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:
The aim of the research is to demonstrate the impact of the salary localization service in enhancing banking competitive advantage. In order to achieve this goal, salary localization was chosen as an independent variable and its impact was studied on the dependent variable, which is the competitive advantage. The research problem lies in the fluctuation of the salary localization service from one bank to another and the impact of this on the competitive advantage. The study sample included five private Iraqi banks, namely (the National Bank of Iraq, the International Development Bank, Assyria International Bank, Al Khaleej Commercial Ban
... Show MoreOyster mushroom (Pleurotus ostreatus (Jacq. ex Fr.) P. Kumm.) is involved in the destruction of dead wood which is the main place of settlement of several living organisms. After humification, dead wood also becomes an important component of forest soils.
The purpose of the research is to study temperature and moisture conditions of extensive cultivation of oyster mushrooms on various wood substrates. To accomplish this goal, the following tasks were set: to determine the amount of effective stress temperatures and moisture content of substrates and their influence on the appearance of fruiting bodies of the oyster mushroom; to study the features of the extensive culti
... Show MoreIn this paper, the effects of prey’s fear on the dynamics of the prey, predator, and scavenger system incorporating a prey refuge with the linear type of functional response were studied theoretically as well as numerically approach. The local and global stabilities of all possible equilibrium points are investigated. The persistence conditions of the model are established. the local bifurcation analysis around the equilibrium points, as well as the Hopf bifurcation near the positive equilibrium point, are discussed and analyzed. Finally, numerical simulations are carried out, and the obtained trajectories are drowned using the application of Matlab version (6) to explain our found analytical
... Show MoreThe transition states that Iraq economy lived it after 2003, and the change in tools used by monetary policy based on C.B.I law 56 in 2004, under the especially situation for the economy (structural imbalances and the weakness of banking & financial sector).
The monetary policy adopted the inflation targeting policy to mantain the monetary stability in the economy and considered it an incubator for future growth. It used the exchange rate as a nominal anchor to achieve the goal (because the rentier of economy, finance Shallowness & separation between real sector and finance sector, all this cause the normal channel to transfer the effect of monetary policy (interest rate) ineffective.
... Show MoreWithin this work, to promote the efficiency of organic-based solar cells, a series of novel A-π-D type small molecules were scrutinised. The acceptors which we designed had a moiety of N, N-dimethylaniline as the donor and catechol moiety as the acceptor linked through various conjugated π-linkers. We performed DFT (B3LYP) as well as TD-DFT (CAM-B3LYP) computations using 6-31G (d,p) for scrutinising the impact of various π-linkers upon optoelectronic characteristics, stability, and rate of charge transport. In comparison with the reference molecule, various π-linkers led to a smaller HOMO–LUMO energy gap. Compared to the reference molecule, there was a considerable red shift in the molecules under study (A1–A4). Therefore, based on
... Show MoreThe research aims to examine the integration effect among resource consumption accounting (RCA) system and the enterprise resource planning (ERP) on both costs reduction and quality improvement. The study questioner form distributed to two different respondents as the unit of analysis. The research reached various conclusions most important of which is the integration relationship can help solve the special difficulties in managing the economic unit data. Moreover, the integration provides a clear picture of the causal relationships between resources, resource quantities, and associated costs
This paper was conducted to identifying the body growth averages for the infants of the age (3-6) months and their relation with brest (natural ) or artificial feeding The results showed that the higher percentage was for the infants with the natural feeding in comparison with those of the artificial or mixed feeding. Also there was a clear increase in the average of the body growth for those with the natural feeding and such results were closer to the standard criterion. While the averages of body growth for those with the artificial or mixed feeding were low. In addition, it was clear that the averages of body growth of the i
... Show MoreThe aim of the current research is to identify the impact of the SWOT strategy on developing systemic intelligence among students of the Ibn Rushd College of Education for Human Sciences University of Baghdad / College of Education Ibn Rushd for Human Sciences. The current research community consists of (8590) male and female students, divided into (7) departments. The current research relied on one of the partial control designs, which is the design of non-random groups: experimental group and a control group with a pre and post-test. As for the research tool, It was represented by Tourmanin’s Systemic Intelligence Scale (2012) of (50) items that measure the eight components of systemic intelligence. The results of the Mann Whitney te
... Show MoreIs the efficiency of physical and your endurance is of great importance for some activities and field, as it whenever the situation has improved student career was able to perform physical exertion more with energy saving efforts, so the identification of physical aptitude and endurance private students, was based on that there are positively correlated the carrying of training and pregnancy fact on the shoulders of the student. In other words, physical aptitude and endurance in your control level that can be shown by the student during the performance of training and competitions. Therefore, lies the importance of research to test physical aptitude and endurance your help to reveal the career of the body in the light of their relationship
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