The Immunotoxicology Group studies the adverse effects on the immune system resulting from occupational, inadvertent, or therapeutic exposure to drugs, environmental chemicals, and biological materials. The ongoing objectives include efforts: (1) to evaluate and examine the influence of selected drugs or environmental chemicals on the immune response and relate alterations in immunological functions with general and specific organ toxicity; (2) when applicable, to examine potential mechanism of action; (3) to relate changes in immunological functions with altered host resistance following challenge with tumor cells or infectious agents; and (4) to refine and validate a panel of immune and host resistance procedures in order to better define immunotoxicity and correlate changes in immune function with altered host resistance. General methodology employed includes various cell and tissue culture procedures, flow cytometry, electrophoresis (northern and western blots), hematological procedures and biochemical tests to determine the activity of immune cells. Studies have been conducted in the following areas: (a) Development and utilization of procedures to examine the effects of in utero exposure to selected environmental chemicals on the developing immune system in mice and, in particular, thymic maturation; (b) Development and utilization of model systems which allow assessment of specific macrophage populations [i.e., alveolar (lung) and Langerhans (skin) cells]. Endpoints for thee assessments include production of soluble mediators (monokines), surface markers and effector cell function; (c) Examination of the mechanisms of chemical-induced thymic atrophy with particular emphasis on apoptotic mechanisms (programmed cell death); (d) Examining the control of cytochrome P450c and the TCDD-inducible or tumor associated aldehyde dehydrogenase in selected rat immune cell and lymphoid organs; (e) Examining the mechanism(s) associated with increased endotoxin sensitivity following exposure to selected compounds including T-2 toxin and TCDD.
