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.
Current research targeted: Recognizing the impact of the differentiated education strategy on the achievement of the students of the Institute of Fine Arts / Diyala, for the academic year (2018-2019).
The researcher used the experimental approach designed by two groups (control - experimental) and with a post-test to achieve the goal of the research, and the research sample was chosen from students of the fourth stage for the academic year (2018-2019).
The sample was distributed randomly into two groups, the first experimental consisting of (30) students who studied using the differentiated education strategy, and the second control group consisting of (30) students who studied using the traditional method.
The researcher pre
The aim of this research is to measure and analyze the gap between the actual reality and the requirements of the environmental management system in the middle refineries company/refinery cycle according to ISO14001: 2015, as well as to measure the availability of a clean production strategy and test the relationship and impact between the availability of the requirements of the standard and a clean production strategy for the actual reality in the company.
The research problem was determined by the extent to which the requirements of the environmental management system are applied according to ISO14001: 2015 in the middle refineries company? To what extent are the required clean production strategies ava
... Show MorePlant tissue culture techniques were exploited for the micropropigation of Lisianthus (Eustoma grandiflora). Different concentrations of Benzyl adenine (BA), 6- Furfural amino purine (Kinetin), Indol butyric acid (IBA), were investigated in their effects at different micropropagation stages. Three explants (apical shoots, internodes, leaf discs) were used in this study. The effect of the interaction between BA and IBA on shoot multiplication was investigated in increasing the number of shoots on explants. Rooting was also studied after inclusion of IBA and NAA to Murashige and Skoog, 1962 culture medium (MS). During acclimatization stage, different ratios of river sand and peat moss as agricultural media were tested and plantlets survival w
... Show MoreBackground: The healing period for bone–implant contact takes 3–6 months or even longer. Application of Escherichia coli-derived recombinant human bone morphogenetic protein-2 (ErhBMP-2) to implant surfaces has been of great interest on osseointegration due to its osteoinductive potential. The objective of this study was to evaluate the effect of ErhBMP-2 on implant stability. Materials and methods: A total of 48 dental implants were inserted in 15 patients. Twenty four implants coated with 0.5 mg/ml ErhBMP-2 (study group). The other 24 implants were uncoated (control group). Each patient was received at least two dental implants at the same session. Both groups were followed with repeated implant stability measurements by me
... Show MoreThe performance and lifetime of the flexible asphalt pavement are mainly dependent on the interfacial bond strength between layer courses. To enhance the bond between layers, adhesive materials, such as tack coats, are used. The tack coat itself is a bituminous material, which is applied on an existing relatively non-absorbent surface to ensure a strong bond between the old and newly paved layer. The primary objective of this study was to evaluate the effects of various types of tack coat materials on interlayer bond strength and to determine the optimal application rate for each type. The tack coat types used in this paper were RC-70, RC-250, and CSS-1h. Both laboratory-prepared and field-constructed hot mix asphalt concrete pavements usin
... Show Moreيشهد العالم تقدما في كافة مجالات الحياة المختلفة وتزداد الحياة صعوبة يوما بعد يوم, ويزداد البحث في كافة المجالات التي تعمل على خدمة الإنسان ولقد طال هذا التقدم النشاط الرياضي ,فقد يكون لتطور التدريب الرياضي وتنوع أساليبه الدور الكبير في تحقيق اللياقة البدنية التي تعد إحدى أهم الأهداف التي يرمي إليها الدرس في كلية التربية الرياضية . واللياقة البدنية تستمد أهميتها من كونها إحدى مكونات اللياقة الشاملة التي بدو
... Show MoreBackground/Objectives: Nonsurgical periodontal treatment (NSPT) is the gold-standard technique for treating periodontitis. However, an individual’s susceptibility or the inadequate removal of subgingival biofilms could lead to unfavorable responses to NSPT. This study aimed to assess the potential of salivary and microbiological biomarkers in predicting the site-specific and whole-mouth outcomes of NSPT. Methods: A total of 68 periodontitis patients exhibiting 1111 periodontal pockets 4 to 6 mm in depth completed the active phase of periodontal treatment. Clinical periodontal parameters, saliva, and subgingival biofilm samples were collected from each patient at baseline and three months after NSPT. A quantitative PCR assay was us
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