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EN
Macrophages (Mf) play an important role in induction and regulation of the immune response. It was shown previously that subcutaneous injection of hapten conjugated macrophages (TNP-Mf) induces the contact hypersensitivity (CHS) response, whereas intravenous (i.v.) or intraperitioneal administration of TNP-Mf results in unresponsiveness as a result of induced T suppressor (Ts) cells. The aim of this study was to determine if different T cell populations influence macrophages to become inducers of immunological suppression. Our findings show that indeed i.v. injection of TNP labeled macrophages isolated from control mice into syngenic recipients induces unresponsiveness. However, i.v. administration of TNP substituted macrophages isolated from TCR'-/-, TCR*-/- and $2m-/- mice induces strong CHS similar to that observed after skin painting with TNP-Cl.Moreover, it was shown that TNP conjugated macrophages isolated from CD1d-/- mice were still able to promote immunosuppression when injected intravenously. This suggests that TCR'$+ CD8+ and TCR(*+ lymphocytes stimulate macrophages to induce immunosuppression instead of a strong CHS reaction, whereas CD1d dependent NKT cells are not involved in negative regulation of macrophage function.
EN
Introduction: Experimental autoimmune encephalomyelitis (EAE) is a prototypic Th1-mediated autoimmune inflammatory disease of the central nervous system (CNS), and serves as a model for the human demyelinating disease, multiple sclerosis. Cisplatin is a drug widely used in the treatment of a variety of human neoplasias, such as advanced bladder carcinoma, adrenal cortex carcinoma, breast cancer, head and neck or lung carcinoma. Cisplatin binds to DNA and interferes with cellular repair and other mechanism, which eventually result into cell death. It is known that cisplatin can induce immunosuppressive effects through inhibition of T cell activity. Therefore we analyzed the anti-inflammatory effects of cisplatin in a rat EAE model. Materials and Methods: EAE was induced in male LEW rats by immunizing with a synthetic peptide of guinea pig myelin basic protein. The development of EAE and neurological signs were evaluated by a standard protocol. Immunohistochemistry was applied to show immune cell infiltration into the CNS. Results: Early treatment of EAE rats with cisplatin effectively ameliorated the development of disease and provided a significant protective effect compared to control rats. Further, histological analysis demonstrated that the formation of the typical perivascular cuffs and brain infiltration of monocytes and lymphocytes were complete absent in cisplatin treated rats, while abundant T cell infiltration was seen in the CNS of EAE rats. Conclusions: Our data show that cisplatin has protective effects in EAE, indicating that cisplatin could be a candidate in the treatment of human CNS autoimmunity.
EN
This article describes the results of two studies which examine the new methods of effective suppressing of stereotypic thoughts. In both studies the participants read the characteristics of the two men - one of them is mentioned as being an alcoholic - and the participants' task is to describe the typical day of both men. In the first study they began with the description of non-alcoholic buddy, in the second study, they began with the description of the alcoholic. In both experiments the mental suppression of stereotypical thoughts was manipulated. Next they were examined on recognition test of memory details about those persons. The findings of both studies showed that participants were able to suppress the stereotypical associations.
EN
In 1970, Gershon was the first to propose that T cells, in addition to their helper activity, can also play a role as regulatory cells capable of suppressing immune responses. However, the initial strong interest in T cell-mediated suppression was followed by a period of doubt and skepticism. Since the late 1990s the 'S' word started to be used in immunology again and interest in T suppressor cells has grown, ushering in a new renaissance for the field. In this article the author presents the current knowledge about a new subject called 'skin-induced tolerance'. Suppression is induced via epicutaneous immunization and is described in both Th1- and Tc1-mediated contact sensitivity reactions. The subject of skin-induced tolerance is also considered in the regulation of experimental models of autoimmune diseases such as allergic autoimmune encephalomyelitis and collagen-induced arthritis and finally in an animal model of graft rejection. The last part of this presentation will introduce the very fresh subject of ?contrasuppression', or the reversal of skin-induced suppression.
EN
In mice of the Igha immunoglobulin allotypic haplotype we found, the presence of T lymphocytes with an inherent inhibitory activity against the expression of the IgG2ab allotype (IgG2a of the Ighb immunoglobulin allotypic haplotype). This constitutive anti-IgG2ab T lymphocyte activity can be enhanced in vivo by what we called 'sensitization', which usually consists of one or two intravenous injections of B splenocytes from Ighb congenic mice. When injected at birth, the resulting anti-IgG2ab T splenocytes induce, with 100% success, total, specific and chronic (but experimentally reversible) suppression of IgG2ab in Igha/b F1 hybrid mice prepared by mating Igh congenic mice. Even if restricted to IgG2ab expression, this experimental model, which deals with an unambiguous case of T cell-mediated down-regulation of immunoglobulin production, provides a clear and powerful tool to dissect finely the behavior of the partners (T and B lymphocytes) intervening in regulation within the immune system. For example, we observed that CD4 T lymphocytes were necessary to obtain full recruitment of anti-IgG2ab CD8 T lymphocytes during the sensitization, that suppression induction in anti-IgG2ab T splenocytes of newborn recipients required cooperation between CD4 and CD8 T lymphocytes, and that CD8 T lymphocytes were essential for suppression maintenance. We showed that this suppression was not characterized by an accumulation of B lymphocytes containing the allotype they could not secrete or Cgamma2ab mRNA they could not translate. The recipient's immune system was not involved in the suppession maintenance; this was done by donor T lymphocytes, which ensured the chronicity of IgG2ab suppression throughout the recipient's life. We demonstrated that the mechanism of this suppression implied an MHC-restricted presentation by target B lymphocytes of Cgamma2ab peptides to the T cell receptor (TCR) of anti-IgG2ab T lymphocytes. Notwithstanding the requirement of a CD4-CD8 T lymphocyte cooperation during the induction phase, we functionally determined that the suppression induction implicated an MHC class I-, but not class II-restricted interaction. We also demonstrated the existence in vivo of alternative or concomitant use of perforine- and Fas-mediated cytotoxicity pathways in this T cell-induced IgG2ab suppression. Thus this suppression did not imply silencing IgG2ab production, but B lymphocyte destruction by CD8 T lymphocytes. Always using our suppression model, we demonstrated that an agonistic anti-CD40 treatment helps in recruiting CD8 cytotoxic T lymphocytes, involved in immune regulatory functions and that CD40 expression on Ighb B lymphocytes confronted with CD8 T lymphocyte effectors only operating via the Fas pathway was involved in the total suppression of IgG2ab expression. The selection and maintenance of such normal T cell activity against the IgG2ab allotype in mice of different genetic backgrounds remain somewhat enigmatic. Indeed, we did not observe any similar activity against other immunoglobulin allotypes or isotypes. The intestinal flora had no influence on the emergence of this anti-IgG2ab T lymphocyte activity, as it was untouched in germ-free Igha mice when compared with normal Igha mice. More recently, this model offered an opportunity to study problems pertaining to immune tolerance. For instance, we showed that the genetic elements involved in the building of anti-IgG2ab TCR were available in Igha and Ighb mice of different genetic backgrounds, but that somatic constraints, namely the perinatal presence of IgG2ab, effectively prevented their acquisition, while its absence led to their spontaneous emergence. Consequently, we were able to induce anti-IgG2ab T lymphocytes into a tolerance state by injecting Igha mice with soluble IgG2ab during the perinatal period. However, the full T lymphocyte tolerance obtained in this manner was not definitively acquired, as it had reversed spontaneously when investigated 3 to 6 months after the end of tolerogen treatment, even when this treatment had been prolonged from the perinatal period to 9 months of age. The mechanisms (induction and reversion) of this tolerance involves the physical elimination or the irreversible inactivation of the natural anti-IgG2ab T lymphocyte clones and their resurgence, from bone-marrow precursors, as long as the thymus remains operational, but not the establishment of a reversible, functional unresponsiveness (anergy) or an active, cell-mediated inhibition of anti-IgG2ab T clones. We attempted to elucidate, in Ighb mice, whether the natural T lymphocyte unresponsiveness to IgG2ab involved a central tolerance mechanism and to identify the type of tolerogen implicated in this tolerogenesis. The experiments principally showed that this natural T lymphocyte tolerance to IgG2ab was mediated by a thymic mechanism; that the capacity to induce it was gradually acquired by Ighb thymuses and was most probably due to potentially IgG2ab-producing/presenting cells, progressively colonizing the developing thymus; and that a significantly decreased postnatal Cgamma2ab gene transcription correlated with the emergence of anti-IgG2ab T lymphocytes in Igha/b F1 (postnatally deprived of their B lymphocyte compartment), which subjected them to autoimmune IgG2ab-allotype suppression.
EN
This article discusses the topic of suppression effects that have often been reported in recent social psycho¬logical literature. Suppression takes place when a mediating variable enhances predictive power of inde¬pendent variable on dependent variable. In this way we are able to capture with statistical analyses all sorts of theories of opponent processes that appear not only in motivation psychology but also in other areas of social psychology. Using latest social/personality psychology research examples, we describe three types of suppression effects (classical, net and cooperative) with possibilities of their use in research. At the end of the article we propose an example of suppression analysis conducted on a fictional dataset.
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