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 compound chalcon originally is extracted form some plant and herbs, the studies of the antiviral activity of this compound were done in two cell line cultures the L2OB and RD, the compound relatively non toxic to both cell lines of the concentration of 32?g/ml or less ,the compound have significantly anti poliovirus activity in both L2OB cell line and RD cell line, we find that the concentration of 0.03 ?g/ml or more inhibit the 100TCDID50 of the poliovirus .The therapeutic index(TI)used in this study to evaluate the drug activity ,( TI is the ratio of dose of drug which is just toxic to the cells to the does which is just inhibit the viral multiplication, if this index more than one the margin of safety of drug is according great ) .In
... Show MoreKlebsiella pneumoniae have an ability to form biofilm as one of strategies to persist and overcome host defenses. The study aims to evaluate the effectiveness of rosemary essential oil alone and in combination with some antibiotics against biofilm of K. pneumoniae isolated from urine. The antibiotics resistance pattern by disc diffusion method and minimal inhibitory concentration (MIC) of gentamicin, ciprofloxacin, amoxicillin, trimethoprim/ sulfame- thoxazole, cefotoxime and rosemary essential oil were determined. The ability to form biofilm as well as inhibition of biofilm formation of K. pneumoniae was performed. MICs 128, 0.25, 768, 64, 384 and 10 µg/ml were used. The effect of MIC and 1/2 MIC of antibiotics and rosemary essential oil
... Show MoreThe aim of present study to investigate the effect of Coraindrum sativum leaves extract on reproductive activity of male albino mice .Thirty male mice with age of 80-100 day and weight between 25-30 g were divided into three groups: group 1 (untreated), group 2 and 3 were administrated orally for 30 days with aqueous extract of Coraindrum sativum leaves at dose 125 and 250mg/kg.b.w. respectively. The following parameters were evaluated: serum testosterone levels, testes weights, sperm characteristics [motility, viability, spermatozoa, morphology and concentration] and histology changes of the testis. The results showed that the treatment caused highly significant degrease (P<0.01) in testosterone levels and the weight of testes assoc
... Show MoreBackground: Nicotine is the foremost chemical constituent responsible for addiction in tobacco products, in the non-ionized condition can be easily absorbed via epithelial tissue of the lung, the mouth, the nose and across the skin
Objective:The study examines the harmful effect of the nicotine which is an important component of cigarette in vitro.
Type of the study: Cross-sectional study.
Methods: Examines the harmful effect of the nicotine which is an important component of cigarette in vitro by using two types of lung cancer cell lines (H460 TP53+/+, H441 TP53-/-).
Background: There is plenty of evidence
suggesting that involvement of several groups of
viruses in the development and / or acceleration of
Type 1 Diabetes Mellitus (T1DM).
Objective: To analyze the T- cell proliferation in
the presence of Coxsackie virus B5 (CVB5), Polio
and Adenovirus antigens in addition to assessment
of Interferon- gamma (IFN-γ), Interleukins (IL-10
and IL-6).
Methods: In 60 Iraqi T1DM children with recent
onset of T1DM, Lymphocyte proliferation was
analyzed using Methylthiazol tetrazolium (MTT)
assay by culturing Peripheral Blood Lymphocytes
(PBLs) with Coxsackie Virus B5 (CVB5),
Adenovirus, and Polio vaccine. Serum Interferon-γ,
IL-10 and IL-6 were quantified by sandw
The aim of this research is to know the effect of two strategies of active learning, the five fingers and traffic signals, on the first grade intermediate level student's achievement and personal intelligence. The research sample was chosen from the Al- Mansour intermediate school for boys, including (101) students divided into three groups chosen randomly which represented the first experimental group (32) students, the second experimental group (34) students, and the control group (33) students. To achieve the research aims, the research prepared a physics achievement test containing (26) items, and a personal intelligence test containing (20) items. The psychometric characteristics, of the tests were checked up the following results were
... Show More