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 transformational leaderships in all organizations consider Motivations policies which is one of the main and basic policies adapted by the successful leaderships in all organizations, in order to be able to achieve essential goals, such as enhancing loyalty of employees towards their organizations and also developing and empowering their capacities and abilities in work, leading to development and increasing productivity and reducing production costs to the minimum, then reaching immense profits and benefits, in addition to development of excellence in the market of competition.
The research was performed in the (General Company of Leather Industries/ in Baghdad ,in alkarada) the study reached
... Show Morebstract This study was performed to isolate and identify the Burkholderia cepacia from rhizosphers of different plants and study their ability to produce Siderophore, the study was also aimed to assess the antifungal activity of the bacterial filtrate and extracts of the isolates against some pathogenic fungi. The isolate which showed higher inhibitory effects was selected for extraction of some active metabolites produced by it, and evaluate the activity in vitro, via inhibition of the growth of the fungi using different concentrations of extract (50, 100, 200 )µL/ml , The results showed that out of (250) samples of soil , (8) isolates (3.2%) gave positive
... Show MoreThe parametric programming considered as type of sensitivity analysis. In this research concerning to study the effect of the variations on linear programming model (objective function coefficients and right hand side) on the optimal solution. To determine the parameter (θ) value (-5≤ θ ≤5).Whereas the result، the objective function equal zero and the decision variables are non basic، when the parameter (θ = -5).The objective function value increases when the parameter (θ= 5) and the decision variables are basic، with the except of X24, X34.Whenever the parameter value increase, the objectiv
... Show MoreThis research aims to identify the nature effect of some mechanisms governance in the Accounting Conservatism for a sample of the practices of companies (banks) in the Iraq Stock Exchange and identify any of this mechanics most effects in the accounting Conservatism. To achieve this objective the use of all of it (the size of the board of directors, management ownership, ownership concentration, the auditor's report) as independent variables was used model Basu revised to measure the Accounting Conservatism , which was considered a variable follower with taking into account the effect of the control variables represented by the (company size and leverage) of a sample of listed on the Iraq Stock Exchange companies for the pe
... Show MoreSome specific factors that cause the kinetic compensation effect
during the decomposition CaC03 are identified. The role of the C02 equilibrium pressure is examined in relation to the kinetic compensation effect. This investigation also shows why non - iso thermal experiments have some time necessarily to yield value of activation energy different from the value obtained from isothermal experiments.
The education, especially higher education, is an essentially factor in the progress of any society, if we consider the higher education, represents the top of the education`s pyramid which take part in developing the human resources and provide the human staff to raise the productive efficiency, and improve the social , economic level
In order to face the increasing importance of higher education, great capabilities and expenditures must be available in a continous way, such expe
... Show MoreThis paper represent the second step i n a molecular clon i ng program ai ming to clone large DNA fi·agmen ts of the sal t tolerant bermudagrass (Cyrwdon dactylon L.) DNA usi ng the bacteriophage (EM13L3) as a vector.
In th is work, a yield of about I 00 g bacteriophage DNA per one liter culture.was obtained with.a purity ranging between (1.7-1.8). The vector JJNA v.as completely double digested with the restriction enzymes llamHI and EcoRI, followed by pu
... Show MoreThe central nervous system is the most important system and is very sensitive to any accidental infection during ontogenesis; it includes brain and spinal cord. The cerebellum is the second largest part of the brain after cerebrum and it’s very sensitive to the abnormal changes during the embryological development. This study was designed to investigate the effect of the maternal exposure of selected concentrations of suspension of nanoparticles on the ontogenesis of the rat cerebellum after embryos implanted in uterus.
A total of 60 female pregnant rats were divided in to three groups, each contains 20 females. Group1 (G1) was treated orally with 2mg/kg /body weight (b. wt) of
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