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 is a descriptive study that used the survey method, it’s aimed to identify the topics and frameworks of diplomatic and political issues covered by the news of the website of the Iraqi Ministry of Foreign Affairs, through the content analysis method applied on a sample selected in a systematic random manner for news published in the year 2021. The sample included (191) news equivalent to (20%) of the total study population of (942). The study reached some results, the most important of which were as follows: The political issue, in its general sense, grabbed the most prominent attention among the various issues and events focused on by Iraqi diplomacy: "international cooperation", "bilateral cooperation", and then "regional politic
... Show MoreBackground: This study was conducted to assess the effects of various beverages on the shear bond strength of light-cured orthodontic composite used to bond stainless steel orthodontic brackets on human teeth and to determine the site of bonding failure of this material. Materials and Methods: Fifty extracted human premolars were selected and randomly divided into five equal groups each with 10 teeth according to the beverage type (Control, One Tiger, Milk, Green tea and Coffee). After bonding, the teeth were immersed in specific beverages for 5 minutes twice daily with equal intervening intervals then washed and stored in distilled water at 37º C for the reminder of the day. The process was carried out for 30 days. The samples were then
... Show MoreThe highest incidence of injury is seen in adolescent playing pivoting sports such as soccer, basketball, and handball. Objective: To examine the effectiveness of a neuromuscular prevention program in reducing knee and ankle injuries in adolescent male soccer players.
Abstract
Through this study, I tried to identify the grammatical efforts of one of the most important authors of the footnotes that were built on the luminous benefits marked with (Explanation of Mulla Jami in Grammar), and he is Sheikh Isamah Allah Al-Bukhari, who died in the eleventh century AH, trying as much as possible to stay away from the path of tradition in repeating the efforts of Those who preceded me in explaining the grammatical efforts of many grammarians, and perhaps what helped me in this is the characteristics that characterize the notes owners that may distinguish them from other owners of grammatical authorship, as a result of what characterized the personality of the notes owners from the predominance of the in
... Show MoreIn this research , pure Cadmium Oxide thin films were prepared by thermal evaporation Under vacuum method , where pure cadmium metal was deposited on glass Substrate in Room temperature (300K) at thickness (400 ± 30) nm with Deposition rate(1.1 ± 0.1) nm/sec And then we oxidize a pure cadmium Film in Temperature ( 350ºC ) for one hour with existence air flow. This research contained study of the influence of doping process by Tin metal (Sn) with two different ratios (1,3) % at substrate temperature (473K ) on th
... Show MoreThe purpose of the research is to investigate the response of stock prices of companies that issued debt instruments (bonds) listed on the Abu Dhabi Securities Exchange for information content from the Moody's first credit rating announcements for the period 1 January 2005 - 30 May 2017. The study methodology was used to verify the existence of this response by the market and the Market efficiency of the Semi-strong shape. The research focused on testing the impact of the initial announcement.The research showed that there is an influential information content to announce credit ratings in stock prices, with different responses between negative and positive. It was also found that the industrial sectors sample research separately d
... Show MoreThe aim of this research is to find out the impact of cognitive incompatibility schemes on the development of creative thinking skills among first grade students.
To prove the objective of the research, the researcher put the following hypothesis:
There is no statistically significant difference at the level of (0.05) between the average score of the experimental group who study the history of ancient civilizations according to the patterns of cognitive conflict and the average grades of the control group students who study the same subject in the usual way in the test of post-creative thinking skill
The importance of the research from a practical point of view lies in the fact that it presents a set of statistics and data that give a clear picture of how the Iraqi newspapers (the subject of the study) deal with the visit of "Pope Francis" to Iraq ، and what are the most prominent indicators and manifestations of that visit in promoting societal peace among the Iraqi public. From a scientific point of view، the research provides another scientific addition to the media library، especially with regard to journalistic treatments and methods of framing the Arab international press for the subject of the visit، which could be a starting point for other researchers to complete qualitative research in this field. The research prob
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