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 great raise and development of residential buildings in modern cities worldwide as a result of urban extends leads to environmental and social problems, that make the designers looking for more complicated and innovative solutions. To encounter these, most advanced technologies in construction had been used resulting buildings had become higher, which was moved away from the land called residential housing. And with the development of these buildings, increase in the inhabitants inside; generate distant from nature, which increased the need for interactive outdoor recreational spaces open green in its high sections, was an alternative or complementary option to outer space at the ground level. Therefore, the research problem has emer
... Show MoreThe aim of the current research is to identify the personal distance between members of society, as well as, to identify the feelings of satisfaction and positivity from respecting the permissible personal distance. The study also aims to identify the feelings of annoyance and comfort from approaching and going beyond personal distance and not respecting it. To achieve these goals, the researchers reviewed previous literature, theories, and studies that dealt with personal distance. The researchers reached a number of results; first, personal distance is not a law but rather a cultural guiding principle for social and professional morals. Second, there are four distances (intimate distance, the distance between friends, social distance,
... Show MoreA total of 722 algal taxa are recorded in Diyala River by different authors. Most of the identification algae belong to three Divisions: Bacillariophyceae (367, 50.8%), Chlorophyceae (179, 24.8%), and Cyanophyceae (126, 17.5%).
This research studies the conflict issue regarding climate rapid change as a fact which occupied scientists and specialists alike, who research in this particular field, especially in recent years and how this matter has been dealt with according to real and in fictional structures via films and TV.
The researcher dealt with two researches in this study :
The first : climate extremes, human and drama rituals.
The second : realistic and imaginary construction in the cinematographic medium.
The study is based on the analysis of the film "GeoStorm", which focuses on the issue of global natural storms and the dangerous weather phenomena that threaten our planet as a result of neglect and tampering
... Show MoreObjective: A descriptive design, using the methodological approach, is carried throughout the present
study from April 1st 2012 to May 20th 2013 to construct the school physical environment standardized
features tool.
Methodology: An instrument of (141) item is constructed for the purpose of the study. A purposive
sample of (44) school; (22) public and (22) private ones is selected. Content Validity of the instrument is
determined through the use of panel of (11) expert who are specialists in Community Health Nursing and
Community Medicine. Internal consistency reliability, using the split-half technique, is employed through
the computation of Cronbach alpha correlation coefficient of (0.93) for internal scale. Data
The electric submersible pump, also known as ESP, is a highly effective artificial lift method widely used in the oil industry due to its ability to deliver higher production rates compared to other artificial lift methods. In principle, ESP is a multistage centrifugal pump that converts kinetic energy into dynamic hydraulic pressure necessary to lift fluids at a higher rate with lower bottomhole pressure, especially in oil wells under certain bottomhole condition fluid, and reservoir characteristics. However, several factors and challenges can complicate the completion and optimum development of ESP deployed wells, which need to be addressed to optimize its performance by maximizing efficiency and minimizing costs and uncertainties. To
... Show MoreSome have considered the dialectic in form and meaning from different points of view, and dismantled them from each other, and this view is correct if we adopt according to the logic of Aristotle when it comes to dialectic, the dialectic of form and meaning has different aspects and does not share a single line in terms of conceptual meaning, the form is the appearance What the recipient sees with the help of cognitive tools, the content or content is the mental meaning, which in turn depends on his own tools, and to this extent this view is correct, and the intellectual content or meaning of the artwork or the human message that the artist wants to convey to the viewer.
The research included four chapters. The first chapter included
The research sheds light on an important religious sect that played a fundamental role in the structure of the Iraqi society in general and the Baghdadi society in particular, in which the Jews in general and the Jewish women in particular played an active role in the culture and heritage of Baghdadi society. The educational, cultural and artistic activity of Jewish literacy is a model for study.
one of the most important consequences of climate change is the rise in sea levels, which leads to the drowning of some low-lying island states, which leads to them losing the elements of statehood and thus affecting their status as a state, this resulted in several proposals made by the jurisprudence of international law to solve this issue, perhaps the most important of which is the idea of the government in exile, and the proposal to continue recognition of submerged countries, in a way that makes it possible to talk about a new concept of states represented by deterritorialized states, all of which are ultimately proposals that contain great difficulties that hinder their implementation in reality.