Immune suppression direct effects

No significant harmful health effects to humans or animals are expected from exposure to this pathogen unless the individual has a compromised respiratory system or suppressed immune system. Direct contact with large quantities of B. subtilis spores may cause redness or irritation of the skin. 

Suppressed immune systems were also restored if the treated animal was sufficiently mature to have possessed a developed immune system at the time of its suppression. The immune system of a very young animal with an immature immune system at the time of suppression could only be restored back to the immature state that it had at the time prior to immune suppression. This strongly exhibited the direct time-reversal effect that was occurring. 

IFN-y is produced by THi cells and shifts the response toward a THi phenotype. This is accomplished by activation of NK cells that promotes innate immunity, augmenting specific cytolytic response and induction of macrophages. The induction of cytotoxic immunity can be direct or indirect via suppression of TH2 response. Another direct effect of IFN-y is the differentiation of naive CD4+ lymphocytes toward a THi phenotype. The cytokines present are very important in this differentiation process. Furthermore, induction of IL-12 and suppression of IL-4 by IFN result in differentiation toward a THi phenotype. 

The direct effects opioid and opioidlike peptides exhibit on cells of the immune system is both varied and, in some instances, contradictory, depending on which receptor subtype is being studied. Mu and kappa receptors generally affect immunofunction in a suppressive manner, where delta receptors tend to express immunostimulation [82-85]. However, selected delta antagonists have shown to elicit suppressive effects on B-cell proliferation, NK cell activity, and T-helper cell cytokine production [86]. The alteration of leukocyte function via opioid receptors will be discussed highlighting specific cell subtype immunomodulation. Endorphin shows a inhibitory effect on splenocyte proliferation through central and peripheral autocrine/paracrine pathways [87]. 

Mechanistic information is most relevant for the evaluation and classification of carcinogens. As indicated below, a carcinogenic effect, which is induced by a specific mechanism that does not involve direct genotoxicity, such as hormonal deregulation, immune suppression, cytotoxicity, the detailed search for the underlying... 

So far, none of the immune suppressive drugs showed a significant and stable neuroprotective effects in any of the neuro-degenerative conditions. Moreover, under those conditions when steroids were protective they were suggested to mediate the effect directly rather than via suppressing the immune system. 

One of the critical features of any discussion of the mechanisms of immune suppression must be the appreciation that robust changes in immune function can be mediated by either direct or indirect effects (or both) of a xenobiotic. Direct effects can be associated with distinct types of cells. Perhaps the best examples are cyclosporin A and related immunosuppressive drugs, such as rapamycin and FK-506, which specifically target T cells via an interaction with cytosolic and/or nuclear proteins to disrupt antigen-induced activation of transcription. To date, despite the tremendous evolution of the discipline of immunotoxicology, no other xenobiotic associated... 

A number of chemicals with demonstrable suppression of immune function produce this action via indirect effects. By and large, the approach that has been most frequently used to support an indirect mechanism of action is to show immune suppression after in vivo exposure but no immune suppression after in vitro exposure to relevant concentrations. One of the most often cited mechanisms for an indirect action is centered around the limited metabolic capabilities of immunocompetent cells and tissues. A number of chemicals have caused immune suppression when administered to animals but were essentially devoid of any potency when added directly to suspensions of lymphocytes and macrophages. Many of these chemicals are capable of being metabolized to reactive metabolites, including dime-thylnitrosamine, aflatoxin Bi, and carbon tetrachloride. Interestingly, a similar profile of activity (i.e., suppression after in vivo exposure but no activity after in vitro exposure) has been demonstrated with the potent immunosuppressive drug cyclophosphamide. With the exception of the PAHs, few chemicals have been demonstrated to be metabolized when added directly to immunocompetent cells in culture. A primary role for a reactive intermediate in the immune suppression by dimethylnitrosamine, aflatoxin Bi, carbon tetrachloride, and cyclophosphamide has been confirmed in studies in which these xenobiotics were incubated with suspensions of immunocompetent cells in the presence of metabolic activation systems (MASs). Examples of MASs include primary hepatocytes, liver microsomes, and liver homogenates. In most cases, confirmation of a primary role for a reactive metabolite has been provided by in vivo studies in which the metabolic capability was either enhanced or suppressed by the administration of an enzyme inducer or a metabolic inhibitor, respectively. 

IFN-y also directly modulates the immune response by affecting growth, differentiation and function of both T- and B-lymphocytes. These effects are quite complex and are often influenced by additional cytokines. IFN-y acts as a growth factor in an autocrine manner for some T cell sub-populations, and it is capable of suppressing growth of other T cell types. It appears to have an inhibitory effect on development of immature B-lymphocyte populations, but it may support mature B cell survival. It can both up-regulate and down-regulate antibody production under various circumstances. 

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