Employing a variety of in vivo and in vitro techniques, 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 mechanisms of action at the cellular and molecular levels; (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 immunotoxic endpoints. 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 articular, thymic maturation; (b) Development and utilization of model systems which allow assessment of skin immunity [i.e., keratinocytes]. Endpoints for these assessments include production of soluble mediators (cytokines), surface markers and effector cell function; (c) Implementation of a model system to examine the participation of cytokines in chemical-induced hepatotoxicity; (d) Examination of the mechanisms of chemical-induced thymic atrophy with particular emphasis on apoptotic mechanisms (programmed cell death); (e) Examining the control of cytochrome P450c and the TCDD-inducible or tumor associated aldehyde dehydrogenase in selected rat immune cell and lymphoid organs; (f) Efforts are being taken in which immunodeficient mice are being """"""""restored """""""" with immune cells from humans; and (g) Statistical evaluation of the immunotoxicology database.
