A Role for E2F1 in the Induction of ARF, p53, and Apoptosis during Thymic Negative Selection -- Zhu et al. 10 (12): 829 -- Cell...
B transgene abrogates anti-CD3-induced apoptosis in the thymus (61) . Whereas anti-CD3 can activate the TCR, antigen presentation by thymic stromal cells normally entails multiple interactions between additional cell surface molecules, such as B7/CD28, LFA-1/intercellular adhesion molecule 1, and tumor necrosis factor/TNF-R family members, that can contribute to apoptotic signaling (42 , 62, 63, 64) . Indeed, whereas TNF-R I/II-deficient mice showed impaired thymocyte apoptosis in response to anti-CD3, antigen-mediated clonal deletion was unimpaired (65) . Thus, the requirement for different players in negative selection appears to vary, depending on the nature of the recognized antigen, the MHC class, and the acute versus chronic presence of the antigen (66) . Whether deletion occurs in immature DP thymocytes in the thymic cortex or in late-stage DP and ...http://cgd.aacrjournals.org/cgi/content/full/10/12/829
The mechanism by which peripheral tolerance is induced in tumor-bearing subjects is ill defined ( 4), although findings in animal models suggest that TAA drained or carried to the lymph nodes and presented by APC in a noninflammatory context drive clonal deletion or anergy ( 37). Tolerance in 10-week-old to 11-week-old TRAMP mice ( 24) is likely induced in the absence of local inflammation because the prostate gland at that time lacks an inflammatory infiltrate and TDLN are not enlarged (data not shown). Although several previous findings were consistent with peripheral deletion of TAA-specific T cells in tumor-bearing TRAMP mice ( 24, 38), in those mice, we consistently found a population of Kb/Tag-IV+CD8+CD44+ T cells, which neither expanded in culture nor killed or produced IFN-γ upon specific stimulation, therefore implying that a sizable population of Tag-specific T cells survive peripheral ...http://cancerres.aacrjournals.org/content/68/1/292
Peripheral Deletion of Autoreactive CD8 T Cells by Cross Presentation of Self-Antigen Occurs by a Bcl-2-inhibitable Pathway...
In this work, we have shown that overexpression of Bcl-2 protects peripheral CD8 T cells from deletion in response to cross-presented self antigen. The OT-I.Eμ-Bcl-2 and OT-I.vav.Bcl-2 cells appeared similar to wild-type OT-I cells in their ability to be activated and proliferate in response to cross-presented self-antigen. If sufficiently high numbers of OT-I.Eμ-Bcl-2 T cells were transferred, they induced autoimmune diabetes (Table I). As a pro-survival molecule Bcl-2 protects lymphocytes in vitro and in vivo against apoptosis induced by growth factor deprivation, DNA damage or treatment with corticosteroids or calcium ionophores (16). For activated T cells in vivo, bcl-2 transgene expression prolongs T cell survival following injection of mice with the superantigen staphylococcus enterotoxin B (SEB; ...http://jem.rupress.org/content/196/7/947
Repression of B7.2 on Self-reactive B Cells Is Essential to Prevent Proliferation and Allow Fas-mediated Deletion by CD4+ T...
The findings here demonstrate that selectively restoring B7.2 expression on otherwise self-tolerant B cells is sufficient to switch their fate from peripheral deletion to large-scale proliferation and autoantibody secretion during interactions with specific CD4+ T cells. Of the many early signals and responses to BCR engagement that are repressed or altered in tolerant B cells ((12)-(14)), the data here single out repression of the B7.2 response as being necessary to allow peripheral tolerance by FasL/Fas-mediated clonal abortion. The findings raise interesting questions about how B7.2 switches the outcome of interactions between tolerant B and T cells, and highlight the regulation of B7.2 in B cells as a key process that may be dysregulated by inherited or acquired triggers to systemic autoimmune disease.. Three possible mechanisms may in ...http://jem.rupress.org/content/188/4/651
Transcriptional targeting of B cells for induction of peripheral CD8 T cell tolerance. | IRIS Università degli Studi di Ferrara
Several mechanisms are in place to neutralize autoimmune CD8 T cells by tolerance induction. Developing self-specific CD8 T cells are eliminated in the thymus by Ag-presenting epithelial and dendritic cells (DCs). However, CD8 T cells escaping thymic central tolerance can also be inactivated by tolerance mechanisms in peripheral organs. In contrast to DCs, the role of B cells in generating CD8 T cell tolerance is not well-characterized. To investigate this question in more detail, we transcriptionally targeted Ag to B cells using B cell-specific retroviral vectors in vivo. Although Ag expression could be detected in B cells of thymus, lymph nodes, and spleen, B cells were unable to induce central tolerance of CD8 thymocytes. In contrast, in peripheral organs, we could identify clonal deletion and functional inhibition ...https://iris.unife.it/handle/11392/471213
படியாக்கத்தேர்வு - தமிழ் விக்கிப்பீடியா
செயற்படுதல்: நோயெதிர்ப்புத் திறன் · தன்னெதிர்ப்பு (Autoimmunity) · மாற்றுநோயெதிர்ப்புத் திறன் (Alloimmunity) · ஒவ்வாமை · மிகையுணர்வூக்கம் · அழற்சி · ஊடுவினை (Cross-reactivity) · செயற்படாமை: நோயெதிர்ப்புப் பொறுதி · மையப் பொறுதி (Central tolerance) · புற பொறுதி (Peripheral tolerance) · படியாக்க வலுவிழப்பு (Clonal anergy) · படியாக்க நீக்கம் (Clonal deletion) · கர்ப்பத்தில் நோயெதிர்ப்புப் பொறுதி (Immune tolerance in pregnancy) · நோயெதிர்ப்புக் குறைபாடு (Immunodeficiency) · ...https://ta.wikipedia.org/wiki/%E0%AE%AA%E0%AE%9F%E0%AE%BF%E0%AE%AF%E0%AE%BE%E0%AE%95%E0%AF%8D%E0%AE%95%E0%AE%A4%E0%AF%8D%E0%AE%A4%E0%AF%87%E0%AE%B0%E0%AF%8D%E0%AE%B5%E0%AF%81
The lack of NF-kappa B transactivation and PKC epsilon expression in CD4(+)CD8(+) thymocytes correlates with negative selection...
Deletion of autoreactive thymocytes at the DP stage is the basis for tolerance to thymus-expressed self antigens. In this study we investigated whether distinct signalling pathways are induced in DP thymocytes as compared to mature T cells upon stimulation with antigen. Using triple transgenic mice expressing a TCR transgene, dominant negative ras/Mek proteins and a reporter gene construct with AP-1 or NF-kappa B binding sites, we showed a complete lack of transcriptional activity of NF-kappa B but not AP-1 in DP thymocytes, whereas both were transcriptionally active in mature T cells after antigenic stimulation. Lack of NF-kappa B induction correlated with increased death in response to antigen. AP-1 induction was dependent on the integrity of the ras/Mek pathway indicating that this pathway was activated in the DP thymocytes. In contrast, we found a complete lack of ...https://www.ndorms.ox.ac.uk/publications/2783
Central Tolerance Regions and Reference Regions for Some Normal Populations :: UMBC Electronic Theses and Dissertations
A reference interval represents a range of values that a physician can use in order to interpret a single test result from a patient. A 95% reference interval is simply the interval from the 2.5th to the 97.5th percentiles of the distribution of the test result. Since such an interval will typically depend on unknown parameters, we can use a random sample to compute an interval that will contain the reference interval with a specified confidence level. The interval so computed is referred to as a central tolerance interval. A central tolerance interval captures, with a given confidence level, a specified percentage of the central part of a univariate population. Reference regions and central tolerance regions are similarly defined for a multivariate population. This thesis considers the problem of deriving central tolerance intervals and regions for some normal populations, including multivariate normal distribution, multivariate linear regression model and the one-way and two-way random models. ...http://contentdm.ad.umbc.edu/cdm/singleitem/collection/ETD/id/24554/rec/10
There is clear evidence that tumor patients are able to generate TAA-specific T cell immunity spontaneously. Whereas the presence of tumor-specific T cells has been shown by many groups and for various tumor types, much less is known about the function of TAA-specific T cells in vivo. Most of the TAAs including differentiation, germ-line, and shared overexpressed antigens are not tumor specific but are also expressed at low levels in certain nonmalignant tissues. This should influence the type of T cell response because deletion of functional high-avidity self-reactive T cells in the thymus as well as peripheral deletion or anergy was shown in various animal models (reviewed in Ref. 74 ). There are a few recent studies analyzing the functional avidity of TAA-specific T cells in patients. In leukemia patients, low-avidity T cells to proteinase 3, which are ...http://clincancerres.aacrjournals.org/content/9/12/4296
Studies using the 4.1 TCR transgenic system found thymic or peripheral deletion as well as anergy and ignorance do not contribute to CD4 T-cell tolerance induction in NOR mice (13). Similarly, we found the frequency and proliferative capacity of BDC2.5-like CD4 T-cells was comparable in NOD and NOR mice. The fact that NOR CD4 T-cells induced type 1 diabetes in some NOD.CD4null recipients revealed the retention of at least minimal pathogenic activity. On the other hand, NOR T-cells are more susceptible than those from NOD mice to activation-induced cell death (AICD) (34). Therefore, abortive activation followed by AICD may limit the effector function of NOR diabetogenic CD4 T-cells. Another nonmutually exclusive possibility is that diabetogenic CD4 T-cells are more efficiently suppressed in NOR than NOD mice. However, we found no difference in the frequency or in vitro suppressive function between NOD and NOR ...http://diabetes.diabetesjournals.org/content/57/12/3273
Fas and Fas ligand in embryos and adult mice: ligand expression in several immune-privileged tissues and coexpression in adult...
The cell surface receptor Fas (FasR, Apo-1, CD95) and its ligand (FasL) are mediators of apoptosis that have been shown to be implicated in the peripheral deletion of autoimmune cells, activation-induced T cell death, and one of the two major cytolytic pathways mediated by CD8+ cytolytic T cells. To gain further understanding of the Fas system., we have analyzed Fas and FasL expression during mouse development and in adult tissues. In developing mouse embryos, from 16.5 d onwards, Fas mRNA is detectable in distinct cell types of the developing sinus, thymus, lung, and liver, whereas FasL expression is restricted to submaxillary gland epithelial cells and the developing nervous system. Significant Fas and FasL expression were observed in several nonlymphoid cell types during embryogenesis, and generally Fas and FasL expression were not localized to characteristic sites of programmed cell death. In the adult mouse, RNase ...http://jcb.rupress.org/content/133/2/335
Clonal Deletion Theory of Immunity | NutritionFacts.org
Plant-based diets may be protective against multiple sclerosis because IGF-1 can prevent our immune system from eliminating autoimmune cells.https://nutritionfacts.org/video/clonal-deletion-theory-of-immunity/
clonal deletion - oi
In Vivo Imaging of an Inducible Oncogenic Tumor Antigen Visualizes Tumor Progression and Predicts CTL Tolerance | The Journal...
We described Tg mice, which express a transforming fusion protein, consisting of SV40 large T Ag and luciferase, after site-specific Cre-LoxP recombination. This strategy allowed direct visualization of oncogene expression and noninvasive imaging of tumor growth in a spatiotemporal manner. Surprisingly, in mice of all LoxP-TagLuc-pA founder lines, a ubiquitous and Cre recombination-independent expression of the TagLuc gene was detected by BLI. This leakiness might have resulted from a bicistronic mRNA due to reading through the polyA signal 3′ of the stop cassette. Consequently, CTLs in LoxP-TagLuc-pA mice were tolerant toward the dominant Tag epitope. Because BLI detected Cre recombination-independent TagLuc expression in the thymus, T cell deletion by central tolerance is likely (34). LoxP-TagLuc mice that lacked the polyA signal sequence 3′ of the TagLuc gene showed on average a 10-fold lower Cre recombination-independent TagLuc expression. Because the two transgene DNA constructs ...http://www.jimmunol.org/content/184/6/2930.long
Alpha Omega Alpha - 2010 Research Abstract
Mentor: Nina Luning Prak, MD, PhD, University of Pennsylvania School of Medicine. Aberrant light chain rearrangement has been implicated in the loss of tolerance in self-reactive B cells. Ongoing light chain rearrangement, a process termed receptor editing, is a major mechanism for tolerizing self-reactive B cells. We have observed that highly edited B cells become less frequent once fully assembled antibody molecules are expressed on the B cell surface. We hypothesized that the decrease in highly edited B cells is due either to negative selection (death of cells that have failed to edit successfully), positive selection of cells with fewer rearrangements or escape of edited B cells to a hitherto unidentified peripheral compartment. Here, we report preliminary data from a pilot experiment that macrophages may be involved in the selective depletion of highly edited B cells. ...http://alphaomegaalpha.org/student_research_abstract_li.html
Continuous inhibitory signaling by both SHP-1 and SHIP-1 pathways is required to maintain unresponsiveness of anergic B cells |...
Induction and maintenance of unresponsiveness of B cells that recognize low valency autoantigens presents a challenging biological problem. Such antigens, even if they have high affinity for the BCR, are likely to induce relative weak signals because they do not aggregate receptors efficiently. Available evidence suggests that when autoantigen avidity and, consequently, ability to induce signaling is not sufficient to induce editing or clonal deletion, autoreactive B cells may be rendered anergic. Chronic stimulation by such antigens leads to changes in intracellular signaling circuitry that makes the cell unresponsive to a variety of signals, including aggregation of previously unoccupied BCR. This unresponsiveness is not durable, as would be expected if it were mediated by genetic reprogramming. Removal of autoantigen from BCR can lead to restoration of ...http://jem.rupress.org/content/early/2016/04/19/jem.20150537
Dear Immunonetters, I would like to bring another player into the Self/non-self discrimination arena. That Being the effect of Anergic T-cells on other autoreactive T-cells.This concept has been discussed in the papers by Lasalle and Hafler ( FASEB J. 8:601-608 1994) and Lombardi et al ( science 264:1587 1994). I agree with the authors that the Anergic T-cells play an important rolein self/nonself discrimination. In summary this is what's happening. The Thymus, site of clonal deletion, is very efficient in removing autoreactive T-cells. But nothing is perfect and some autoreactive cells escape this screening. These T-cells can be safely present in the periphery if the antigens they are reactive to are hidden away from them or not presented to them. This is called Clonal Ignorance. If MHC/AG is presented to the autoreactive T-cell but is not ...http://www.bio.net/bionet/mm/immuno/1994-July/001736.html
An Overview of the Immune System
Figure 10. Killer T-cells eliminate intracellular pathogens. Intracellular pathogens are eliminated by a specialized type of lymphocyte, called a killer T-cell (see figure 10. Killer T-cells are a subclass of T-cells, meaning that they mature in the thymus, are tolerized via clonal deletion, and do not hypermutate when cloning. Killer T-cells bind not to simple proteins, but to proteins held by MHC molecules. In other words, killer T-cells can only recognize proteins expressed by MHC on the surface of host cells. If a killer T-cell is activated by recognition of a MHC/protein combination, it will kill the infected host cell. There are many ways in which this is done, e.g. killer T-cells can punch holes in cell walls, or secrete chemicals that destroy cell walls, etc. NEXT: Summary ...http://www.cs.unm.edu/~immsec/html-imm/intracellular.html
The importance of T regulatory cells in tolerance to NPI xenografts induced by the combined mAb therapy was demonstrated when tolerant B6 mice became diabetic after depletion of CD25+ cells using mAb. We found no significant difference in the total number of spleen cells and percentage of CD4+, CD8+ T-cells as well as B-cells from tolerant B6 mice compared with naïve B6 mice, suggesting that tolerance due to clonal deletion is unlikely. However, further analysis of the phenotype of immune cells from tolerant B6 mice using flow cytometry showed a higher percentage of CD4+ T-cells, co-expressing cell surface markers for T regulatory cells (13-18) compared with those observed in naïve B6 mice.. We also showed that T-cells from tolerant B6 mice did not proliferate after stimulation with porcine spleen ...http://diabetes.diabetesjournals.org/content/59/4/958.full
The importance of T regulatory cells in tolerance to NPI xenografts induced by the combined mAb therapy was demonstrated when tolerant B6 mice became diabetic after depletion of CD25+ cells using mAb. We found no significant difference in the total number of spleen cells and percentage of CD4+, CD8+ T-cells as well as B-cells from tolerant B6 mice compared with naïve B6 mice, suggesting that tolerance due to clonal deletion is unlikely. However, further analysis of the phenotype of immune cells from tolerant B6 mice using flow cytometry showed a higher percentage of CD4+ T-cells, co-expressing cell surface markers for T regulatory cells (13-18) compared with those observed in naïve B6 mice.. We also showed that T-cells from tolerant B6 mice did not proliferate after stimulation with porcine spleen ...http://diabetes.diabetesjournals.org/content/59/4/958
The genetic basis of negative selection of Tcrb-Vll+ T cells | SpringerLink
Non- H-2 genes responsible for negative selection of Tcrb-V 11+ T cells were examined using backcross mice of various strains with C58, which does not delete Tcrb-V 11+ T cells. Two independently segrhttps://link.springer.com/article/10.1007%2FBF01719234
Update on Staphylococcal Superantigen-Induced Signaling Pathways and Therapeutic Interventions - pdf descargar
Update on Staphylococcal Superantigen-Induced Signaling Pathways and Therapeutic Interventions. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.http://libros.duhnnae.com/2017/jun6/149762094333-Update-on-Staphylococcal-Superantigen-Induced-Signaling-Pathways-and-Therapeutic-Interventions.php
Yamaha VETO 40 Help please! - Page 2 - RIBnet Forums
If your not confident, buythe parts and bring it to Leeds, I will do it for you. It would be most of the day. If not here goes. 1) you have to be sure that's the problem. 2) How many hours has thehttp://www.rib.net/forum/f36/yamaha-veto-40-help-please-66376-2.html
The Role of Mammalian Actin Binding Protein 1 in Coupling BCR Signaling and Antigen Transport Functions
The B cell receptor (BCR) serves as both signal-transducer and antigen-transporter. Binding of antigens to the BCR induces signaling cascades and antigen-processing and presentation, two essential cellular events for B cell activation. BCR-initiated signaling increases BCR-mediated antigen-processing efficiency by increasing the rate and specificity of antigen transport. Previous studies showed a critical role for the actin cytoskeleton in these two processes. Here I found that actin-binding protein 1 (Abp1/HIP-55/SH3P7) functioned as an actin-binding adaptor protein, coupling BCR signaling and antigen-processing pathways with the actin cytoskeleton. Gene knockout of Abp1 and over-expression of the SH3 domain of Abp1 inhibited BCR-mediated antigen internalization, consequently reducing the rate of antigen transport to processing compartments and the efficiency of ...http://drum.lib.umd.edu/handle/1903/8122