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.
The aim of this paper is to find out the effects of the strategy of productive thinking upon the student’s achievement for the subject of research methodology in the College of Islamic Sciences. Achieving this objective, the researchers set the null hypotheses: (1) No difference is noticed to be statistically significant at the level of significance (0.05) among the student’s mean scores in the experimental group who were taught by the strategy of productive thinking, and the student’s mean scores in the control group who studied by the traditional method in the achievement test. (2) At level of sig. (0.05), there is no statistically significant difference in the mean of scores of the pre-tests and post ones in the achievement test of
... Show MoreThe aim of this paper is to find out the effects of the strategy of productive thinking upon the student’s achievement for the subject of research methodology in the College of Islamic Sciences. Achieving this objective, the researchers set the null hypotheses: (1) No difference is noticed to be statistically significant at the level of significance (0.05) among the student’s mean scores in the experimental group who were taught by the strategy of productive thinking, and the student’s mean scores in the control group who studied by the traditional method in the achievement test. (2) At level of sig. (0.05), there is no statistically significant difference in the mean of scores of the pre-tests and post ones in the achievement test of
... Show MoreMake a search on the vegetative parts of the plant local horse guilt of some elements in the Haj Omran area in northern Iraq has included recognition of certain nutrients
The service system has become a necessity of life in modern cities to be the most basic necessities of modern humans, they constitute a major base, which is based on the sustainability of life in the city and a standard measured through the degree of well-being and progress of civilized peoples and their interaction with the surrounding environment, making the services sector as a need not be an option, whenever the cities widened in population and space whenever provision of services and upgrading the quality and quantity more pressing, which made the subject of the services takes the biggest area of the trends and thinking of urban planners and those who in charge of drawing the cities policies. Consideri
... Show MoreSome children are suffering from introversion in kindergartens , so it must be confront and obviated by specialists because it will inevitably lead to unsatisfactory results reflect negatively on the individual and the community together . And the introvert child is a miserable child incapable of social interaction or give - and - take with colleagues , lack of integration of the child to life leads to the obstruction of participation with his peers in various activities. Introversion causes a real emotional deficit to the children of kindergartens which limits of possibility of their intellectual development and mental growth and that because of their isolation and poor focus in education
... Show MoreThe avoidance strategy of prey to predation and the predation strategy for predators are important topics in evolutionary biology. Both prey and predators adjust their behaviors in order to obtain the maximal benefits and to raise their biomass for each. Therefore, this paper is aimed at studying the impact of prey’s fear and group defense against predation on the dynamics of the food-web model. Consequently, in this paper, a mathematical model that describes a tritrophic Leslie-Gower food-web system is formulated. Sokol-Howell type of function response is adapted to describe the predation process due to the prey’s group defensive capability. The effects of fear due to the predation process are considered in the first two levels
... Show MoreIn the last few years, there have been a lot of changes in the economy, society, and the environment. This has led to much competition between companies, directly and indirectly affecting production and marketing processes. Most companies are trying to cut production and manufacturing costs by using modern cost techniques such as product life cycle costing and Continuous Improvement (Kaizen) technology, in the method of measuring production costs or service costs, and the need for internal control to keep an eye on how these technologies are being used and how well they work. And to find out the effect of internal control on the implementation of costing techniques in Iraqi companies, 64 questionnaires were given to people who work in the i
... Show MoreAbstract
The aim of the research is to demonstrate the role of uncertainty in adopting the general requirements for the strategic environmental assessment of service departments in Babil Governorate and the Environment Department. By focusing on a range of environmental problems, despite the efforts exerted to deal with the environme
... Show MoreChina's economic policy and its huge capabilities operate according to an expansion strategy, especially in investing foreign projects, as the past ten years have witnessed a major development in the elements of comprehensive strength, especially in the economic field, in 2014 China launched the largest initiative in the world, represented by the Belt and Road Project (BRI), which links nearly 70 countries, through this project, a very important region has emerged, which is (the port of cadres) in Pakistan, as China has headed towards that region and given the highest importance that is in its interest in the first place regardless of the great Pakistani interest, This is consistent with its future aspirations, especially after breaking
... Show More