Immune activity

The clinical measurement of prostaglandin D2, produced in the body by activation of immune-active cells, required the synthesis of the major urinary metabolite. A synthesis was developed starting with the standard intermediate for PG synthesis. 

Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown aetiology with some autoimmune features. Current thinking favours the hypothesis that interplay between genetic factors, sex hormones, and possibly an infectious agent or another immune activating agent initiates an autoimmune pathogenic mechanism that culminates in a disease with inflammatory and destructive features. 

Male mice exposed to 7.3 mg/kg/day for 13 weeks had significantly decreased spleen weights and decreased neutrophil counts (Hoechst 1984b), indicating that immune activity in mice may also be affected. An intermediate-duration oral MRL of 0.005 mg/kg/day was derived based on the NOAEL of 0.45 mg/kg/day for immunotoxicity identified in the Banerjee and Hussain (1986) study. In support of these positive findings, Khurana et al. (1998) observed decreased macrophage functionality, in the absence of any other apparent toxicological effects, in 1-day-old broiler chicks fed 30 ppm endosulfan in the diet for 4 or 8 weeks. 

Achim CL, Heyes MP, Wiley CA (1993) Quantitation of human immunodeficiency virus, immune activation factors, and quinolinic acid in AIDS brains. J Chn Invest 91(6) 2769-2775... 

Sevigny JJ, Albert SM, McDermott MP, McArthur JC, Sacktor N, Conant K, Schifitto G, Seines OA, Stem Y, McClernon DR, Palumbo D, Kieburtz K, Riggs G, Cohen B, Epstein LG, Marder K (2004) Evaluation of HIV RNA and markers of immune activation as predictors of HIV-associated dementia. Neurology 63(ll) 2084-2090... 

HIV produces profound CD4 depletion, possibly through initial massive depletion of gut-associated memory T-cells, followed by chronic immune activation, leading to fatigue of homeostatic T-cell responses and progressive immunodeficiency (McArthur et al. 2005). 

Arthur, M.J.P., Kowalski-Saunders, P. and Wright, R. (1986b). In nvo and in vitro effects of endotoxin on immune-activated hepatic macrophages. Hepatology 6, 800A. 

As with UC, the immune activation seen in CD involves the release of many proinflammatory cytokines. Cytokines thought to play major roles in CD are derived from T-helper type 1 cells and include interferon-y, TNF-a, and IL-1, IL-6, and IL-12. TNF-a is a major contributor to the inflammatory process seen in CD. Its physiologic effects include activation of macrophages, procoagulant effects in the vascular endothelium, and increases in production of matrix metallo-proteinases in mucosal cells.9,15 Excessive production of both... 

It has been postulated that Chlamydia may produce a heat shock protein that causes tissue damage through a delayed hypersensitivity reaction. C. trachomatis may also possess DNA evidence of toxin-like genes that code for high-molecular-weight proteins with structures similar to Clostridium difficile cytotoxins, enabling inhibition of immune activation. This may explain the observation of a chronic C. trachomatis infection in subclinical PID. 

Geng YJ, Holm J, Nygren S, Bruzelius M, Stemme S, Hansson GK. Expression of the macrophage scavenger receptor in atheroma—relationship to immune activation and the T-cell cytokine interferon-gamma. Arterioscler Thromb Vase Biol 1995 15(11) 1995-2002. 

Alonso-Alvarez, C., Bertrand, S., Devevey, G., Gaillard, M., Prost, J., Faivre, B., and Sorci, G. 2004. An experimental test of the dose-dependent effect of carotenoids and immune activation on sexual signals and antioxidant activity. Am. Nat. 164 651-659. 

Hackett, C.J., Innate immune activation as a broad-spectrum biodefense strategy prospects and research challenges, J. Allergy Clin. Immunol., 112, 686, 2003. 

Altered Catecholamine Availability with Immune Activation... 

Non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, were utilized primarily to protect from inflammation. Other biological effects were also found gradually, for example, induction of apoptosis [94, 95], stimulation of immune activity... 

Fig.1. Mast cells bridge innate and adaptive immunity. Activation of mast cells by TLR ligands induces a fast local inflammatory response. Mast cell-derived mediators also promote the migration of antigen-laden LCsfrom the skin to the regional LNs, where a specific adaptive immune response is induced.

In summary, regulation through tryptophan catabolism appears to be an essential component of host responses to fungi such that its manipulation may allow fungi to either evade or promote immune activation. 

Successful vaccines have several important properties such as safety, effectiveness, low cost per dose, and ease of preparation. Vaccines, whether peptide, protein, or DNA, have limited potency without codelivery with an adjuvant and/or a specialized delivery system (11). There is currently a lack of safe, nontoxic, effective. Food and Drug Administration (FDA)-approved vaccine adjuvants capable of stimulating cellular (Thl) immunity (12). Most potent immune activators are also toxic at relatively low doses and cannot, therefore, be successfully used as adjuvants (12). 

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