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.
Neural stem cells (NSCs) are progenitor cells which have the ability to self‑renewal and potential for differentiating into neurons, oligodendrocytes, and astrocytes. The in vitro isolation, culturing, identification, cryopreservation were investigated to produce neural stem cells in culture as successful sources for further studies before using it for clinical trials. In this study, mouse bone marrow was the source of neural stem cells. The results of morphological study and immunocytochemistry of isolated cells showed that NSCs can be produced successfully and maintaining their self‑renewal and successfully forming neurosphere for multiple passages. The spheres preserved their morphology in culture and cryopreserved t
... Show MoreIn this work, the effect of ceramic coating on performance, exhaust gas temperature and gases emissions of diesel engine operated on diesel fuel and biodiesel blends was investigated. A conventional four stroke, direct injected, single cylinder, diesel engine was tested at constant speed and at different load conditions using diesel fuel and biodiesel blends. The inlet and exhaust valves, the head of piston and cylinder head of the engine were coated by ceramic materials. Ceramic layers were made of (210-240) μm of Al2O3 and (30-60) μm of 4NiCr5Al as a bond coat for inlet and exhaust valves and (350-400) μm of YSZ and (50-100) μm of 4NiCr5Al as a bond coat for head of piston and (280-320) μm of Sic and (40-80) μm of 4NiCr5Al as a b
... Show MoreA new results for fusion reactivity and slowing-down energy distribution functions for controlled thermonuclear fusion reactions of the hydrogen isotopes are achieved to reach promising results in calculating the factors that covered the design and construction of a given fusion system or reactor. They are strongly depending upon their operating fuels, the reaction rate, which in turn, reflects the physical behavior of all other parameters characterization of the system design
The introduction of the research on the science of training and the physiology of sports was addressed from important sciences, where the physical effort drew the attention of scientists since the past centuries when they studied how the body performs its functions when performing physical exertion and observe the changes that occur in it and write down and study especially the positive effects of the practice of daily sports The aim of the study was to investigate the effect of plank exercises on the lipid component and the metabolic rate (bmr) of the female students of the Higher Institute for Security and Management Development. As for the third chapter, the two researchers used the experimental method on a sample of the female s
... Show MoreThe aim of the research is to know the effect of financial leverage on the market value of the stock by applying it to a sample of private Iraqi commercial banks listed in the Iraqi Stock Exchange for the period (2010-2019) and to show the extent of that effect, based on the bank’s annual reports for the mentioned period through the use of financial leverage ratios represented b (Equity multiplier, cash balance ratio), its discussion, analysis, description, inferential description, and testing of research hypotheses,
A set of conclusions has been reached, the most important of which are: The research sample banks depend in their financial structures on borrowed funds in a greater proportion than their r
... Show MoreBackground. Bone healing is a complex and dynamic process that represents a well-orchestrated series of biological events of cellular recruitment, proliferation, and differentiation. The use of medicinal plants in bone healing has attracted increasing interest because of their lower side effects. Punica granatum seed oil (PSO) contains high levels of phenolic compounds, promotes osteoblast function, and plays an important role in bone remodeling. A gelatin sponge (Spongostan) is a hemostatic agent that is extensively applied as scaffolds in engineering and as drug carriers in the medical field. This study aimed to evaluate the effectiveness of PSO for bone healing enhancement. Twenty adult male New Zealand rabbits, weighing an avera
... Show MoreIn this study a polymeric composite material was prepared by hand
lay-up technique from epoxy resin as a matrix and magnesium oxide
(MgO) as a reinforcement with different weight fraction (5,10,15,
and 20)% to resin. Then the prepared samples were immersed under
normal condition in H2So4(1 M) solution, for periods ranging up to
10 weeks. The result revealed that the diffusion coefficient
decreasing as the concentration of MgO increase. Also we studied
Hardness for the prepared samples before and after immersion. The
result revealed that the hardness values increase as the concentration
of MgO increase, while the hardness for the samples after immersion
in H2SO4 dec
In this study, the response and behavior of machine foundations resting on dry and saturated sand was investigated experimentally. A physical model was manufactured to simulate steady state harmonic load at different operating frequencies. The effect of relative density, depth of embedment, foundation area as well as the imposed harmonic load was investigated. It was found that the amplitude of displacement of the foundation increases with increasing the amplitude of dynamic force and operating frequency meanwhile it decreases with increasing the relative density of sand, degree of saturation, depth of embedment and contact area of footing. The maximum displacement was noticed at 33.34 to 41.67 Hz. The maximum displacement amplitude respons
... Show MoreIn this study, the response and behavior of machine foundations resting on dry and saturated sand was investigated experimentally. A physical model was manufactured to simulate steady state harmonic load at different operating frequencies. The effect of relative density, depth of embedment, foundation area as well as the imposed harmonic load was investigated. It was found that the amplitude of displacement of the foundation increases with increasing the amplitude of dynamic force and operating frequency meanwhile it decreases with increasing the relative density of sand, degree of saturation, depth of embedment and contact area of footing. The maximum displacement was noticed at 33.34 to 41.67 Hz. The maximum displaceme
... Show More