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 Search stressed on the importance of the role of property tax as a tributaries of the state budget that depend on it to cover the side of public expenditures, along with the rest of the other types of taxes through a review of the tax framework and tax proceeds and stand on the research problem and its effects, according to the following logic questions : -
- What is the contribution of property tax in the overall tax revenue?
- Are there any certain problems in collection of property tax?
3. What are the factors that lead to a negative impact on the outcome of the property tax?
4. How do we strengthen the role of the property tax in the overall tax revenue?
This r
... Show MoreTitanium dioxide TiO2 has been widely utilized in cleaning and sterilizing material for many clinical tools sanitary ware, food tableware and cooking and items for use in hospitals. Titanium dioxide TiO2 non toxicity and long term physical and chemical stability. It has been widely used decomposition of organic compounds and microbial organisms such as cancer cell, viruses and bacteria as well as its potential application in sterilization of medical devices. The aim of the study the effect of titanium dioxide TiO2 on some Gram negative bacteria and study their effects on some virulence factors and chromosomal DNA.In this study, we obtained (E. coli ? Proteus mirabilis, Proteus vulgaris ? Pseudomonas aeruginosa ? Klebsiella pneumonia and Ac
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The research talks about the interest and its impact on polygamy as a legitimate social psychological issue, where she talked about the concept of polygamy, and evidence of the legitimacy of polygamy, and clarify the conditions, and then touched on the great interests for which the law allowed polygamy, and mentioned some practical models in polygamy, including What is in the interest of men in pluralism, including in the interest of women in pluralism, including in the interests of both sexes in pluralism .
Skull image separation is one of the initial procedures used to detect brain abnormalities. In an MRI image of the brain, this process involves distinguishing the tissue that makes up the brain from the tissue that does not make up the brain. Even for experienced radiologists, separating the brain from the skull is a difficult task, and the accuracy of the results can vary quite a little from one individual to the next. Therefore, skull stripping in brain magnetic resonance volume has become increasingly popular due to the requirement for a dependable, accurate, and thorough method for processing brain datasets. Furthermore, skull stripping must be performed accurately for neuroimaging diagnostic systems since neither no
... Show MoreSkull image separation is one of the initial procedures used to detect brain abnormalities. In an MRI image of the brain, this process involves distinguishing the tissue that makes up the brain from the tissue that does not make up the brain. Even for experienced radiologists, separating the brain from the skull is a difficult task, and the accuracy of the results can vary quite a little from one individual to the next. Therefore, skull stripping in brain magnetic resonance volume has become increasingly popular due to the requirement for a dependable, accurate, and thorough method for processing brain datasets. Furthermore, skull stripping must be performed accurately for neuroimaging diagnostic systems since neither non-brain tissues nor
... Show MoreAbstract This research deals with the Al-Tossy contribution Islamic government and explain the directions of early shiaa political thoughts and knowing the opinions of Al-Shakh Al- Tossy in the Islamic Government
This research aims to identify the relationship between occupational hypocrisy and organizational strategic success, It was done by analyzing the correlations and influence between variables, applied to a random sample of university professors at the University of Kufa faculty of administration and economic.
The main tool for data collection is the survey were questionnaires were distributed randomly to the professors , and (43) questionnaires were returned, and test its validity by using (SEM) (Structural Equation Modeling), Hypothesis has been tested by using Statistical Package for Social Sciences (SPSS v. 18), The research found a set of conclusions:(The occupational hypocrisy has
... Show MoreThis study was carried out to measure the percentage of heavy metals pollution in the water of the Diyala river and to measure the percentage of contamination of these elements in the leafy vegetables grown on both sides of the Diyala river, which are irrigated by the contaminated river water (celery, radish, lepidium, green onions, beta vulgaris subsp, and malva). Laboratory analysis was achieved to measure the ratio of heavy element contamination (Pb, Fe, Ni, Cd, Zn and Cr) using flame atomic absorption spectrophotometer during the summer months of July and August for the year 2017. The study showed that the elements of zinc, chromium, nickel and cadmium were high concentrations and exceeded. The maximum concentration of these
... Show MoreDiscretionary Punishment, Public Regulation, Interest