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 research, the structural behavior of reinforced concrete columns made of normal and hybrid reactive powder concrete (hybrid by steel and polypropylene fibers) subjected to chloride salts with concentration was 8341.6 mg/l. The study consists of two parts, the first one is experimental study and the second one is theoretical analysis. Three main variables were adopted in the experimental program; concrete type, curing type and loading arrangement. Twenty (120x120x1200) mm columns were cast and tested depending on these variables. The samples were reinforced using two different bars; Ø8 for ties and Ø12 with minimum longitudinal reinforcement (0.01Ag). The specimens were divided into two main groups based o
... Show MoreA series of lanthanide metal (???) complexes have been prepared from the new azo ligand, 3-(1-methyl-2-benzimidazolylazo)-Tyrosine (MBT). The structural feature were confirmed on the basis of their elemental analysis, metal content, molar conductance, magnetic measurement, FTIR, 1 HNMR and UV-Vis spectra studies. The isolated complexes were found to have a mole ratio (1:2) (metal:ligand) stoichiometry with the general formula [Ln(MBT)2]Cl (Ln(???) = La, Ce, Pr, Nd, Sm, Eu and Gd). The chelates were found to have octahedral structures. The FTIR spectra shows that the ligand (MBT) is coordinated to lanthanide ions as a N, N, O-tridentate anion via benzimidazole nitrogen, azo nitrogen and oxygen of hydroxyl after deprotonation. Com
... Show MoreStatistical methods and statistical decisions making were used to arrange and analyze the primary data to get norms which are used with Geographic Information Systems (GIS) and spatial analysis programs to identify the animals production and poultry units in strategic nutrition channels, also the priorities of food insecurity through the local production and import when there is no capacity for production. The poultry production is one of the most important commodities that satisfy human body protein requirements, also the most important criteria to measure the development and prosperity of nations. The poultry fields of Babylon Governorate are located in Abi Ghareg and Al_Kifil centers according to many criteria or factors such as the popu
... Show MoreThis paper aims to study the effect of circular Y-shaped fin arrangement to improve the low thermal response rates of a double-tube heat exchanger containing Paraffin phase change material (PCM). ANSYS software is employed to perform the computational fluid dynamic (CFD) simulations of the heat exchanger, including fluid flow, heat transfer, and the phase change process. The optimum state of the fin configuration is derived through sensitivity analysis by evaluating the geometrical parameters of the Y-shaped fin. For the same height of the fins (10 mm), the solidification time is reduced by almost 22%, and the discharging rate is enhanced by almost 26% using Y-shaped fins compared with the straight fins. The results demonstrate that the sol
... Show MoreTwo field experiments were conducted at two different texture sites. The first site of the fields of AlMed-hateya Agriculture Division / Babil Governorate. The second site of the fields of Al-Nouriah Research Station / Ministry of Agriculture, the factors of the study in the two sites included several factors. The first factor includes two irrigation systems: sprinkler irrigation and surface irrigation. The second factor is the method of cultivation which includes the method of cultivation with basin and furrowing. The third factor is the type of the cultivated crop which includes a local variety (Fajr 3) and a hybrid variety (Drakma). The actual water consumption for the sprinkler irrigation system reached (587.13 and 637.62) mm season-1 f
... Show MoreThe aldol condensation of 2-acetylnaphthalene with 9-anthracene carboxaldehyde afforded α, β-unsaturated keton (1) . New heterocyclic compounds containing: cyclohexenone[2], indazole[3], pyrimidinethion [4], thiazolo fused pyrimidine[5], isoxazoline[6], substituted pyrazoline[7]a-d and pyrimidinone[8] rings system were synthesized from α, β-unsaturated keton[1]. Cyclization of [1] with ethylacetoacetate gave the mentioned heterocycle cyclohexanone [2]. The cyclo condensation of [2] with hydrazine gave the new indazole derivative [3]. furthermore, the reation of [1]with thiourea gives thiopyrmidine derivative [4]. The cyclo condensation of [4] with chloroacetic acid gave the fused rings [5]. Then reacted compound[1] with hydroxy
... Show MoreHeart failure (HF) is characterized by family history and clinical examination combined with diagnostic tools such as electrocardiogram, chest x-ray and an assessment of left ventricular function by echocardiography. An early diagnosis of heart failure is still based on symptoms of dyspnea, fatigue and signs of fluid overload. Serum N-terminal pro-B-type natriuretic peptide (NT-pro BNP) is cardiac biomarker has emerged as potential predictor of heart failure. It is used as a sensitive biomarker in diagnosis and assessment severity of heart failure. This study assed the diagnostic value of (NT-pro BNP), in Iraqi children patients with heart failure and its correlation with LVEF% especially in emergency rooms of hospitals.Ninety (90) consecut
... Show Moreحضر الليكاند (L) 1-فنيل-3-بردين-2-يل مثيل-ثايويوريا من تفاعل 2-أمينو مثيل بردين مع فنيل ايزوثايوسيانيت وبنسبة 1: 1 وشخص الليكاند بواسطة التحليل الدقيق للعناصر (C, H, N), الأشعة تحت الحمراء، الأشعة فوق البنفسجية–المرئية وطيف الرنين النووي المغناطيسي كما حضرت وشخصت معقدات أملاح بعض ايونات العناصر الثنائية التكافؤ (Co, Ni, Cu, Cd and Hg). استخدمت تقنية الأشعة تحت الحمراء، الأشعه فوق البنفسجية-المرئية, التوصيلية الكهربائية و الا
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