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.
Background: Heat shock proteins have a general role in the response of the arterial wall to stress and may serve as a mediator/inducer of atherosclerosis in particular circumstances when HSPs specifically bind to the Toll-like receptor 4/CD14 complex, initiating an innate immune response, including the production of pro-inflammatory cytokines, this also followed by cytokine amplification through transmigration of macrophages and neutrophils.
Objective: To investigate the percentage of expression of HSP60 by peripheral blood lymphocyte (PBL) in atherosclerotic coronary heart disease (CHD) patients using immunocytochemistry technique.
Method: A total of fifty patient (40 males and 10 females), ranged from the mean age (59.12±8.54) y
Christianity has rituals and rituals to be carried out, and can not be abandoned, and they see that the sacred statutes ordered by Christ () his followers, including: (the mystery of baptism between Christian denominations, descriptive study) A Christian is to be baptized as the seal of faith, as evidenced by the Bible in the words of Jesus to His disciples.
Baptism takes place in the name of the Father, the Son, and the Holy Spirit. This makes them Christian through the practice of this obligatory man enters the Church, represented by the death, burial, and resurrection of Christ according to their belief. And every person who has received the sacrament of baptism remains a Christian until death, in the light of what they see.
Al-Yaqubi was biased in favor of Shia. May be du to his choice of source, materials. All historians as with other human beings are biased in their attitudes and preconceptions in one degree or another as well as in one direction or another.
The choice of source materials, their nature and the use made of them is an important index for measuring the achievement of ang historian.
Several specific questions arise. What sources did author use that were either unknown to or were not employed by his predecessors and contemporaries for whatever reason?
What sources are common to al- Yaqubi and his colleagues among the early Arab historians and what evidence of tendentiousness can be ascert- ained in these? To what extent can the author
We have studied theoretically the response of atomic three- level cascade scheme
of rubidium vapor to a strong laser under conditions in which electromagnetically
induced transparency would be induced on a weak probe beam. We show that the
medium that is an opaque to a probe laser can, by applying both lasers
simultaneously, be made transparent.
In the present work theoretical relations are derived for the efficiency evaluation for the generation of the third and the fourth harmonics u$ing crystal cascading configuration. These relations can be applied to a wide class of nonlinear optical materials. Calculations are made for beta barium borate (BBO) crystal with ruby laser /.=694.3 nm . The case study involves producing the third harmonics at X. =231.4 nm of the fundamental beam. The formula of efficiency involves many parameters, which can be changed to enhance the efficiency. The results showed that the behavior of the efficiency is not linear with the crystal length. It is found that the efficiency increases when the input power increases. 'I'he walk-off length is calculated for
... Show More• Commercial papers are one of the most important tools of the contemporary monetary market, and many of those who deal with them are ignorant of the Shariah rulings related to them, hence the urgent need to know the most prominent Sharia rulings related to commercial papers, including the discount. It is an agreement between the bank and its customer requesting the discount (the holder of the commercial paper) under which the bank is required By accelerating the value of the paper to the customer, in exchange for the latter’s obligation to transfer the ownership of the fixed right in the paper to the bank by endorsing it to him as a transfer of ownership.
• The noble Islamic Sharia does not prohibit dealing in commercial papers
The research aims to measure the impact of knowledge management processes individually and in total in the innovative marketing.
We depart search of a problem expressed in a number of intellectual and practical questions, the application of this research in the General Company for Vegetable Oil Industry, represented composed a sample of (63) (Director General and Deputy Director General and Director of the Department and the Division) in the company researched, it has been designed measuring instrument to collect the necessary data either statistical means they are the percentage and the arithmetic mean and standard deviation and coefficient of variation and the coefficient of simple correlation and model
... Show MoreA study carried out to prepare Hg1-xCdxTe compound and to see the effect on increasing the percentage of x on the compound structure by using x-ray diffraction and atomic absorption for 0
The aim of this research is to develop mechanical properties of a new aluminium-lithium-copper alloy. This alloy prepared under control atmosphere by casting in a permanent metal mould. The microstructure was examined and mechanical properties were tested before and after heat treatment to study the influence of heat treatment on its mechanical properties including; modulus of elasticity, tensile strength, impact, and fatigue. The results showed that the modulus of elasticity of the prepared alloy is higher than standard alloy about 2%. While the alloy that heat treated for 6 h and cooled in water, then showed a higher ultimate tensile stress comparing with as-cast alloy. The homogenous heat treatment gives best fatigue
... Show MorePublic relations have become vital functions in modern institutions in the complex business world. They play an important role in facilitating the process of communication between the institution and its audiences and achieve mutual understanding between the parties as public relations play this important role based on research and analysis, policy formulation and programming programs and communication with the public.
The significance of this research comes from the challenges faced by public relations in state institutions. Misunderstandings and ambiguities still plague most workers in this field, especially in defining the concept, objectives and basic functions of public rela
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