Immune immunocompetent cells

The major mode of action of such products appears to be depot formation at the site of injection. The antigen is only slowly released from the gel, ensuring its sustained exposure to immune surveillance. The aluminium compounds are also capable of activating complement. This can lead to a local inflammatory response, with consequent attraction of immunocompetent cells to the site of action. 

Both aspects, the lack of an IgM-to-IgG switch and the slow normalization of intrathecal antibody synthesis, could be consequences of the same problem the handicapped regulation of the intrathecal immune response. Given the barrier-dependent low immunoglobulin concentration in CNS and the local (perivascular) invasion of relatively few immunocompetent cells, we might calculate a 10 lower probability for the encounter of cells and antibodies compared to blood. Irrespective... 

The immune system in the majority of patients was compromised by the initial condition (Table 31.2), as was evident by snppression of immunocompetent cells though it was not reflected in prodnction of immunoglobulins IgA and IgM. 

The immune system of patients with postoperative multiple organ failure is compromised, which is confirmed by the decrease of immunocompetent cells but not immunoglobulins IgA and IgM. Nonspecific immunity of these patients is also depressed. However, after extracorporeal blood purification had been performed, immune system stimulation was observed, which was higher than hemosorption specific indicators of cellular and humoral immunity. 

A substantial number of clinicians consider the removal of products of abnormal blood metabolism by hemosorption as a major factor of its clinical outcome. However the effect of direct detoxification on pathological process could be compromised because not only toxic substances but some of the circulating immune complexes, immunocompetent cells and biologically active substances are also removed from the blood. 

Such events show how the immune, endocrine and central nervous systems are integrated in their responses to any form of stress. It is well established that physical or psychosocial stress causes increased secretions of prolactin, growth hormones, thyroid, and gonadal hormones, in addition to ACTH. Endogenous opioids are secreted under such conditions and function as immunomodulators, while also elevating the pain threshold. Receptors for such hormones exist on immunocompetent cells, along with receptors for catecholamines, serotonin and acetylcholine. 

The following protocols can be used for the isolation and structural characterization of any natural bioactive peptides from the immune system of invertebrates. The different procedures that will be detailed below refer to the identification and primary structure determination of the Drosophila immune-induced peptides (19,20,23,27,30) and of bioactive peptides from the immune system of other Diptera (17,21,24,31). These approaches were also successfully used for the discovery of bioactive peptides from crustaceans, arachnids, and mollusks. These methods should be considered as a guideline and not as the exact procedure to follow (see Note 3). The suggested procedures will be reported following the normal order of execution, (1) induction of the immune response by an experimental infection, (2) collection of the immunocompetent cells (hemocytes), tissues (epithelia, trachea, salivary glands, etc.)... 

Immunogenicity The ability of an immunogen to elicit an immune response. Immunogenicity depends upon foreignness to the host, the size of the immunogen, the complexity of its molecular structure, the length of time it remains in the host and its ability to reach certain immunocompetent cells in order to generate immunity. 

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. 

The complexity of the immune system renders it readily attacked by many chemicals. Such attack may result, for example, in organ damage in the thymus, bone, and lymph nodes as well as in cellular pathology in immunocompetent cells. More than 350 different compounds have been identified as immunotoxinsJ5 6 Table 25.1 contains a representative list of these. This list includes heavy metals, chlorinated and organophosphorus pesticides, aromatic hydrocarbons, polynuclear aromatic hydrocarbons, organic solvents, and many widely used chemicals. Many lipophilic and hydrophilic chemicals are immunotoxins and the immunotoxicity of these compounds is manifest via multiple mechanisms. 

Inhibition of the normal immune response results from a gradual destruction of lymphoid tissue, followed by a decline in antibody production and a decrease in the numbers of eosinophils, basophils, and lymphocytes. The reduction in T-lymphocyte counts by glucocorticoids can occur acutely as a result of the redistribution of these cells from the intravascular space to the spleen, lymph nodes, and bone marrow. Thus an increase in the neutrophil count is commonly observed after glucocorticoid administration. The major suppressive effects of glucocorticoids on the inflamniatory response and the immune system appear to be through the modulation of cytokine production via an inhibition of nuclear factor kappa B (NF-kB) expression and nuclear translocation. Cytoldnes released from immunocompetent cells mediate both the acute and chronic phases of inflammation and participate in the control of the immune response (see Chapter 22). 

Some adjuvants (endotoxin and poly(A.U)) increase synthesis of proteins. Other adjuvants stimulate different cellular compartments of the immune system (i) mycobacteria, retinol, and poly(A.U) expand T-cell populations (ii) endotoxin and Bordetella pertussis stimulate B cells and, (iii) many adjuvants of bacterial origin mobilize macrophages. Complete Freund s adjuvant causes local formation of granulomas which are rich in macrophages and immunocompetent cells. 

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