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.
Covalent modification of protein by drugs may disrupt self-tolerance, leading to lymphocyte activation. Until now, determination of the threshold required for this process has not been possible. Therefore, we performed quantitative mass spectrometric analyses to define the epitopes formed in tolerant and hypersensitive patients taking the β-lactam antibiotic piperacillin and the threshold required for T cell activation. A hydrolyzed piperacillin hapten was detected on four lysine residues of human serum albumin (HSA) isolated from tolerant patients. The level of modified Lys541 ranged from 2.6 to 4.8%. Analysis of plasma from hypersensitive patients revealed the same pattern and leve
This book presents the problem of tooth decay due to bacteria Streptococcus mutans one of methods of treatment using 3 extracts of S. persica (miswak) (aqueous, acetone and methanol) and prove its effectiveness and its impact on the gtf (B, C, and D) genes that code the glucosyltransferase (Gtf) enzymes that cause decay membrane compared to the usual means used for the prevention of tooth decay
The dried fruit peel of pomegranate in Punicaceae family was fractionated chromatographically on Sephadex-LH-20 column .Gallic acid (trihydroxybenzoic acid) and its related galloyl esters such as gallotannin(i.e. β-penta-O-galloyl–D-glucose) were obtained homogenously. Different concentrations of gallic acid and gallotannin were used to determine their inhibitory effect on human serum cholinesterase. The enzyme activity was measured according to the method reported by the WHO .The inhibitory effect of these compounds on the activity of human serum cholinesterase have been studied in vitro .The inhibitory effect was remarkably clear with increasing concentration of gallic acid .Whereas galloyl ester showed n
... Show MoreThe study was performed to isolate and identify the Myxococcus fulvus from the one hundred samples of soils of farms. Special growth conditions had been used to support the growth of M.fulvus local isolates and suppressed the growth of other microorganisms like (Drying , High Temperature , High concentration of antibiotics and specific growth media ) M.fulvus isolates had been subjected to the morphological, cultural , biochemical examination for identification , as well as , study the inhibitory activites of cells and filtrates of localized isolates against some pathogenic fungi include (Trichophyton mentagrophytes , Microsporum gypseum , Aspergillus niger and Fusarium oxyporum ) by using three methods :- Cup assay , well diffusio
... Show MoreRegulatory T (Treg) cells are one of the major immunosuppressive cell types in cancer and a potential target for immunotherapy, but targeting tumor-infiltrating (TI) Treg cells has been challenging. Here, using single-cell RNA sequencing of immune cells from renal clear cell carcinoma (ccRCC) patients, we identify two distinct transcriptional fates for TI Treg cells, Fate-1 and Fate-2. The Fate-1 signature is associated with a poorer prognosis in ccRCC and several other solid cancers. CD177, a cell surface protein normally expressed on neutrophil, is specifically expressed on Fate-1 TI Treg cells in several solid cancer types, but not on other TI or peripheral Treg cells. Mechanistically, blocking CD
Most cultivars of sorghum have low field emergence as common problem. Three experiments were carried out at Agriculture College, Baghdad University. First experiment was conducted in laboratory according to Complete Randomized Design (CRD) with four replicates. Second and third experiments were conducted at field according to Randomized Complete Block Design (RCBD) during the spring and the fall seasons of 2015, respectively, with four replicates for each one. Same two factors were studied at each experiment. First factor was seed priming by seed soaking for 10 hours in distilled water, solvents of GA3, KCl and thiamine (300, 40 and 30 mg*L-1, respectively) and non-primed seed. Second factor was three cultivars of sorghum (Inqath, Kafier an
... Show MoreThe results of the phytochemical analysis of the crude aqueous and
methanolicextracts of Myrtle (Myrtuscommunis), peppermint (Menthapiperita) and
Sweet basil(Ocimumbasilicum) contain active compounds : Phenols, Flavonoids and
Tannins and missing of Steroids and Coumarines in all extract but Saponins and
Alkaloids found in methanolicextract only, while terpens were present in peppermint
and basiland absent in Myrtle. Administratingto animals with different extracts
showed no effect on serum Acetylcholinesterase (AchE) compared withthese fed on
ethanol liquid diet, Methanolicand aqueous extracts of Myrtle, peppermint and
basilin the serum of decreased Acetylcholinesterase level significantly(p≤0.05)[(1.25
ΔpH/
The research aimed at studying the inhibitive effect of the hot watery dry and ethanolic ginger(85%) and fragrant oil which are added in concentrates of o.o25, o.o5o and 0.1g / 100g respectively in the growth of bacteria and molds. The results of the initial chemical diagnosis showed containment of ginger roots extract on. Alkaloids, Glycosides, Flavonoids and Suponins. The highest inhibitive effect of the bacteria reached the concentrate . 0.1% of the oil extract then the concentrate 0.050% of the ethanolic hot extract follows it. While 0.1% was the least inhibitive concentrate for the hot watery extract. But the inhibitive effect of the hot oily and alcoholic extracts in the numbers of molds colonies was 0.025%, when the concentrate 0.1%
... Show MoreRepresents light a sovereign and importance in cinematography element of what possessed the physical characteristics make it a sharp image detail or opaque, or any other form as he wants the director, Valdu away from the main function, which emerged with the beginnings of cinema, any access to endanger the proper and good, the Alachtgalat dramatic and psychological are deepened performance lighting and functioned in adjacent with the shadows, all the two complement each other, which affects the image details or even the ability to express their personal depths or the social and psychological same place, and this prompted the researcher to determine the search in the following address: (employing lighting to express their personal duplica
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