Page 516 - The Toxicology of Fishes

496 The Toxicology of Fishes

1993), and Atlantic salmon (Salmo salar) (Reite and Evansen, 1994) have been found to degranulate
upon inoculation with certain noxious or infectious agents. Degranulation in tilapia was correlated with
increased neutrophil migration to the injection site, suggesting that fish eosinophils may be analogous
to mammalian mast cells (Matsuyama and Iida, 1999).

Nonspecific Cytotoxic Cells
Many teleost species possess immune cells involved in spontaneous, nonspecific cytotoxicity against
transformed mammalian cells, parasites, and viral/bacterially infected cells (Evans and Jaso-Friedmann,
1992; Secombes, 1996; Shen et al., 2002). A cell surface marker (isolated from catfish) found to be
important in teleost NCC activity appears to be conserved between mammalian species and fish (Jaso-
Friedmann et al., 1997, 2001). Nonspecific cytotoxic cells are usually found in the head kidney, spleen,
and blood (Evans and Jaso-Friedmann, 1992); circulating NCCs are morphologically and functionally
distinct from those of the pronephros and spleen (Hogan et al., 1996; Shen et al., 2002).

Adaptive Immune Defense

Adaptive (acquired) immunity in mammalian species involves: (1) recognition of foreign, non-self entities
by antigen-specific lymphocytes, (2) proliferation and differentiation of antigen-specific lymphocyte
clones, and (3) memory and enhanced response upon subsequent exposure to antigen (due to greater
numbers of antigen-specific lymphocytes). The nature of the adaptive immune response depends upon
the activation of either T-lymphocytes (i.e., cell-mediated immunity) or B-lymphocytes (i.e., humoral
immunity). Teleost fish possess the genetic machinery necessary to mount both humoral- and cell-
mediated immune responses (Kaattari and Piganelli, 1996; Manning and Nakanishi, 1996). This includes
genes encoding recombination activating genes (RAGs) (Willett et al., 1997), major histocompatibility
complex (MHC) class I and II (Stet et al., 1998), T-cell receptors (TCRs) (Haire et al., 2000; Partula et
al., 1999; Wermenstam and Pilstrom, 2001; Wilson et al., 1998; Zhou et al., 1997), immunoglobulin
heavy and light chains (Pilstrom and Bengten, 1996), cytokines (Secombes et al., 1999), and various
immune coreceptors (Hansen and Strassburger, 2000; Yoder et al., 2001). In addition, the functional
equivalents of antigen presenting cells (APCs) are present in fish (Miller et al., 1994; Vallejo et al., 1991,
1992). Fish species have also been shown to exhibit antigen-specific antibody production (Kaattari and
Piganelli, 1996), cytotoxic T-lymphocyte (CTL) activity (Stuge et al., 2000; Verlhac et al., 1990; Yoshida
et al., 1995), mixed-lymphocyte responses (Miller et al., 1986), delayed hypersensitivity (Manning and
Nakanishi, 1996), graft-vs.-host reactions (Nakanishi, 1994), and xenograft/allograft rejection (Manning
and Nakanishi, 1996).

Humoral Immunity
The development of teleost immune cell lines has greatly advanced our understanding of the fish humoral
response (Miller et al., 1998). B-lymphocytes of fish express both B-cell receptors (BCRs) and secreted
forms of IgM. Cross-linking of BCRs results in protein tyrosine phosphorylation, calcium ion influx,
and B-lymphocyte proliferation (Van Ginkel et al., 1994). Elicitation of anti-hapten responses to T-lym-
phocyte-independent antigen in catfish has been shown to require APCs and B-lymphocytes but not
T-lymphocytes (Miller et al., 1985). The requirement for APCs (i.e., MØs) in this response is due to
the need for IL-1 release (Ortega, 1993). In addition, responses to T-lymphocyte-dependent antigens
appear to require the presence of T- and B-lymphocytes along with APCs. The T-lymphocyte-dependent
response requires that antigen be processed by APCs prior to elicitation of the response. The role that
MHC molecules play in humoral immunity in fish has yet to be clearly defined (Vallejo et al., 1990).
Various effector mechanisms have been described for teleost antibody, including neutralization, opsoniza-
tion, complement fixation, precipitation, and agglutination (Kaattari and Piganelli, 1996). In addition,
protective antibodies against bacterial and viral pathogens are produced following immunization.
Although teleosts do not appear to possess a secondary humoral response as dramatic as that seen in
mammals, secondary exposure of fish to sub-immunogenic doses of an antigen elicits a significantly
greater response compared to that observed following the initial exposure (Arkoosh and Kaattari, 1991).