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invertebrates. The immunological defenses of invertebrate aquatic species such as mol-
lusks, crustaceans, sponges, and oligochaetes rely mainly on nonspecific innate immunity
accompanied by antimicrobial peptides. The nonspecific immune response is the first line
of defense against potential pathogenic organisms and includes phagocytosis, oxidative
burst, cytotoxic activity, inflammatory reactions, and soluble mediators such as enzymes,
antimicrobial peptides, and cytokine-like molecules.
Immunotoxicology, albeit a young science, is a rapidly expanding discipline that studies
the deleterious effects of xenobiotics on the immune system. Substantial efforts have now
been made in terms of the harmonization and validation of experimental approaches and
methodologies to perform immunotoxicity studies (Brousseau et al. 2005) and to identify
immunological responses that are sensitive to a large spectrum of xenobiotics in order
to define immunological biomarkers. These efforts will serve as benchmarks for com-
parison with emerging high-throughput assays such as gene expression, proteomics, and
metabolomics. In addition, harmonization of these techniques will also promote recogni-
tion for environmental risk assessments by both the national and international regulatory
community.
Studies establishing the links between the effects of environmental contaminants on the
immune system and the reduction of the host's resistance to infections or the development
of cancer are the keystone of immunotoxicology, defined as the study of direct or indirect
alterations of the immune system occurring as a result of exposure to chemicals such as
pharmaceuticals, recombinant biological or environmental and occupational pollutants
(Dean et al. 1979; Luster et al. 1988). A good correlation exists between changes in immu-
nity tests and altered host resistance, since there have been no instances where host resis-
tance was altered without affecting these tests. However, in some cases, immune changes
can occur without corresponding alterations in host resistance that are perceived as early
adaptative responses to stress (Luster et al. 1992a, 1992b, 1993). A “three-tier” approach was
therefore recommended in which Tier 1 includes screening assays that would likely detect
immunotoxic xenobiotics; Tier 2 allows the definition of the immune component(s) affected
as well as the establishment of effects on host resistance; Tier 3 provides, in very general
terms, approaches that could be used to identify the mode of action of the chemicals on
the immune system (Dean et al. 1979; Luster et al. 1988). Subsequently, the sensitivity of
various immune tests and the degree to which they agree with the commonly used host
susceptibility tests has been addressed in order to define the immune correlate of adverse
effects on host's resistance to infections and cancers (Luster et al. 1992a, 1992b, 1993; Luster
and Gerberick 2010). These studies lead to the concept of immunological biomarkers or
“immunomarkers” (Pillet and Nicolas 2005). From the ecological risk assessment perspec-
tive, biomarkers that cannot only predict impacts on the health status of the individual but
also at the population levels are perceived as having added value. In a field study with wild
clam ( Mya arenaria ) populations, specimens collected at sites with lower clam density and
growth index had significantly higher levels of lipid peroxidation (a marker of inflamma-
tion), vitellogenin-like proteins, and metallothioneins (Blaise et al. 2003). Moreover, clams
collected at polluted sites had fewer young, suggesting important changes in population
structure. In another case, an extensive multibiomarker study revealed that the population
metrics of M. arenaria living in polluted sites were more strongly related with phagocytosis
in addition to energy status and sensitivity to temperature changes (Gagné et al. 2008a).
The development of immunotoxicology has revealed that contaminants can impact the
immune system in the environment. Trace metals and organic pollutants, including poly-
chlorinated biphenyls (PCBs), polychlorinated dibenzo- p -dioxins (PCDDs), a number of pes-
ticides and more recently polybrominated diphenyl ethers (PBDEs), have been shown to alter
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