Immune response, agents affecting immunization

This, in turn, has led to investigation of OP-mediated suppression of the hypothalamic-pituitary-adrenal axis (Pena-Philippides et al., 2007). However, anti-ChEs were also found to initiate acute immune responses. For example, the nerve agent soman induces an increase in the pro-inflammatory cytokine TNFa, IL-lp, and fL-6 in rats, including in the brain, where IL-lp is thought to contribute to irreversible brain damage (Banks and Lein, 2012). This bidirectional impairment of immune functions may reflect systemic responses that affect more than the cholinergic system alone. 

Microbial risks are mostly due to single exposures (except for microbial toxins) chemical risks are affected by chronic duration of exposure. Responses to infective pathogens are probably more variable as compared to chemical agents due to different subpopulations and depending on immune status. 

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. 

Because of the autoimmune basis of rheumatoid arthritis, various other drugs that affect the immune response are used on a limited basis. For instance, cyclosporine (Sandimmune), an immunosuppressant agent that is used to prevent rejection of organ transplants (see Chapter 37), is sometimes used to treat... 

The interferons are a family of proteins secreted by animal cells in response to viral and parasitic infections, and are part of the host s defence mechanism. They display multiple activities, affecting the functioning of the immune system, cell proliferation, and cell differentiation, primarily by inducing the synthesis of other proteins. Accordingly, they have potential as antiviral, antiprotozoal, immunomodulatory, and cell growth regulatory agents. 

Data are available for acute and intermediate inhalation exposures that resulted in death of animals. For the most part, these exposures also affected the respiratory tract and the immune response to bacterial agents. An intermediate inhalation exposure study of rats prior to mating and during pregnancy did not result in fetotoxic or teratogenic effects. Limited information is available regarding chronic inhalation exposure. 

Benzene also affects functional immune responses, as indicated by decreased resistance to infectious agents. Pre-exposure to benzene at >30 ppm for 5-12 days increased the bacterial counts in mice on day 4 of infection with Listeria monocytogenes (Rosenthal and Snyder 1985). Recovery of the immune system was noted on day 7. The effects did not occur at 10 ppm. In addition, a concentration-dependent statistically significant depression was noted in T- and B-lymphocyte populations from day 1 through day 7 at 30 ppm and above. B-cells were more sensitive to benzene than were T-cells on a percentage-of-control basis. This indicates a benzene-induced delay in immune response to L. monocytogenes. Concentrations of 200 or 400 ppm for 4-5 weeks (5 days per week) suppressed the primary antibody response to tetanus toxin in mice, but there was no effect at 50 ppm (Stoner et al. 1981). In another intermediate-duration exposure study, no changes were noted in the numbers of splenic B-cells, T-cells, or... 

The effects of marijuana on immune function have been reviewed (122). The studies suggest that marijuana affects immune cell function of T and B lymphocytes, natural killer cells, and macrophages. In addition, cannabis appears to modulate host resistance, especially the secondary immune response to various infectious agents, both viral and bacterial. Lastly, marijuana may also affect the cytokine network, influencing the production and function of acute-phase and immune cytokines and modulating network cells, such as macrophages and T helper cells. Under some conditions, marijuana may be immunomodulatory and promote disease. 

With the discovery and development of cyclosporine, a new era in immunopharmacology was born. Cyclosporine was the first agent to affect a specific cell line of the body s immune defenses. It is suppressive mainly to T cells, in condast to the cytotoxic agents, which affect all cell lines at the same time. Cyclosporine is the forerunner of a group of immunosuppressants that are acdve against specific components of the immune response. 

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