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.
Current design codes and specifications allow for part of the bonded flexure tension reinforcement to be distributed over an effective flange width when the T-beams' flanges are in tension. This study presents an experimental and numerical investigation on the reinforced concrete flanged section's flexural behavior when reinforcement in the tension flange is laterally distributed. To achieve the goals of the study, numerical analysis using the finite element method was conducted on discretized flanged beam models validated via experimentally tested T-beam specimen. Parametric study was performed to investigate the effect of different parameters on the T-beams flexural behavior. The study revealed that a significant reduction in the
... Show MoreDue to its various resistance mechanisms, Pseudomonas aeruginosa is the most prevalent opportunistic infection that kills hospitalized patients. Thus, therapeutic options become limited. Objective: The study aimed to estimate the antibiofilm effectiveness of Conocarpus erectus leaf extracts against MDR P. aeruginosa isolates and examines pelA and algD gene expression. Subjects and Methods: One hundred-fifty clinical samples were collected from five Baghdad hospitals between September 2021 and January 2022. Samples were grown on different mediums. Despite cetrimide agar's ability to detect P. aeruginosa, only 83 isolates developed at 42°C. VITEK 2 compact system identification followed. This study examined 83 of P. aeruginosa isolates for r
... Show MoreReproduction potential and age –specific fecundity of the Mealybug Planococcus citri Risso were studied in the laboratories of Biological control research unit,college of Agriculture –Baghdad university at 25± 2Cº and 60-70% R.H.with 16 light:8 dark photo period.The results showed that the survival ratio began to decline at the 38th day, the average female age was 20 days ,while the average age was 8 days at the first reproduction . Net reproduction rate ( Ro ) was 58.59 female female generation which prove that the population of the mealybug was of the unstable kind , intrinsic rate of increase (rm) was 0.118 femalefemale and the average length period of generation ( T ) was 34.30 days . Many local predators attack the mealybug
... Show MoreThis study aims to investigate the academic leaders’ perceptions towards the degree of availability of the dimensions of organizational immunity systems at the University of Tabuk, as well as to reveal the statistically significant differences between the average responses of the study sample members about the degree of availability of these dimensions at their university due to the variables of (gender, leadership position, and college specialization). To achieve the objectives of the study, a descriptive survey method was used. The study population consisted of (200) male and female leaders who were academic leaders at the University of Tabuk. A questionnaire was used as a tool for collecting data, which its validity and reliability
... Show MoreIn line with the advancement of hardware technology and increasing consumer demands for new functionalities and innovations, software applications grew tremendously in term of size over the last decade. This sudden increase in size has a profound impact as far as testing is concerned. Here, more and more unwanted interactions among software systems components, hardware, and operating system are to be expected, rendering increased possibility of faults. To address this issue, many useful interaction-based testing techniques (termed t-way strategies) have been developed in the literature. As an effort to promote awareness and encourage its usage, this chapter surveys the current state-of-the-art and reviews the state-of-practices in t
... Show MoreIn line with the advancement of hardware technology and increasing consumer demands for new functionalities and innovations, software applications grew tremendously in term of size over the last decade. This sudden increase in size has a profound impact as far as testing is concerned. Here, more and more unwanted interactions among software systems components, hardware, and operating system are to be expected, rendering increased possibility of faults. To address this issue, many useful interaction-based testing techniques (termed t-way strategies) have been developed in the literature. As an effort to promote awareness and encourage its usage, this chapter surveys the current state-of-the-art and reviews the state-of-practices in t
... Show MoreThis research includes problems that facing the philosophy of education in the variables of knowledge and Informatics society (techno _ social).
The problematic research included three questions:
1- What are the concepts and characterization related to the problematic of relationship between the philosophy of education and informatics variables (techno - social).
2-What kind of problems facing speech philosophy of education in the variables information (techno - social)
3 - What are the perceptions of educational proposed to address problematic philosophy of education in the scope of human (human nature) and (values and morals), in addition the research may explain the co
... Show MoreEpilepsy is considered as one of the common neurological disorders.About 50 million persons have affected by epilepsy .Carbamazepine is one of the common drugs used by pregnant women with epilepsy. The aim of the present study is to investigate the effect of carbamazepine on the process of brain development during day 13 of pregnancy.Fifty pregnant albino mice have been used. They were divided into two groups. The control group that had been orally drenched with normal saline. The other group was treated group that had been given 15 mgKg of Carbamazepine orally. The fetuses have been collected after killing of the mice. Boun’s solution was selected as fixative. 5-8 µm thick sections from the fetuses were cut to be stained with hematoxyli
... Show MoreThroughout this paper, three concepts are introduced namely stable semisimple modules, stable t-semisimple modules and strongly stable t-semisimple. Many features co-related with these concepts are presented. Also many connections between these concepts are given. Moreover several relationships between these classes of modules and other co-related classes and other related concepts are introduced.
Inhibition of T cell derived cytokine production could help suppress osteoclast differentiation in inflammatory skeletal disorders. Bisphosphonates are typically prescribed to prevent inflammatory bone loss but are not tolerated by all patients and are associated with an increased risk of osteonecrosis of the jaw. In light of this other anti-resorptives such as phytoestrogens are being considered. However the effect of phytoestrogens on T cell-induced osteoclast formation is unclear. The effect of genistein and coumestrol on activated T cell-induced osteoclastogenesis and cytokine production was therefore examined. Concentrations of genistein and coumestrol (10−7 M) previously shown to directly inhibit osteoclast formation also suppressed
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