Drug hypersensitivity involves the activation of T cells in an HLA allele–restricted manner. Because the majority of individuals who carry HLA risk alleles do not develop hypersensitivity, other parameters must control development of the drug-specific T cell response. Thus, we have used a T cell–priming assay and nitroso sulfamethoxazole (SMX-NO) as a model Ag to investigate the activation of specific TCR Vβ subtypes, the impact of programmed death -1 (PD-1), CTL-associated protein 4 (CTLA4), and T cell Ig and mucin domain protein-3 (TIM-3) coinhibitory signaling on activation of naive and memory T cells, and the ability of regulatory T cells (Tregs) to prevent responses. An expansion of the TCR repertoire was observed for nine Vβ subtypes, whereas spectratyping revealed that SMX-NO–specific T cell responses are controlled by public TCRs present in all individuals alongside private TCR repertoires specific to each individual. We proceeded to evaluate the extent to which the activation of these TCR Vβ–restricted Ag-specific T cell responses is governed by regulatory signals. Blockade of PD-L1/CTLA4 signaling dampened activation of SMX-NO–specific naive and memory T cells, whereas blockade of TIM-3 produced no effect. Programmed death-1, CTLA4, and TIM-3 displayed discrete expression profiles during drug-induced T cell activation, and expression of each receptor was enhanced on dividing T cells. Because these receptors are also expressed on Tregs, Treg-mediated suppression of SMX-NO–induced T cell activation was investigated. Tregs significantly dampened the priming of T cells. In conclusion, our findings demonstrate that distinct TCR Vβ subtypes, dysregulation of coinhibitory signaling pathways, and dysfunctional Tregs may influence predisposition to hypersensitivity.
The present paper is an experimental study to improve the productivity of the conventional solar still. This done by modifying conventional still in a way that the distilled basin is larger than distillation basin, thus providing an increase in the condensation surface and speeding up the condensation process. Moreover, increase in the dimensions of the distilled base helps coupling reflective panels to the distilled base to reflect incident solar radiation to the distillation basin. For this purpose , two solar stills were made, one conventional designand another made according to the proposed design. The two solar stills were tested during the period from February to July 2009 under varying weather conditions of Basra, Iraq (latitude o
... Show MoreThe research aims to indicate the relationship between lean production tools included seven {constant improvement , and Just in time (JIT), and the production smoothing , and quality at the source, and standardized work, Visual management, and activities 5S } and Mass Customization strategy for the model (Pine & Gilomer, 1997) {collaborative, adaptive, cosmetic, transparent}, as well as providing a conceptual framework and applied for variables search to clarify how they will choose a Mass Customization strategy through the lean production tools, , and recognize the reality of the practices of Iraqi industries in such a field. Moreover, aims to highlight the positive aspects that accrue to companies a
... Show MoreObjective: this search aims to test the correlation between job complexity and psychological detachment then stats how the burnout can affect in this relationship and dose the burnout can contribute in development of this relationship. Theoretical framework: the research adopted some questions like how can psychological detachment can make the employee keeping away from work and isolates himself from work environment and how can the job complexity enhance this behavior for employee ,and how can the burnout increase the correlation between job complexity and psychological detachment ?, then trying to extraction some of recommendations may contributes in enhancing practicing and adopting these three variables (job complexity, psych
... Show MoreThe Purpose of this research is analysis and discussion " The Effect of Insurace Company Capital Adequacy in it’s Profitafility: An Empirical Study compared the two insurance (national, Iraqi), for a period of one year (2005) and the year (2014), as it is framed theoretical side for two topics head adequacy money the insurance company, and the profitability of the insurance company, and I've been using the research methodology and analytical, in the analysis and measurement of the capital of the insurance company adequacy, and profitability of the company, as the capital adequacy ratio was measured by dividing the total capital available on the total capital rate risk, after measured and appreciated in two insurance research, while I u
... Show MoreThe glycated haemoglobin A1c(HbA1c) and Fasting blood glucose(FBG) effect on type1 diabetic pateints as a screening tests and as a gold standard for assessing glycemic control in subjects with diabetes were studied . Ninety one blood samples were collected in a peroid between June and the end of November 2012 at AL- Kindy Diabetic Center and Central Child Hospital,48 Females and 43 Males , aging between (11 month- 18 year), are divided into three groups, newly diagnosed , ongoing and healthy control group, with duration of disease between(1 day-3months) and (from birth-8 years) for newly diag
... Show MoreThe research paper aims to highlight the impact of electronic governance in improving the quality of auditing through accounting disclosure and how to make use out of it in resolving many of the problems by economic units in general and in particular the financial problems in particular. It focuses on the most important financial information of the loss of confidence and credibility in the financial information of the economic units, This study has been carried out through the use and application of many of the principles and rules contained in the electronic governance, The most important Which is the accounting disclosure, and hence the dimensions of accounting for electronic governance through the achievement of ac
... Show MoreThe aim of the research is to show the importance of international auditing standards and the effect of this in reducing the incidence of financial irregularities in government service units and how to address them. The research adopted the descriptive, analytical and inductive approaches. In the analytical approach, a questionnaire model was designed and distributed to internal auditors in some of the subordinate government units. For the Ministry of Health, appropriate statistical methods were used that showed the extent of the general understanding of the internal auditor’s relationship with international standards and the impact of this on preserving public money and the role of the internal auditor in detecting financial irregulariti
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