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.
Abstract
This study aims at identifying the impact of the application of IFRS 15 "Revenue from contracts with customers on the quality of financial reporting, through application to faculty members in the accounting departments of Iraqi universities and auditors. The problem of the study was the multiplicity of accounting rules and standards Which deals with the issues of revenue recognition , as well as the lack of consistency of most of them with the common framework of financial accounting, which results in low quality of financial reporting in the current financial statements, where the formulation of one hypothesis was the lack of relationship of significant significance The application of IFRS 15 "Recognition of rev
... Show MoreThe performance of a diesel engine was tested with diesel oil contaminated with glycol at the engineering workshop/Department of Agricultural Machines and Equipment / College of the Agricultural Engineering Sciences at the University of Baghdad. To investigate the impact of different concentrations of glycol on the performance of a diesel engine, an experimental water-cooled four-stroke motor was utilized, with oil containing 0, 100, and 200 parts per million (ppm). Specific fuel consumption, thermal efficiency, friction power, and exhaust gas temperature were examined as performance indicators. To compare the significance of the treatments, the study employed a full randomization des
The performance of a diesel engine was tested with diesel oil contaminated with glycol at the engineering workshop/Department of Agricultural Machines and Equipment / College of the Agricultural Engineering Sciences at the University of Baghdad. To investigate the impact of different concentrations of glycol on the performance of a diesel engine, an experimental water-cooled four-stroke motor was utilized, with oil containing 0, 100, and 200 parts per million (ppm). Specific fuel consumption, thermal efficiency, friction power, and exhaust gas temperature were examined as performance indicators. To compare the significance of the treatments, the study employed a full randomization des
The performance of a diesel engine was tested with diesel oil contaminated with glycol at the engineering workshop/Department of Agricultural Machines and Equipment / College of the Agricultural Engineering Sciences at the University of Baghdad. To investigate the impact of different concentrations of glycol on the performance of a diesel engine, an experimental water-cooled four-stroke motor was utilized, with oil containing 0, 100, and 200 parts per million (ppm). Specific fuel consumption, thermal efficiency, friction power, and exhaust gas temperature were examined as performance indicators. To compare the significance of the treatments, the study employed a full randomization design (CRD), with three replicates for each treatment at th
... Show MoreThe current research aims to identify the multiple intelligences in the fourth students’ acquisition of the literary processes of Arabic grammar and to identify the differences in multiple intelligence according to gender (males - females). The study was determined for students of the fourth literary preparatory Al-Hakim Preparatory (for males) and Rabat Preparatory (for females) of the Second Karkh Education Directorate, topics from the Arabic grammar subject (past tense, present tense, imperative, subject, and object) for the first semester of the academic year 2019-2020. The results showed that there were no statistically significant differences at the significance level (0.05) between the average scores of the students who were tau
... Show MoreThe antibacterial effect of (Eruca sativa) extract was evaluated by an in vitro study testing the growth of various Gram-Positive and Gram-Negative bacteria . The bactericidal activity of this extract was analyzed by serial dilution in tubes. This study,found that Gram-Negative and Gram-Positive bacteria susceptible to very low eruca concentrations. On the other hand, Gram-positive bacteria were more susceptible than Gram-negative bacteria, the minimal bactericidal concentration of Gram-positive bacteria was 5 mg ml-1 but minimal bactericidal concentration of Gram-negative bacteria was 10 mg ml-1 that mean duble inhibation concentration of Gram-positive bacteria . this study suggest that Eruca sativa leaves have inhibation effect on Gra
... Show MoreThis study produces an image of theoretical and experimental case of high loading stumbling condition for hip prosthesis. Model had been studied namely Charnley. This model was modeled with finite element method by using ANSYS software, the effect of changing the design parameters (head diameter, neck length, neck ratio, stem length) on Charnley design, for stumbling case as impact load where the load reach to (8.7* body weight) for impact duration of 0.005sec.An experimental rig had been constructed to test the hip model, this rig consist of a wood box with a smooth sliding shaft where a load of 1 pound is dropped from three heights.
The strain produced by this impact is measured by using rosette strain gauge connected to Wheatstone
