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:
We can notice cluster data in social, health and behavioral sciences, so this type of data have a link between its observations and we can express these clusters through the relationship between measurements on units within the same group.
In this research, I estimate the reliability function of cluster function by using the seemingly unrelate
... Show MoreThe current research seeks to identify the impact of Barman's model on acquisition of the concepts of jurisprudence of worship among students of the departments of Qur'anic sciences. To achieve the research objectives, the researcher relied on the experimental method through a design with partial control by relying on two experimental groups receiving teaching by using the Barman model and a control group receives teaching through the normal method. After applying the experiment, the study reached the following results: Students of the Department of Qur’anic Sciences in general need educational programs linked to the curriculum and built on scientific foundations, according to their needs and problems (psychological, cognitive, and soc
... Show More— In light of the pandemic that has swept the world, the use of e-learning in educational institutions has become an urgent necessity for continued knowledge communication with students. Educational institutions can benefit from the free tools that Google provide and from these applications, Google classroom which is characterized by ease of use, but the efficiency of using Google classroom is affected by several variables not studied in previous studies Clearly, this study aimed to identify the use of Google classroom as a system for managing e-learning and the factors affecting the performance of students and lecturer. The data of this study were collected from 219 members of the faculty and students at the College of Administra
... Show MoreAbstract
This paper represents a study of the effect of the soil type, the drilling parameters and the drilling tool properties on the dynamic vibrational behavior of the drilling rig and its assessment in the drilling system. So first, an experimental drilling rig was designed and constructed to embrace the numerical work.
The experimental work included implementation of the drill-string in different types of soil with different properties according to the difference in the grains size, at different rotational speeds (RPM), and different weights on bit (WOB) (Thrust force), in a way that allows establishing the charts that correlate the vibration acceleration, the rate of penetration (ROP), and the power
... Show MoreThis study aimed to investigate the Microbial Load of Indian Meat available in
local market of Baghdad city to ensure that they are free from bacteria and to
indicate the safety of product depending on the Iraqi standards. in addition to the
estimation of some elements such as (Iron, Copper, Lead, Cadmium, Chrome) , we
gathered 30 trade brands of meat included: (Khairat Karbala1,Khairat Karbala2,
Thamarat Karbala1, Thamarat Karbala2, Alwakeel1, Alwakeel2, Anbar, Anwar
Karbala, Alfakher, Alraudhatain, Almurad, Zamzam, Rayat, Karbala, Karbala,
Alanna1,SAS,Alahmed,MKR,Altamam,Anwar,Almuntathr,Alwesam,Albayader,Am
bar,Thamarat Karbala,Alhalal,Alanwar,Alhana,Alfakher,Alana2).the bacteriological
test for these sample
Derivative spectrophotometry is one of the analytical chemistry techniques used
in the analysis and determination of chemicals and pharmaceuticals. This method is
characterized by simplicity, sensitivity and speed. Derivative of Spectra conducted
in several ways, including optical, electronic and mathematical. This operation
usually be done within spectrophotometer. The paper is based on form of a new
program. The program construction is written in Visual Basic language within
Microsoft Excel. The program is able to transform the first, second, third and fourth
derivatives of data and the return of these derivatives to zero order (normal plot).
The program was applied on experimental (trial) and reals values of su
The work of this paper is an investigation to improve the condenser performance of the automobile air conditioning system by enhancing the air-side heat transfer from the condenser through the use of an air guide net installed in front of the condenser face which is basically an aluminum plate having a circular entrance shape for the air passage. The A/C system was examined under two types of test. The first test was conducted the air guide net, while the second was done with the air guide net. The performances of the A/C system under these tests were compared. For the second type of test, the experiment was carried out with three different size of air guide net, three different circular diameters (2, 3 and 3.5 cm) a
... Show MoreThe current study was conducted to determine the sensitivity of some pathogenic bacterial isolates isolated from wounds and burns water toward the disposer of the Yas Rue tested five crude bacterial isolates isolated from wounds and burns which these isolates sensitive to aqueous extract crude
Background: Psychological stress is considered the major etiological factor precipitating myofacial pain and temporomandibular disorders.It is known that stress induce various adaptational responses of physiologic systems. The process includes increase in the activity of the hypothalamic-pituitary-adrenal axis which promotes cortisol secretion. Salivary cortisol has been used as a measure of free circulating cortisol levels.The use of salivary biomarkers has gained increased popularity since collecting samples is non-invasive and painless. The aim of thisstudy was to evaluate the level of cortisol in saliva among sample of university students having myofacial pain, during the final exam period and whether this finding could have a significa
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