Use of Contact Hypersensitivity in Immunotoxicity Testing

Abstract

The histopathological examination of lymphoid organs together with a T-dependent antibody (TDAR) assay are the primary components of preclinical immunotoxicity assessment. Additional testing including measurement of cellular immunity may be considered. Besides ex vivo lymphocyte proliferation assays, either delayed or contact hypersensitivity models can be used. Contact hypersensitivity testing is typically performed either in mice or in guinea pigs and is directly derived from classical models used for the detection of contact sensitizing chemicals. Whatever the selected model, it is comprised of a sensitizing phase where the animals are applied a strong contact sensitizer topically, then a rest phase, and finally an eliciting phase where sensitized animals are challenged topically with the same contact sensitizer.In mice, the ear-swelling test is the reference procedure in which mice are sensitized to the ear or shaved abdominal skin and then challenged on the ear. Ear swelling usually measured from ear thickness reflects a cell-mediated immune response. In guinea pigs, a strong sensitizer is applied on the shaved skin of the abdomen or the interscapular area. The sensitized animals are challenged on another area of the shaved abdomen, and the cell-mediated response is assessed semiquantitatively from the magnitude of induced erythema inconsistently associated with edema. Treatment or exposure with immunosuppressive chemicals can result in a significantly decreased ear swelling or skin reaction. Contact hypersensitivity models are seldom used nowadays in preclinical immunotoxicity testing, most likely because of the lack of standardization and extensive validation as well as their use being restricted to mice or guinea pigs.

The environment as a driver of immune and endocrine responses in dolphins (Tursiops truncatus)

“…Natural killer (NK) cells play an important role in innate immunity by lysing and killing nonself/foreign cells, tumor cells and virus-infected cells [ 43 ]. Their activity is another commonly measured functional component of the innate immune response [ 43 , 44 ]. Although the two-managed care dolphin groups (MMP, GA) differed in closed/ semi-open vs open systems, there were no significant differences in their absolute numbers of MHCII+ cells, CD4+ helper T cells, CD21 B cells-mature and NK cell and lysozyme activity.…”

Immunotoxic effects of sodium tungstate dihydrate on female B6C3F1/N mice when administered in drinking water

“…MCH was increased (4%) at 125 mg STD/L, and decreased (4%) at 250 and 500 mg STD/L; MCHC was decreased 5% with 500 mg STD/L. The effects on hematology are minimal and not sufficiently significant to contribute to the assessment of direct immunotoxicity (Descotes, 2004). …”