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.
In this work an approach has been developed to investigate the influence of surface roughness on thermohydrodynamic performance in aligned and misaligned journal bearings by considering an average flow model and deriving the shear flow factor for various roughness configurations, similar to the pressure flow factor. An average Reynolds equation for rough surfaces is defined in term of pressure and shear flow factors, which can be obtained by numerical flow simulation, though the use of measured or numerically generated rough surfaces. Reynolds, heat conduction and energy equations are solved simultaneously by using a suitable numerical technique (Finite Difference Method) to obtain the pressure and temperature di
... Show MoreWriting in English language demands both mental skills and a suitable level of language proficiency. Some studies showed that writing anxiety has an impact on the acquisition of language learning. This study; however, teaches the cognitive strategies (PLAY & WRITE) as a writing strategy, so as to decrease students’ use of it when experiencing writing anxiety at the academic writing level. The sample has been (100) second-stage Department of English learners at the College of Education (Ibn –Rushd), in the University of Baghdad-Iraq. They have been randomly selected and divided into experimental and control groups; (50) students in each group. To achieve the objective of the study, SLWAI questionnaire has been distributed to the e
... Show MoreBackground: Treatment of malocclusions using removable orthodontic appliances may prepare new stagnant areas susceptible for colonization and retention of Candida species, therefore; the aim of this study was to investigate the effect of upper removable orthodontic appliances on the mucosal Candidal count in group of apparently healthy orthodontic patients. Materials and Methods: Patients enrolled in this study were children aged 8-12 years having upper removable orthodontic appliances. Candidal counts at six mucosal sites were estimated using Imprint Culture method before, 14 and 28 days during orthodontic therapy. Results: Whole mouth and individual mucosal sites for Candidal counts increase significantly during treatment with upper remov
... Show MoreThe speed of skills has become linked to modern methods of individual and group play, and each of them has begun to serve the other tactically. Through the follow-up of the researchers, they noticed that there is a significant weakness in the speed of performance and slowness in mental preparation, which plays a major role in understanding mental readiness, which is linked to the speed of making decisions during the game, as well as the weakness of the physical speed of the female players, which in turn has an impact on the skill performance of the players of the Iraqi clubs, which are the main supporter of the national team. The study aimed to identify the effect of interactive speed training on the performance of some skills among
... Show MoreWhile many educators are highly focused on state test, it is important to consider that
over the course of a year, instructors can build in many opportunities to assess how learners
are learning. Therefore, assessment techniques are considered a good method to get benefit
for both instructors and learners in the process of teaching and learning. The sample consists
of 27 learners who participated in TOEFL training course in the Development and Continuous
Education Centre. Validity and reliability were verified.
To fulfill the aims and verify the hypothesis which reads as follows” It is hypothesized
that the TOEFL learners' scores will not be increased after TOEFL course training.” T-test
for two dependent samp
The 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 MoreA new pavement technology has been developed in Highway engineering: asphalt pavement production is less susceptible to oxidation and the consequent damages. The warm mix asphalt (WMA) is produced at a temperature of about (10-40) oC lower than the hot asphalt paving. This is done using one of the methods of producing a WMA. Although WMA's performance is rather good, according to previous studies, as it is less susceptible to oxidation, it is possible to modify some of its properties using different materials, including polymers. Waste tires of vehicles are one of the types of polymers because of their flexible properties. The production of HMA, WMA, and WMA modified with proportions of (1, 1.5, and 2%) of rub
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