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.
Educational of the mind is a weapon to a different knowledges which
benefit in ife and developed the mind in many field and practice him in a
regular form in a right thinking and practice sense on exactly recognizing and
conception things which is senses and regulating the memory and providing
with benefit information which fit to minded of person,the present research
aimed at answering the following two questions:
1-Does the concept of mind differ with age?
2-Does the recognition on function of mind developed with development of
age?
The research population consisted of the children in the primary schools
of Baghdad/center,and the students of the Education for woman
college/Baghdad university for the age
Brainstorming is one of the fundamental and necessary concepts for practicing the auditing profession, as auditing standards encouraged the implementation of brainstorming sessions to reach reasonable assurance about the validity of the evidence and information obtained by the auditor to detect fraud, as the implementation of brainstorming sessions and the practice of professional suspicion during the audit process lead to increase the quality of auditing and thus raise the financial community's confidence in the auditing profession again after it was exposed to several crises that led to the financial community losing confidence in the auditing profession.
The research aims to explain the effect of brain
... Show MoreBrainstorming is one of the fundamental and necessary concepts for practising the auditing profession, as auditing standards encouraged the implementation of brainstorming sessions to reach reasonable assurance about the validity of the evidence and information obtained by the auditor to detect fraud, as the implementation of brainstorming sessions and the practice of professional suspicion during the audit process lead To increase the quality of auditing and thus raise the financial community's confidence in the auditing profession again after it was exposed to several crises that led to the financial community losing confidence in the auditing profession.
The research aims to explain the effect of brain
... Show MoreAbstract Objective: The study aimed to assess the factors contributes of patient with bladder cancer and to find out the relationship between the factors of bladder cancer with certain variable. Methodology: A descriptive study to assessment of factors that contribute to bladder cancer that was carried out Al-Karama teaching hospital, Al-Kendy teaching hospital, Specialty Surgery teaching hospital and Al-Yarmok teaching hospital for the period of November 2003 to August 2004. A purposive (non-probability) sample of (100) patients with bladder cancer. An assessment from was constructed for the purpose of the st
The scholars of Arabic - may God reward them with the reward of the doers of good - laid down the rules of this language, the cycle of which never ceases to dazzle minds, so they adopted principles according to which they judged the denomination of this word, and the accusative of that, and determined in its light the worker and the done, until they reached us the rules and foundations of our dear language, and it is obvious that they differ. The origins of grammarians from one school of thought to another, or from one world to another, especially with regard to the subsidiary rules, and this difference was clearly reflected in what we have received from the rules, as we find a difference in the rulings that they restricted to the one fa
... Show MoreThe field of climatic geography focuses on the study of the Earth's surrounding atmosphere, particularly the lower (surface) part close to the Earth's surface. This field examines the interactions within the atmosphere resulting from the solar radiation that reaches the Earth and the subsequent distribution of atmospheric pressure. Consequently, certain surface pressure systems, both high and low, emerge and vary in their temporal and spatial impacts on the climate of the Arabian Peninsula. Therefore, it is essential to conduct a comprehensive and detailed study to understand the causes, development, movement, geographical distribution, and monthly and seasonal recurrence of these pressure systems. For this purpose, a minor climatic
... Show MoreContemporary residential neighborhoods suffer from weak sustainability of urban residential environments as a result of the adoption of inefficient spatial organization at the neighborhood unit level. This resulted negative characteristics which affected the achievement of sustainable development plans for the residential environment that constitute the majority of the urban fabric of cities.
The physical affordances ,within the vocabulary of recent times,overcame the spiritual ones and affected the residential environment. Accordingly,the concept of space changed in contemporary residential areas through the dominance of the physical aspect (mass) on the symbolic aspect (space).The modern technology occupied an important level b
... Show MoreInterferon’s plays a role in innate immune responses through upregulation of costimulatory molecules and induction of proinflammatory cytokines. Interferon alpha (IFN α) type of Interferons. The present study characterized IFNα cDNA . The interferon’s play a great role in protection from infections, caused by microorganisms, and have powerful antiproliferative and immunomodulation activity. In this study DNA was isolated from bovine blood leukocyte, which was used in the quality of matrix for amplification of α-interferon gene with the use of PCR, and isolation of gene α-interferon and transformation in vector pUC18 and expression vector pET24b (+). All plasmids contained an additional DNA fragment size corresponding to the gene
... Show MoreBackground: Adipose derived-mesenchymal stem cells have been used as an alternative to bone marrow cells in this study. Objective: We investigated the in vitro isolation, identification, and differentiation of stem cells into neuron cells, in order to produce neuron cells via cell culture, which would be useful in nerve injury treatment. Method: Mouse adipose mesenchymal stem cells were dissected from the abdominal subcutaneous region. Neural differentiation was induced using β-mercaptoethanol. This study included two different neural stage markers, i.e. nestin and neurofilament light-chain, to detect immature and mature neurons, respectively. Results: The immunocytochemistry results showed that the use of β-mercaptoethanol resulted in
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