Toxic Effects on the Immune System

The immune system of the body serves a number of valuable functions, mostly related to defense against foreign agents. Included among immune system functions are the following (1) defense against viral, bacterial, and protozoal infectious agents (2) destruction and nentralization of neoplastic (cancerous) cells and (3) resistance to xenobiotic toxicants. 

Adverse effects on the immune system are among the more important aspects of toxicological chemistry. Such effects may be divided into two major categories. One of these is immunosuppression, which impairs the immune system s ability to resist the effects of toxicants, to fight disease-causing agents, and to impede the development of cancerons cells, snch as those responsible for leukemia or lymphoma. 

As those who suffer from allergies well know, overstimulation of the immune system can cause significant ill effects. Known as allergy or hypersensitivity, the self-destructive overstimulation of the immune system can result from xenobiotic substance exposure. Some metals including 

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Gopinath, C. (1996) Pathology of toxic effects on the immune system. Inflammation Research, 45, S74-S78. 

Immunological Effects. No studies were located that investigated toxic effects on the immune system in humans or animals exposed to silver, or that indicate that immune-related disease can be affected by silver exposure. Silver has been observed to elicit a mild allergic response (contact dermatitis) in humans following dermal exposure to various silver compounds. 

There should be an extension of research into the analysis of human body fluids, e.g. blood, urine, milk by way of adducts specific to the perceived most harmful mycotoxins. There should also be continued examination of novel ways of determining toxic effects on the immune system. The use of human cell lines for toxicity studies should be further developed especially using cells that have been transfected with human cytochromes. 

The highest NOAEL values for immunological effects in each species and duration category are recorded in Table 2-1 and plotted in Figure 2-1. The existing data suggest that 1.1.1-trichloroethane may not produce toxic effects on the immune system, but sensitive immunological end points have not been examined in humans or animals. 

Immunologic Toxicity—The occurrence of adverse effects on the immune system that may result from exposure to environmental agents such as chemicals. 

Apart from the wide range of neurotoxic and behavioral effects caused by OPs, many of which can be related to inhibition of AChE, other symptoms of toxicity have been reported. These include effects on the immune system of rodents (Galloway and Handy 2003), and effects on fish reproduction (Cook et al. 2005 Sebire et al. 2008). In these examples, the site of action of the chemicals is not identified. Indirect effects on the immune system or on reproduction following initial interaction with AChE of the nervous system cannot be ruled out. It is also possible that OPs act directly on the endocrine system or the reproductive system, and phosphorylate other targets in these locations (Galloway and Handy 2003). 

Immunotoxicity. No information was found regarding immunotoxicity in humans from inhalation, oral, or dermal exposures to fuel oils. Only two animal studies were identified that tested immunological effects, both using mice. These studies identified cellular effects in the bone marrow, lymph nodes, and/or thymus and decreases in the relative weights of the lymph nodes and thymus from acute dermal exposures to kerosene (Upreti et al. 1989) and chronic dermal exposures to JP-5 and marine diesel fuel (NTP/NIH 1986). However, the toxicological significance of these effects on the immune system cannot be determined from these data. Additional data are needed to identify the toxic potential of fuel oils on the immune system by all routes of exposure and in different animal systems. 

The thymus, spleen, and lymphoid tissues aU have immunological function and changes to them can be indicative of adverse effects on the immune system. Indications of immunotoxicity from standard repeated dose toxicity smdies include one or more of the following signs ... 

The various organs of the immune system such as spleen, lymph nodes, thymus and bone marrow containing the cells involved in the various immune responses offer the possibility to harvest these cells and perform in vitro assays for evaluation of effects on the immune system. When part of an in vivo animal study this may indicate a direct toxic effect of pharmaceuticals, that is, immunosuppression (Table 18.2). So, it is feasible to obtain cell suspensions for further evaluation such as determination of cellular subsets of T and B leukocytes by fluorescent activated cell sorter analysis (FACS analysis), and determination of natural killer (NK) cell activity of the spleen cell population. An advantage of this approach is that it may lead to identification of a biomarker to be used in clinical studies. In addition, in vitro stimulation of spleen cells with mitogens activating specific subsets may indicate potential effects on the functionality of splenic cell populations. Concanavalin A (Con A) and phytohemagglutinin (PHA) activate Tcells, while lipopolysaccharide (LPS) activates primarily B cell populations. Blood is collected for total white blood cell (WBC) determination and blood cell differential count. In addition, serum can be obtained for determination of serum immunoglobulins. 

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