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.
Asthma is a chronic respiratory disorder in which immunological and structural cells play a role. The limits of conventional medicines necessitate the development of innovative therapeutic techniques for asthma. In the present study, we investigated the possible protective effect of cinnamic acid (CA) on ovalbumin-induced asthma in a mouse model. Sixty albino male mice BALB/c type weighing (20-30) grams were chosen at random and divided into five groups each one contains 12 animal: Group I: PBS/liquid paraffin control. Group II: asthma model group. Group III: cinnamic acid control group; mice received cinnamic acid (50 mg/kg) in liquid paraffin orally by gavage. Group IV: asthma model / group of (25 mg / kg) cinnamic acid; mice received
... Show MoreExperimental and numerical studies have been conducted on the effects of bed roughness elements such as cubic and T-section elements that are regularly half-channel arrayed on one side of the river on turbulent flow characteristics and bed erosion downstream of the roughness elements. The experimental study has been done for two types of bed roughness elements (cubic and T-section shape) to study the effect of these elements on the velocity profile downstream the elements with respect to different water flow discharges and water depths. A comparison between the cubic and T-section artificial bed roughness showed that the velocity profile downstream the T-section increased in smooth side from the river and decrease in the rough side
... Show MoreThis study deals with the subject of violence, but from another perspective, it has not been emphasized in contemporary studies of violence in Arabic and raqi universities, which is the structural or institutional aspect of violence. Traditional studies have focused their analysis of violence on the direct side the violence, The other side of the violence is the hidden violence, which is characterized by a lack of clarity of the underlying factors and its effects are not arises, which makes it the most serious violence, which requires a deep research into the social, political, economic, cultural and psychological structure of society (individuals and institutions). This study was based on the theory of the Norwegian scientist (J
... Show MoreThe dynamic behavior of laced reinforced concrete (LRC) T‐beams could give high‐energy absorption capabilities without significantly affecting the cost, which was offered through a combination of high strength and ductile response. In this paper, LRC T‐beams, composed of inclined continuous reinforcement on each side of the beam, were investigated to maintain high deformations as predicted in blast resistance. The beams were tested under four‐point loading to create pure bending zones and obtain the ultimate flexural capacities. Transverse reinforcement using lacing reinforcement and conventional vertical stirrups were compared in terms of deformation, strain, and toughness changes of the tes
Abstract:
We can notice cluster data in social, health and behavioral sciences, so this type of data have a link between its observations and we can express these clusters through the relationship between measurements on units within the same group.
In this research, I estimate the reliability function of cluster function by using the seemingly unrelate
... Show MoreThe electrocardiogram (ECG) is the recording of the electrical potential of the heart versus time. The analysis of ECG signals has been widely used in cardiac pathology to detect heart disease. The ECGs are non-stationary signals which are often contaminated by different types of noises from different sources. In this study, simulated noise models were proposed for the power-line interference (PLI), electromyogram (EMG) noise, base line wander (BW), white Gaussian noise (WGN) and composite noise. For suppressing noises and extracting the efficient morphology of an ECG signal, various processing techniques have been recently proposed. In this paper, wavelet transform (WT) is performed for noisy ECG signals. The graphical user interface (GUI)
... Show MoreSingle-input Multiple-output Signals Third-order Active-R Filter for different Circuit Merit Factor Q Configuration is proposed. This paper discusses a new configuration to realize third-order low pass, band pass and high pass. The presented circuit uses Single-input Multiple-output signals, OP-AMP and passive components. This filter is useful for high frequency operation, monolithic IC implementation and it is easy to design .This circuit gives three filter functions low-pass, high-pass and band-pass. This filter circuit can be used for different merit factor (Q) with high pass band gain. This gives better stop-band attenuation and sharper cut-off at the edge of the pass-band. Thus the response shows wider pass-band. The Ideal value of thi
... Show MoreSynthetic polymers such as polyurethane are used widely in the field of biomedical applications such as implants or part of implant systems.
This paper focuses on the preparation of base polymer matrix composite materials by (Hand Lay-Up) method, and studying the effect of selected grain size (32, 53, 63, 75, and 90) µm of (Reenia) particles on some properties of the prepared composite.
Mechanical tests were used to evaluate the prepared system (Tensile, Compression, Impact, and Hardness) tests, and a physical test of (Water absorption %), and all tests were accomplished at room temperature.
Where results showed tensile test (maximum tensile strength and modulus of elasticity) high at small grain size while
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