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.
This research shows the experimental results of the bending moment in a flexible and rigid raft foundation rested on dense sandy soil with different embedded depth throughout 24 tests. A physical model of dimensions (200mm*200mm) and (320) mm in height was constructed with raft foundation of (10) mm thickness for flexible raft and (23) mm for rigid raft made of reinforced concrete. To imitate the seismic excitation shaking table skill was applied, the shaker was adjusted to three frequencies equal to (1Hz,2Hz, and 3Hz) and displacement magnitude of (13) mm, the foundation was located at four different embedment depths (0,0.25B = 50mm,0.5B = 100mm, and B = 200mm), where B is the raft width. Generally, the maximum bending
... Show MoreThis in order to test the effect of food on growth and fecundity, two kinds of food have been used the algae Scendesmus quadricaudae and fresh water shrimp powder. For two generations, growth and productivity have been followed up. The fresh water shrimp has been noticed as a food better than algae, because it caused recording, for the two generation higher length rate for the weeks of experiment. The individuals length rate at the end of the forth week reached 9.35 and 9.48 mm for the first generation and second generation respectively. The average length weekly increase rate for the first and second generations individuals feeding on dried shrimp was higher through the first and second week compared to what was recorded when feeding alga
... Show MoreThe present study was carried out to assay the bioaccumulation of ammonia ,nitrite ,nitrate in fresh water and the concentration of heavy metals (Lead, Cupper, Cadmium, Manganes and Zinc) in water and tissues of Tilapia niloticus selected from El-marryotia canal (one of the river Nile ramification in Al-Giza city) in Egypt, samples were collected during the period of July to October 2011 to determine water safety for human consumption and the hazardous effect of these metals on the histopathology of selected tissues and organs of fish. Two samples were collected from two locations of canal, pH of water samples were measured and the concentration of ammonia, nitrate
... Show MoreShatt al-Arab is the only navigational artery in Iraq, extending from the city of Qurna to its mouth in the Arabian Gulf at the city of Al-Fao within the governorate of Basrah for a length of approximately 204 km. Its width ranges from 400 m to 2000 m, and its depth ranges from 8 m to 20 m. The southern part of it, 93 km long from Umm al-Rassas Island to Ras al-Bisha, represents the international border between Iraq and Iran, where the Thalweg line represents the border between the two countries, which is the deepest point in the riverbed (according to the 1975 Algiers Agreement). The western bank (the Iraqi side) within the common border of Shatt al-Arab is subject to continuous erosion, which leads to the shifting of t
... Show MoreThe aim of the present work to study the effect of changing velocity (Reynold's number) on oxygen cathodic polarization using brass rotating cylinder electrode in 0.1, 0.3 and 0.5N NaCl solutions (PH = 7) at temperatures 40, 50 and 600 C. Cathodic polarization experiments were conducted as a function of electrode rotational speed and concentration.
Thiamethoxam is a synthetic organic insecticide belong to The most significant new class of pesticides created in the last thirty years is neonicotinoids. This study's objective was to determine the effect of thiamethoxam, lambda cyhalothrin and their combination on biochemical parameters, the levels of free radicals and enzymes activities liver of male.Forty Rats ( 150-170 g ) were used. animals Were separated into four groups, each with ten rats.The Gp1 was used as control, the Gp2 was used to study the effect of thiamethoxam for 3weeks, the Gp3 was employed to examine the impact of lambda cyhalothrin for 3 weeks and the Gp4 was used to research the impact of thiamethoxam and lambda cyhalothrin for 3 weeks. thiamethoxam and/or lambda cyha
... Show MoreBackground: Moral distress, as one of the most important issues in the nursing profession, can negatively affect the healthcare system Objectives: To examine the effect of moral distress on decision making. Methodology: A descriptive cross-sectional study a non-probability sampling method was used and a total sample collected was (126) ICU nurses Result: Moral distress among ICUs nurses were moderate and decision making was good Conclusion: Although nurses in ICUs perceive good decision making but suffered from moderate MD which affected their decision making. MD is still an important issue that nurses may face in ICUs Conclusion: Although nurses in ICUs perceive good decision making but suffered from moderate MD which affected the
... Show MoreThe interest of many companies has become dealing with the tools and methods that reduce the costs as one of the most important factors of successful companies, and became the subject of the attention of many economic units because of the impact on the profits of company, and since the nineties of the last century the researchers and writers gave great attention to this subject, especially in light of the large competition and rapid developments in cost management techniques, as well as the wide and significant change in production methods that have been directed towards achieving customer satisfaction, all this and more driven by economic units in all sectors whether it is service or productivity to find methods that would reduc
... Show MoreThe developments and transformations taking place in the era and the growth of knowledge economies and communication technology led this development to compel higher education institutions in Iraq to reconsider their objectives to keep pace with development. And one of the most important tools of development was the application of e-learning standards and its long-term impact on the performance of the educational institution. Performance auditing plays an important role in verifying the extent to which these institutions have implemented their activities and programs that auditing performance by adopting e-learning standards helps the institutions’ management by providing appropriate information on the extent to which they achieve thei
... Show MoreFor a long time, the intensification of profit represented a major goal for the company management ,but this goal confirmed a series of restrictions such the constriction on short period, the time rather than on long and medium strategic goal, the relationships with customers ,the supplies, employees , This goal is replaced by another one (intensification of the company's value) ,and the fortune of the share holders itself ,for the purpose of creating value, the company must generate great outcomes to cover the operating expense and to insure the a suitable compensation to the invested capital (the market value added) is the indication used to estimate the company ability to create value –added the development
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