Immunotoxicity mechanisms

Inflammatory responses Immunotoxic mechanisms production and modulation of proinflammatory cytokines with ROS overproduction Enhanced inflammation and tissue damage where immune cell mobilization occurs Pb in rat brain produces neutrophil-derived inflammation and apoptosis Chetty et al. (2005), Kibayashi et al. (2010)... 

In addition to effects mediated through glucocorticoid secretion (stress-related), a hypothetical mechanism for direct immunotoxicity of organophosphates is the inhibition of esterases and stabilization of the lysosomal membrane of lymphocytes, thus blocking release of lymphokines (Sharma and Reddy 1987). 

Some animal studies indicate that dietary exposure to methyl parathion causes decreased humoral and cellular responses (Shtenberg and Dzhunusova 1968 Street and Sharma 1975). A more recent, well-designed animal study that included a battery of immuno/lymphoreticular end points showed few effects at the nonneurotoxic doses tested (Crittenden et al. 1998). No adequate studies are available in humans to assess the immunotoxic potential of methyl parathion. Therefore, studies measuring specific immunologic parameters in occupationally exposed populations are needed to provide useful information. Further studies are also needed to investigate the mechanism for methyl parathion-induced immunotoxicity since this information would help to identify special populations at risk for such effects. 

A number of studies have also involved the use of microarrays as tools for the evaluation of mechanisms of immunotoxicology. For example, toxic effects of ricin,23 hexachlorobenzene,24 and nickel,25 revealed an unexpected role for inflammatory processes. These findings illustrate the value of microarray analysis in identifying inflammation as a mechanism involved in the toxicopathology following exposure to a particular compound and highlight the underestimated importance of inflammatory processes in immunotoxicity. 

FUNCTIONAL FLOW CYTOMETRY FOR EVALUATION OF IMMUNOTOXICITY AND MECHANISM OF ACTION... 

Dudley, A.C., et al., An aryl hydrocarbon receptor independent mechanism of JP-8 jet fuel immunotoxicity in AH-responsive and AH-nonresponsive mice, Toxicol. Sci., 59 251, 2001. 

Several comprehensive reviews of the immunotoxicity of TCDD have been published.13 Therefore, the goal of this chapter is to highlight the most recent developments in the field, with particular attention given to studies that provide new insight into the possible cellular and molecular mechanisms of PHAH immunotoxicity. New data that address three less-studied aspects of TCDD immunotoxicity will also be reviewed, including altered innate responses, toxicity to the developing immune system, and deregulation of anamnestic immune responses. 

Kerkvliet, N.I., Recent advances in understanding the mechanisms of TCDD immunotoxic-ity, Int. Immunopharmacol., 2, 277, 2002. 

This chapter presents specific information with regard to the effects of environmental and occupational exposure to arsenic on inflammatory processes, the immune system, and host defense. While the focus is on the in vivo and in vitro effects of arsenic on host immune responses (e.g., immunotoxicity and hypersensitivity) and their relationship to clinically observed manifestations of arsenic toxicity (e.g., inflammation and skin cancer), information on the potential mechanisms through which arsenic may exert its biological effects is also provided. 

The vast majority of information regarding the immunotoxic effects of different chemicals has been derived from laboratory studies of vertebrate responses in which the mechanism of action is evaluated and the subsequent effects on different immune parameters and susceptibility to infection is determined. It is much harder to extrapolate... 

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