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 paper is mainly concerned with the study of the moral aspects that prompts William Shakespeare to attempt a romance in which he has embedded the epitome of his thought, experience, and philosophy concerning certain significant aspects of human life whose absence or negligence may threaten human existence, peace, and stability. From the beginning of history man realizes the importance of prosperity on the many and various levels that touch and address his needs and desires—natural, material, and spiritual. The Tempest, due to the dramatist's awareness of the aforementioned values, reflects the dramatist's duty as to projecting and unfolding these important aspects, reconciliation and forgiveness, that promote prosperity which is th
... Show MoreIn this work (paper), we investigate about the robustness of the modified divergence Information Criterion (MDIC), which proposed by Mantalos, Mattheou and Karagrigoriou (2008), to determine the probability of the Criterion picking up the true lag for Autoregressive process, when the error term of this process is normally and Non normally distributed. We obtained the results for different sample sizes by using simulation.
A class of hyperrings known as divisible hyperrings will be studied in this paper. It will be presented as each element in this hyperring is a divisible element. Also shows the relationship between the Jacobsen Radical, and the set of invertible elements and gets some results, and linked these results with the divisible hyperring. After going through the concept of divisible hypermodule that presented 2017, later in 2022, the concept of the divisible hyperring will be related to the concept of division hyperring, where each division hyperring is divisible and the converse is achieved under conditions that will be explained in the theorem 3.14. At the end of this paper, it will be clear that the goal of this paper is to study the concept
... Show MoreThis paper is mainly concerned with the study of the moral aspects that prompts William Shakespeare to attempt a romance in which he has embedded the epitome of his thought, experience, and philosophy concerning certain significant aspects of human life whose absence or negligence may threaten human existence, peace, and stability. From the beginning of history man realizes the importance of prosperity on the many and various levels that touch and address his needs and desires—natural, material, and spiritual. The Tempest, due to the dramatist's awareness of the aforementioned values, reflects the dramatist's duty as to projecting and unfolding these important aspects, rec
... Show MoreThe importance of television has emerged as an effective and influential force in the lives of societies and peoples, And not just a professional media since the fifties of the twentieth century, It was used as a platform to achieve the goals and objectives of the media and politics for governments, agencies and individuals in different countries of the world, Using many methods, methods and techniques that later became important major subjects and curricula and a scientific specialization that was founded for him to study and teach in most international universities, The media, especially television and satellite channels, play an active and significant role in managing crises and conflicts and directing them through the methods of deal
... Show MoreOften requires the investor to know the result of the company's activity contribute to the investor or by wanting to invest in them because profit or loss of the company affect positively or negatively in the price of shares of the company and with the end of the fiscal year delayed companies often to issue its financial statements after it is approved and audited by an observer External Auditor, From here came the idea of research that appears to stakeholders of financial statements proactive appear, including actual figures for earlier stages have been prepared lists about lists and planned by the administration reflect the results of its phase remainder of the year as if they are (half a year or season or month) to offer At the
... Show MorePurpose: The research aims to diagnose the current availability of knowledge workers characteristics and the role of these characteristics in knowledge acquision in the city of Sulaimaniya Directorate of Electricity, and to identify the differences between personal and occupational characteristics of a sample of research and its impact on the availability of such properties.Design/methodology/approach :to achieve the objectives of the research questionnaire was developed especially for it and then distributed to a sample of engineers and technicians working in the Directorate of Electricity city of Sulaimaniya, where the sample of the research (52) respondents.
Findings: the most important conclusions reached
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This research aims to shed light on the necessity of establishing an information security management system through which banking security risks are managed in the light of the ISO (IEC 27001) standard, through which bank departments seek to demonstrate the management of their security systems and their controls in accordance with the specifications of the standard to obtain an internationally recognized security certificate And the need for senior management in banks to an independent person with scientific and practical qualification and who has accredited certificates in the field of information technology for the purpose of helping them to verify the level of compatibility between the policies and procedures applied and the p
... Show MoreThe Objective of the research is to identify the Strategic Vigilance and effect in the Managerial Decision Quality, by knowing the interest of the organization influence the Strategic Vigilance in the Managerial Decision Quality, adopted four dimensions of the Strategic Vigilance is (Environmental Vigilance, Commercial, Competitiveness & Technology) to indicate the extent individually and collectively impact in the Managerial Decision Quality, The questionnaire was used as a main tool to survey the views of a sample of 45 managers, was named Supreme Judicial Council society for research, and the statistical program SPSS, and research found a clear positive impact dimensions Strategic Vigilance in the Manageri
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