Xenobiotics immune system

L-Tyrosine metabohsm and catecholamine biosynthesis occur largely in the brain, central nervous tissue, and endocrine system, which have large pools of L-ascorbic acid (128). Catecholamine, a neurotransmitter, is the precursor in the formation of dopamine, which is converted to noradrenaline and adrenaline. The precise role of ascorbic acid has not been completely understood. Ascorbic acid has important biochemical functions with various hydroxylase enzymes in steroid, dmg, andhpid metabohsm. The cytochrome P-450 oxidase catalyzes the conversion of cholesterol to bUe acids and the detoxification process of aromatic dmgs and other xenobiotics, eg, carcinogens, poUutants, and pesticides, in the body (129). The effects of L-ascorbic acid on histamine metabohsm related to scurvy and anaphylactic shock have been investigated (130). Another ceUular reaction involving ascorbic acid is the conversion of folate to tetrahydrofolate. Ascorbic acid has many biochemical functions which affect the immune system of the body (131). 

One of the more difficult to manage aspects of compound reactivity is the potential for idiosyncratic immunological reactions to covalent protein-compound complexes. Normally the immune system does not respond to xenobiotics of molecular weight less than 1000 Daltons. When, however, a drag is covalently linked to a... 

The majority of early publications that can be reasonably identified as comprising immunotoxicology reported altered resistance to infection in animals exposed to various environmental or industrial chemicals. Authors logically concluded that xenobiotic exposure suppressed immune function since the immune system is ultimately responsible for this resistance to infection. Subsequent studies demonstrated that suppression of various cellular and functional endpoints accompanied or preceded increased sensitivity to infection, and that administration of known immunosuppressants likewise decreased host resistance. The human health implications of these studies, that chemical exposure reduced resistance to infection, drove the initial focus of many immunotoxicologists on functional suppression, and provided the theoretical and practical underpinnings of immunotoxicity testing. 

In recognition of the increased vulnerability of the developing organism, both the U.S. EPA Food Quality Protection Act [77] and the U.S. EPA Safe Drinking Water Act [78] mandate that infants and children warrant special consideration in the risk assessment process. Immune system ontogeny and the sensitivity of the developing immune system to xenobiotics are discussed in detail in chapter 20 of this volume. 

Data suggest that extrahepatic tissue (i.e., the immune system) may also play an important role in the in situ biotransformation of xenobiotics, such as polycyclic aromatic... 

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... 

Immunotoxicology studies the effects of xenobiotics on the immune system an immunotoxic compound is defined as a compound that can alter one or more immune functions, resulting in an adverse effect for the host. In particular, two main immunotoxic effects can be identified ... 

With the exception of whole-animal host resistance assays, the actual testing approach can be described as ex vivo-in vitro in that exposure of the immune system to potential immunotoxicants takes place in vivo, with subsequent immunological evaluation taking place in vitro. Although this approach obviates many uncertainties (effect of xenobiotics on primary or secondary lymphoid tissue, potential requirements for metabolism/bio-transformation, etc.), the use of whole animals presents many secondary issues, such... 

SOT workshop Developing immune system Sensitive target for perturbation by xenobiotics. San Francisco, CA March, 2001... 

As observed in mammalian models, the immune system of fishes is a sensitive target organ system to evaluate toxicity. For a more thorough review of environmental immunotoxicology in fishes, with reference to specific classes of xenobiotics, readers are referred to several reviews that deal with the subject over a span of nearly three decades [45-47, 54-57], While fish in the environment may be exposed to a variety of xenobiotics, the most frequently investigated xenobiotics are the polycyclic aromatic hydrocarbons (PAHs) and halogenated aromatic hydrocarbons (HAHs) due to the presence and activation of the aryl hydrocarbon receptor (AhR) in fish, and heavy metals due to their ubiquitous environmental distribution. 

A thorough review of the immune system is not the intent of this chapter, but a brief description of the important components of the system and their interactions is necessary for an understanding of how xenobiotics can affect immune function. A breakdown at any point in this intricate and dynamic system can lead to immuno-pathology. 

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,... 

Chemical - complex formation. Earlier we discussed the complexation which can occur between the chelating agent EDTA and heavy metals or the sequestration of lipids in cholestyramine resins. The immune system has antibody-antigen complexes formed which can help in the elimination of the antigen (xenobiotic). 

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