of interferon (IFN) in teleosts has been reviewed (Yano, 1996). Teleost IFN
activity was originally described in cell culture (Gravell and Malsberger, 1965) and by studies in rainbow
trout (Oncorhynchus mykiss), demonstrating the induction of a protein with antiviral and MØ activating
factor properties (Graham and Secombes, 1990). Recently, sequences of IFN-like genes have been
identified in zebrafish (Danio rerio) (Altmann et al., 2003) and catfish (Ictalurus punctatus) (Long et al.,
2004). Induction of antiviral fish Mx proteins by viral infection and poly I:C incubation has also been
demonstrated (Lee et al., 2000; Nygaard et al., 2000; Trobridge and Leong, 1995; Trobridge et al., 1997).

Interleukins
Interleukins (ILs) are small molecules involved in the regulation of both innate and adaptive immunity
in mammals (Kaiser et al., 2004). Recently, considerable effort has been directed toward the elucidation
of interleukin genes in fish species (Secombes and Cunningham, 2004; Secombes et al., 1996, 2001).
Mammalian IL-2 is a potent growth factor. Although media from activated fish leukocyte cultures have