Date of Award

1-1-2009

Degree Name

Doctor of Philosophy

Department

Zoology

First Advisor

Halbrook, Richard

Abstract

This dissertation summarizes three investigations in which immunosuppressive effects of environmentally relevant concentrations of dietary methylmercury (MeHg) were assessed in adult non-breeding male kestrels, female kestrels during egg laying, and nestling kestrels. Immunological endpoints included cell-mediated immunity (CMI) using the phytohemagglutinin (PHA) skin-swelling assay and antibody-mediated immune function using the sheep red blood cell (SRBC) hemagglutination assay. Hematology profiles were evaluated over time in adult males and nestlings to monitor immunological and physiological status of kestrels. Primary and secondary immune system organs were examined histopathologically to identify T and B cell-dependent structural changes related to immunosuppressive effects of MeHg. Male kestrels dosed with 3.9 µg/g MeHg in the diet for 13 weeks exhibited suppression of CMI (p = 0.019), elevation in the proportion of heterophils (p < 0.001) and total white blood cell counts (p < 0.001), and a decline in the proportion of peripheral blood lymphocytes (p < 0.001). Primary antibody-mediated immune response was suppressed at 0.6 µg/g MeHg (p = 0.014), but secondary immune function was not adversely effected. Female kestrels were dosed with 2.8 µg/g MeHg in the diet for 13 weeks prior to egg laying and exhibited a higher primary immune response to sheep red blood cells (SRBC) than controls (p = 0.013). Subtle reproductive effects were also apparent including a 4.3-day delay in egg laying (p < 0.001) and depletion of egg mass (p = 0.037), egg volume (p = 0.050), and eggshell thickness (p = 0.004). The quantity of antibody production during egg laying, as measured by anti-SRBC antibody concentrations in egg yolk, did not differ from controls. However, the duration of antibody production was significantly longer for MeHg dosed females (p = 0.007), suggesting immunomodulation occurred among dosed kestrels during egg laying. Nestlings dosed with 0.6 and 3.9 µg/g in the diet for 25 days post-hatch also exhibited suppression of CMI at 11 days of age (p = 0.004) and lymphoid depletion in spleen (p < 0.001) and thymus tissue (p = 0.017). Antibody-mediated immune function was not adversely affected in nestling kestrels. Results from these three investigations suggested suppression of CMI and lymphoid depletion occurred at a dose concentration of 3.9 µg/g MeHg in adult, non-breeding male kestrels and at both 0.6 and 3.9 µg/g MeHg dose concentrations in nestlings. Immunosuppressive effects and immune dysfunction with respect to antibody-mediated immune function occurred at a dose concentration of 2.8 µg/g in female kestrels during egg laying; estrogen-disrupting characteristics of MeHg during avian reproduction cannot be excluded as a potential influence on this response. Immunotoxic effects of dietary MeHg in female kestrels during egg laying were primarily immunosuppressive and targeted T cell-mediated immune function. Cell-mediated immunity was highly sensitive to the immunosuppressive effects of dietary MeHg at low, environmentally relevant exposure concentrations, and at comparatively high doses (> 3 ppm) at which reproductive effects have been demonstrated in kestrels in other investigations.

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