Cytokines immune response studies

Several animal model studies have focused on the immune response to infection and also to vaccination. Most studies identify antibody titer, but some also show cytokine production or possible mechanisms of bacterial evasion. A focus on immune response studies will help to further define B. anthracis pathogenesis and provide insight into the design of future vaccines and therapeutics. Most countermeasure studies have been conducted on vaccines, because antibiotic studies have typically been performed in vitro. Primary concerns are the length of required treatment, efficient prophylaxis methods, and less complicated dosing regimens for vaccines. In a theoretical bioterrorist attack scenario, it will be essential to distribute effective treatment and prophylaxis to infected or potentially exposed persons in an expedient manner. 

Muc2 and Muc3, and mucin mRNA are coordinately upregulated in response to T. spiralis infection and may form the basis of an innate mucosal response independent of specific IFN-y, TNF and IL-4 cytokines. Importandy, this study also demonstrated that goblet cell hyperplasia and upregulated mucin secretion are not essential components of the protective immune response to GI helminths. 

The stress-associated shift in Thl/Th2 cytokines observed in human subjects has also been demonstrated in restraint-stressed mice. Associated with the shift towards a Th2 response are a significant decrease in NK cell activity, decreased IFN-y production by Con A-stimulated splenocytes, and a concomitant increase in serum corticosterone levels after 24 hours of restraint.30 These observations are consistent with studies on the effects of restraint stress and the immune response to viral infection. Restraint-stressed mice exhibited a decline in NK cell activity and a decrease in the generation of virus-specific cytotoxic T lymphocytes to HSV-l after primary infection, which resulted in an increase in the replication of the virus at the site of infection.3132... 

Several opiate receptors have been identified on cells of the nervous systems of animals and humans, with mu (p), kappa (k), and gamma (y) subtypes being predominant. These classical opiate receptors are G- protein coupled 7-transmembrane molecules.27 Opiates predominantly affect immune responses directly by ligation of p, k, and y opiate receptors, as well as non-classical opiate-like receptors, on immune cells and indirectly by binding to receptors on CNS cells. Studies conducted in vitro with opiate-treated immune cells demonstrated receptor-mediated reduced phagocytosis, chemotaxis and cytokine and chemokine production. These effects are linked to modulation of host resistance to bacterial, protozoan, viral and fungal infections using animal models, cell lines and primary cells. 

The study of protein function as it applies to covalent and noncovalent molecular changes associated with specific binding is of fundamental interest to those involved with the discovery of therapeutic proteins. Discovering soluble receptors that bind the cytokines that elicit inflammatory immune responses is one of many... 

Importantly, although Th2 cells are responsible for the development of allergic diseases, Thl cells may contribute to chronicity and effector phase in allergic diseases [30-33,38,39]. Distinct Thl and Th2 2 subpopulations of T cells counterregulate each other and play a role in distinct diseases [34,35]. In addition, recent studies have demonstrated that peripheral T-cell tolerance is crucial for a healthy immune response and successful treatment of allergic disorders [40-42]. A further subtype ofT cells, with immunosuppressive function and cytokine profiles distinct from either Thl and Th2 cells, termed regulatory/suppressor T cells (Treg), has been existence in humans has been demonstrated [41,... 

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