Immune function, system, response

The central aspect of clinical testing in infants should include the evaluation of a diverse spectrum of immune functions in response to an added substance. To develop the appropriate tests for assessing the safety of the immunological responses to new substances, it is useful to first identify the target tissues affected by the interaction of ingested substances with the host immune system (Table 6-7). 

Among vertebrate species, the neuro-endocrine-immime system is responsible for many complex, inter-related physiological processes including neuronal, homeostatic, reproductive and immune functions. There are four main types of hormone polypeptides, eicosanoids, steroids and thyroid hormones. Reflecting the inter-dependency of the neiiro-endocrine and immune systems, hormones, neuropeptides and other neiirotransmitters are known to be produced by some immune cells and play a role in the regulation of the immune system, while endocrine and nervous tissues express receptors for many substances produced by the immune system. The major focus of interest in endocrine disruption has... 

The endogenous opioids are another family of peptides involved in different physiological processes including pain regulation, respiratory control, stress responses, appetite, thermoregulation, and humoral and cellular immune function (Bodnar RJ., 2008). Opioids act through their receptors, which are also members of the GPCR family, and are expressed in the central and peripheral nervous system as well as on cells of the immune system (Henriksen and Willoch 2008 Hauser... 

A wide diversity of herbal remedies have purported abilities to stimulate defense functions. Complexes of carbohydrate and lignin, which are present in some herbs, modulate enteric immune functions (Kiyohara et al, 2000), and the changes in cytokine secretion (Matsumoto and Yamada, 2000) can trigger systemic responses. The polysaccharides present in other herbal medicines augment production of immunoglobulin (Ig) A by the Peyer s patches in the small intestine (Sakushima et al, 1997 Yu et al, 1998). The responses of the enteric immune system to lectins are variable (Pusztai 1993), and can elicit systemic responses (Lavelle et al, 2000). Other phytochemicals provide protection by inducing detoxification pathways in mucosal cells (Williamson et al, 1998). 

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. 

The impacts of contaminants on the structure of the immune system can be assessed by examining white blood cell (WBC) numbers and the mass and cellularity of immune organs, although these indicators are usually not as sensitive as measures of immune function. Avian immunotoxicity studies frequently assess total and (or) differential WBC counts [79], and immunosuppression can be indicated by reduced numbers of WBCs or elevated WBC numbers caused by recurrent infections. An elevated heterophil to lymphocyte ratio can indicate altered immune status in response to corticosteroid stress hormones or other factors [78,7 9], Exposure to lead shot or lead acetate has been shown to alter total and (or) differential WBC numbers in Japanese quail (Coturnix coturnix) and mallards [81-83], In western grebes (Aechmophorus occidentalis) from California, concentrations of mercury in the kidney were positively correlated with heterophil... 

However, selective HR2 antagonists have attracted interest because of their potential immune response-modifying activify [88]. Mosf data suggest that cimetidine has a stimulatory effect on the immune system, possibly by blocking the receptors on subsets of T lymphocytes and inhibiting HR2-induced immunosuppression. Cimetidine has also been used successfully to restore immune functions in patients with malignant disorders, hypogammaglobulinemia and AIDS-related complexes. 

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