Xenobiotics immune response

Details on the cellular immune responses occurring following the recognition of xenobiotic haptens as antigens by the immune system are described in chapters 33-35 of this volume. Ultimately, a certain combination of mediators is selectively activated and subsequently helps determine and differentiate the characteristic immune response (e.g., Thl vs. Th2). For example, dermal sensitizing chemicals (e.g., oxazolone and dinitrochlorobenzene) elicit a higher proportion of Thl cytokines such as IFNy and... 

Awareness of immunotoxicology was stimulated by a comprehensive review by Vos in 1977, in which he provided evidence that a broad spectrum of xenobiotics alter immune responses in laboratory animals and subsequently may affect the health of exposed individuals. Several additional reviews, as well as national and international scientific meetings, have reinforced these early observations. In several studies, alteration of immune function was accompanied by increased susceptibility to challenge with infectious agents or transplantable tumor cells, indicating the resulting immune dysfunction in altered host resistance. Clinical studies in humans exposed to xenobiotics have confirmed the parallelism with immune dysfunction observed in rodents. The latter sections in this volume describe studies with xenobiotics that resulted in immune modulation in rodents and man. 

In the additional functional (TIER-2) studies the immune system is more thoroughly investigated, while the animals are exposed to one or more doses of xenobiotics. Immune responses to several different types of antigens may be determined, including Tcell-dependent antigens like tetanus toxoid and ovalbumin, sheep red blood cells (SRBC) [38—41] and T cell-independent antigens like EPS [38,... 

Chemicals and pharmaceuticals may be tested for their capacity to induce skin sensitization [49]. The potency of a xenobiotic or pharmaceutical compound to induce delayed type hypersensitivity (DTH) or contact dermatitis (CD) may be tested in the so called local lymph node assay (LENA) in which the induction of an immune response in lymph nodes is determined after local (skin) exposure [49-51]. The induction of cellular proliferation in draining lymph nodes is measured by determining the... 

A recent paper clearly highlighted the limitations of in vitro systems in modeling whole-organism responses, which should be considered when developing biomarkers of in vivo toxicity. Dere and colleagues (58) compared the temporal gene expression profiles of Hepalclc mouse hepatoma cells and of the mice liver after treatment with a dioxin. The analysis revealed that Hepalclc cells were able to model the induction of xenobiotic metabolism in vivo. On the other hand, responses associated with cell cycle progression and proliferation were unique to the in vitro system, while lipid metabolism and immune responses were not replicated effectively in the Hepalclc cells. 

Xenobiotics can affect allergic disease in one of two ways. They can themselves act as antigens and elicit hypersensitivity responses, or they can enhance the development or expression of allergic responses to commonly encountered allergens, such as dust mite. Chemicals that act as allergens include certain proteins that can by themselves induce an immune response and low molecular weight chemicals (known as haptens) that are too small to induce a specific immune response but may react with a protein to induce an immune response that is then hapten specific. Haptens have been associated with both allergic contact dermatitis (ACD), sometimes called contact hypersensitivity... 

The general term hepatitis is used to describe conditions under which the liver becomes inflamed when liver cells that are damaged by a toxic substance, a substance that causes an immune response, or disease die, and their remnants are released to liver tissue. A number of toxicants can cause liver cell death. This is most damaging when it occurs through necrosis of liver cells, in which they rupture and leave remnants in the vicinity, which can lead to inflammation and other adverse effects. Dimethylformamide is a xenobiotic industrial chemical known to cause liver cell death ... 

General mechanisms by which xenobiotics may induce an immune response 134... 

Khan FD, Roychowdhury S, Gaspari AA, et al. Immune response to xenobiotics in the skin From contact sensitivity to drug allergy. Expert Opin Drug Metab Toxicol. 2006 2 261-272. 

Because the primary role of the immune system is the discrimination of self versus nonself, immunotoxic effects can occur in either direction. As such, immunotoxicology can be thought of as a continuum, which is depicted as the solid dark vertical arrow in Figure 1. A xenobiotic-induced change in immunocompetence from the normal range, which is manifest as an underactive immune system, is shown as a suppressed immune response , while a xenobiotic-induced change manifested as an over-... 

---