The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc.
A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.
Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL.
Lymphotoxin beta Receptor
A member of the tumor necrosis factor receptor superfamily. It has specificity for LYMPHOTOXIN ALPHA1, BETA2 HETEROTRIMER and TUMOR NECROSIS FACTOR LIGAND SUPERFAMILY MEMBER 14. The receptor plays a role in regulating lymphoid ORGANOGENESIS and the differentiation of certain subsets of NATURAL KILLER T-CELLS. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
Autoimmune diseases affecting multiple endocrine organs. Type I is characterized by childhood onset and chronic mucocutaneous candidiasis (CANDIDIASIS, CHRONIC MUCOCUTANEOUS), while type II exhibits any combination of adrenal insufficiency (ADDISON'S DISEASE), lymphocytic thyroiditis (THYROIDITIS, AUTOIMMUNE;), HYPOPARATHYROIDISM; and gonadal failure. In both types organ-specific ANTIBODIES against a variety of ENDOCRINE GLANDS have been detected. The type II syndrome differs from type I in that it is associated with HLA-A1 and B8 haplotypes, onset is usually in adulthood, and candidiasis is not present.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
Mice, Inbred NOD
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.
Glucose Tolerance Test
A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.
Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).
A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.
Receptors, Antigen, T-Cell
Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Bone Marrow Transplantation
Hematopoietic Stem Cell Transplantation
Transfer of HEMATOPOIETIC STEM CELLS from BONE MARROW or BLOOD between individuals within the same species (TRANSPLANTATION, HOMOLOGOUS) or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). Hematopoietic stem cell transplantation has been used as an alternative to BONE MARROW TRANSPLANTATION in the treatment of a variety of neoplasms.
Muscular Dystrophy, Duchenne
An X-linked recessive muscle disease caused by an inability to synthesize DYSTROPHIN, which is involved with maintaining the integrity of the sarcolemma. Muscle fibers undergo a process that features degeneration and regeneration. Clinical manifestations include proximal weakness in the first few years of life, pseudohypertrophy, cardiomyopathy (see MYOCARDIAL DISEASES), and an increased incidence of impaired mentation. Becker muscular dystrophy is a closely related condition featuring a later onset of disease (usually adolescence) and a slowly progressive course. (Adams et al., Principles of Neurology, 6th ed, p1415)
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
A pathological state in which BLOOD GLUCOSE level is less than approximately 140 mg/100 ml of PLASMA at fasting, and above approximately 200 mg/100 ml plasma at 30-, 60-, or 90-minute during a GLUCOSE TOLERANCE TEST. This condition is seen frequently in DIABETES MELLITUS, but also occurs with other diseases and MALNUTRITION.
Granulocyte-Macrophage Colony-Stimulating Factor
An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages.
Specific Pathogen-Free Organisms
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
Negative selection by IgM superantigen defines a B cell central tolerance compartment and reveals mutations allowing escape. (1/8)(+info)
Complete diabetes protection despite delayed thymic tolerance in NOD8.3 TCR transgenic mice due to antigen-induced extrathymic deletion of T cells. (2/8)(+info)
Unmodified histone H3K4 and DNA-dependent protein kinase recruit autoimmune regulator to target genes. (3/8)(+info)
Role of impaired central tolerance to alpha-myosin in inflammatory heart disease. (4/8)(+info)
Macroautophagy substrates are loaded onto MHC class II of medullary thymic epithelial cells for central tolerance. (5/8)(+info)
Thymus-homing dendritic cells in central tolerance. (6/8)(+info)
Characterization of human thymic exosomes. (7/8)(+info)
CVID-associated TACI mutations affect autoreactive B cell selection and activation. (8/8)(+info)
Unmodified Histone Proteins | EpiGentek
Unmodified histone proteins such as H3 and H4 are useful for studying epigenetic mechanisms such as histone methylation, histone acetylation, and histone phosphorylation, which occur as a result of the modification to histone...
Induction of Central Tolerance - Muscular Dystrophy - Fitness VIP
The induction of hematopoietic mixed chimerism, defined as the coexistence of donor and recipient hematopoietic cells, could be an approach to induce robust central tolerance. This strategy capitalizes on the use of nonmyeloablative hematopoietic stem cell transplantation (HSCT) prior to injection of myogenic stem cells from the donor HST (Parker et al. 2008). In this study two irradiated GRMD dogs with established full or partial chimerism first achieved at 11-26 months, were injected with donor-specific muscle-derived cells. The recipient dogs were transiently immunosuppressed with cyclosporine for 40 days. Local dystro-phin expression, up to 6.5% of normal levels, was sustained for periods up to 24 months post injection. This strategy is promising, as novel developments in the area of nonmyeloablative HSCT are ongoing for other cell-based therapies for benign diseases. Induction of central tolerance by intrathymic injection of viral vectors has been tested in rodents, and offers alternatives ...
MLLT10 - Protein AF-10 - Homo sapiens (Human) - MLLT10 gene & protein
Probably involved in transcriptional regulation. In vitro or as fusion protein with KMT2A/MLL1 has transactivation activity. Binds to cruciform DNA. In cells, binding to unmodified histone H3 regulates DOT1L functions including histone H3 Lys-79 dimethylation (H3K79me2) and gene activation (PubMed:26439302).
Generation of hematopoietic chimerism and induction of central tolerance - GREINER DALE L.
The invention relates to the methods for producing hematopoietic chimerism and central tolerance by peripheral tolerance induction without myeloablative conditioning.
The contribution of GPCRs to thymocyte medullary entry and central tolerance - Lauren Ehrlich
In this project we propose to determine the role of candidate G protein-coupled receptors (GPCRs) in enforcing deletion of developing auto-reactive T cells in t...
Most human cancers acquire tens to hundreds of somatic mutations (termed the tumor mutome) during their development (1). Each of these mutations has the potential to generate one or more novel T-cell antigens (termed neoepitopes) uniquely specific to each individual patients tumor. Because these neoepitopes are not present in the germline, and are not encountered until after the onset of oncogenesis, repertoires of high-avidity T cells capable of recognizing them may avoid central tolerance and escape deletion in the thymus. For these reasons, numerous investigators have proposed that the tumor mutome provides an attractive source of antigenic targets for developing patient-specific tumor vaccines (2-5).. Because it is already possible to rapidly and comprehensively identify tumor mutations using next-generation DNA- and RNA-sequencing technologies (1), the first technical hurdle for the development of this approach has been overcome. However, it may not be practical to target the full ...
Science Signaling Podcast: 26 June 2012 | Science Signaling
This Podcast features an interview with Vassiliki Boussiotis, senior author of a Research Article published in the 26 June 2012 issue of Science Signaling. Boussiotis discusses her groups investigation of a molecular mechanism by which autoreactive T cells are suppressed in the periphery. Most autoreactive T cells are eliminated by mechanisms of central tolerance in the bone marrow or thymus before they enter the circulation. Autoreactive T cells that escape central tolerance are suppressed or eliminated by mechanisms of peripheral tolerance. Boussiotiss group has described a molecular chain of events downstream of the receptor programmed death-1 (PD-1) that inhibit proliferation of autoreactive T cells.. ...
Trial watch: chemotherapy-induced immunogenic cell death in immuno-oncology. | Sotio
The term immunogenic cell death (ICD) denotes an immunologically unique type of regulated cell death that enables, rather than suppresses, T cell-driven immune responses that are specific for antigens derived from the dying cells. The ability of ICD to elicit adaptive immunity heavily relies on the immunogenicity of dying cells, implying that such cells must encode and present antigens not covered by central tolerance (antigenicity), and deliver immunostimulatory molecules such as damage-associated molecular patterns and cytokines (adjuvanticity). Moreover, the host immune system must be equipped to detect the antigenicity and adjuvanticity of dying cells. As cancer (but not normal) cells express several antigens not covered by central tolerance, they can be driven into ICD by some therapeutic agents, including (but not limited to) chemotherapeutics of the anthracycline family, oxaliplatin and bortezomib, as well as radiation therapy. In this Trial Watch, we describe current trends in the ...
Neoantigen Vaccine Generates Intratumoral T Cell Responses in Phase Ib Glioblastoma Trial
Neoantigens, which are derived from tumour-specific protein-coding mutations, are exempt from central tolerance, can generate robust immune responses and can function as bona fide antigens that facilitate tumour rejection.
Immune tolerance - Wikipedia
Immune tolerance, or immunological tolerance, or immunotolerance, is a state of unresponsiveness of the immune system to substances or tissue that have the capacity to elicit an immune response in given organism. It contrasts with conventional immune-mediated elimination of foreign antigens (see Immune response). Tolerance is classified into central tolerance or peripheral tolerance depending on where the state is originally induced-in the thymus and bone marrow (central) or in other tissues and lymph nodes (peripheral). The mechanisms by which these forms of tolerance are established are distinct, but the resulting effect is similar. Immune tolerance is important for normal physiology. Central tolerance is the main way the immune system learns to discriminate self from non-self. Peripheral tolerance is key to preventing over-reactivity of the immune system to various environmental entities (allergens, gut microbes, etc.). Deficits in central or peripheral tolerance also cause autoimmune ...
Case Studies in Immunology (13) CVID TACI mutation 40 yo F w/ recurrent respiratory and GI infections Lower than normal levels...
(14) X-Linked SCID IL-2Rγ mutation 6 mo M has thrush, RSV, Pseudomonas aeruginosa No T-cells, low Ig levels Normal B-cell count, did not react to IL-2Rγ Unresponsive to PHA, ConA, PWM, immunizations Complete non-random X- chromosome inactivation Tx: IVIg, ribavirin, TMP-STX, maternal marrow graft SCID: Thrush, persistent cough, intractable diarrhea X-linked is different because B-cell count is normal Mutation in IL-2Rγ (Xq11) is also part of IL-7 involved in T-cell development Successful bone marrow graft yields normal life with Ig-therapy
Thymic epithelial cells control let-7 up-regulation in thymic B progenitors during the neonatal to adult transition | The...
The postnatal thymus is an efficient microenvironment for T cell specification and differentiation. B cells are also present in the thymus, and have been recently implicated in the central tolerance. In Foxn1lacZmutant mice, which undergo premature thymic involution beginning 1 week after birth, T committed progenitors were progressively reduced, however, thymic B cells started to increase at 1 week and transiently formed a peak at 3-4 weeks. These increased B cells were developed from neonatal derived BM progenitors possessing a high B potential, were originally generated in the thymus. Most of them showed CD19loB220loCD24hiCD43+/−IgM−progenitor phenotype with increased expression of Ly51 but decrease of CD25 accumulating at pre-B-II stage. These B progenitors showed a delayed down-regulation of Lin28b, an impaired up-regulation of Let-7 with an increased expression of Arid3a. However the treatment of these progenitor B cells with Vitamin D3 might up-regulate Let-7 and down-regulate Arid3 ...
Identification of a novel post-translationally modified antigen in the NOD mouse model of autoimmune diabetes
Autoimmunity arises from a failure of the immune system to establish or maintain self-tolerance. In the thymus, developing T cells are exposed to self-peptides derived from genetically encoded proteins, and self-reactive T cells are either deleted or develop a regulatory phenotype before venturing into the periphery. Post-translational modification (PTM) of self-peptides in the periphery may lead to the generation of neo-epitopes that are not displayed in the thymus. T cells specific for these modified peptides can bypass central tolerance mechanisms and escape into the periphery where they may ...
Controle Pós-Transcricional do Gene Autoimmune Regulator (Aire) por meio do micr...
O timo é um órgão linfoide primário onde ocorre o estabelecimento da tolerância imunológica central pela eliminação de clones de linfócitos T auto reativos. Precursores de linfócitos T adentram o timo...
Mechanisms of intrathymic tolerance induction to isolated rat hepatocyte allografts - Attavar - 2003 - Hepatology - Wiley...
Ilan Y, Attavar P, Takahashi M, Davidson A, Horwitz M, Guida J, Chowdhury N Roy, Chowdhury J. Roy Induction of central tolerance by intrathymic inoculation of adenoviral antigens into the host thymus permits long-term gene therapy in Gunn rats. J Clin Invest 1996; 98: 2640-2647 ...
John J. Lee, MD | Boston Childrens Hospital
Lee JJ, Rauter I, Garibyan L, Ozcan E, Sannikova T, Dillon SR, Cruz AC, Siegel RM, Bram R, Jabara H, Geha RS. The murine equivalent of the A181E TACI mutation associated with common variable immunodeficiency severely impairs B-cell function. Blood. 2009 Sep 10; 114(11):2254-62. View abstract ...
JCI Insight - Combination central tolerance and peripheral checkpoint blockade unleashes antimelanoma immunity
Mice. C57BL/6 AireGW/+ mice (17) and C57BL/6 AireGW/+ TRP-1 TCR Tg RAG−/− mice (11) were housed and bred in sterile, specific pathogen-free mouse facilities at the University of North Carolina at Chapel Hill and UCSF. C57BL/6 Aire WT littermate controls were used in all experiments. RAG1−/− mice were purchased from the Jackson Laboratory.. Antibodies and flow cytometry. Anti-CD4 (clone RM4-5), anti-CD3 (clone 145-2c11), anti-Ki67 (clone SolA15), anti-KLRG1 (clone 2F1), anti- granzyme B (clone NGZB), anti-FOXP3 (clone FJK-16s), and anti-CD25 (clone PC61.5) antibodies were purchased from eBioscience. Anti-CD8a (clone 5H10) antibody was purchased from Invitrogen. Intracellular staining for cytokines and FOXP3 were performed as in ref. 11. All samples were run on a Dako CyAn flow cytometer (Beckman-Coulter) and analyzed using FlowJo (TreeStar Inc.).. Isolation of TILs. TILs were isolated as previously described (11). Tumors were dissected and minced before incubation with collagenase type ...
Future of Chimeric Antigen Receptors (Cars): Could it Drive Solutions Beyond Cancer? Examples in Autoimmune Diseases
Promising data from trials investigating T/NK-cells modified to express CARs against tumour antigens have generated extensive interest from clinicians, researchers and pharmaceutical companies, leading to broaden the applications of CARs beyond cancer through other pathologies, as autoimmune diseases or allograft rejection [13,14]. Autoimmunity can be broadly separated in two processes: via self-reactive antibodies or autoantibodies (produced by plasma cells from the B lymphocyte lineage), and/or via self-reactive T-lymphocytes. This may occur during the processes of selection of those cells during their development (central tolerance), in which negative selection to self-antigens fails, or due to changes in target tissues (break of peripheral tolerance). Between these peripheral autoimmune mechanisms, there are the autorreactivitiy against the so-called sequestered antigens (self-antigens present in isolated areas of the organism that are not exposed in normal conditions), that become ...
Conformational Melding Permits a Conserved Binding Geometry in TCR Recognition of Foreign and Self Molecular Mimics | The...
T cell receptor recognition of peptide Ags presented by class I or class II MHC proteins is a cornerstone of cellular immunity. Recognition of foreign Ags forms the basis for defense against viruses and other pathogens, yet recognition of self Ags can lead to autoimmunity. Although the central tolerance mechanism of negative selection plays a protective role against autoimmunity, the high level of cross-reactivity present within the T cell repertoire can promote autoimmunity if T cells are activated by foreign Ags that share key structural or chemical features with self Ags. This concept of molecular mimicry has been implicated in a number of autoimmune pathologies, including type 1 diabetes, lupus, and multiple sclerosis (1-3).. Previously determined structures of TCRs in complex with self Ags associated with autoimmunity have shown deviations from the binding mode traditionally seen in TCR recognition of foreign Ags. The traditional binding mode, typified by the structure of the αβ A6 TCR ...
PDF] Autonomous role of medullary thymic epithelial cells in central CD4+ T cell tolerance | Semantic Scholar
Medullary thymic epithelial cells (mTECs) serve an essential function in central tolerance by expressing peripheral-tissue antigens. These antigens may be transferred to and presented by dendritic cells (DCs). Therefore, it is unclear whether mTECs, in addition to being an antigen reservoir, also serve a mandatory function as antigen-presenting cells. Here we diminished major histocompatibility complex (MHC) class II on mTECs through transgenic expression of a designer microRNA specific for the MHC class II transactivator CIITA (called C2TA here). This resulted in an enlarged polyclonal CD4+ single-positive compartment and, among thymocytes specific for model antigens expressed in mTECs, enhanced selection of regulatory T cells (Treg cells) at the expense of deletion. Our data document an autonomous contribution of mTECs to both dominant and recessive mechanisms of CD4+ T cell tolerance and support an avidity model of Treg cell development versus deletion.
Ex-vivo expanded DC induce donor-specific central and peripheral tolerance and prolong the acceptance of donor skin allografts
Dendritic cells (DCs) are known to regulate immune responses by inducing both central and peripheral tolerance. DCs play a vital role in negative selection of developing thymocytes by deleting T cells with high-affinity for self-peptide-major histocompatibility complexes. In the periphery, DCs mediate peripheral tolerance by promoting regulatory T-cell development, induction of T-cell unresponsiveness, and deletion of activated T cells. We studied whether allogeneic DCs, obtained from bone marrow cultured with either Flt3L (FLDCs) or granulocyte-macrophage colony-stimulating factor (GMDCs), could induce allospecific central and peripheral tolerance after IV injection; B cells were used as a control. The results showed that only FLDCs reached the thymus after injection and that these cells induced both central and peripheral tolerance to donor major histocompatibility complexes. For central tolerance, injection of FLDCs induced antigen-specific clonal deletion of both CD8 and CD4 single-positive
Advanced testicular germ cells, expressing novel cell surface area and intracellular
Advanced testicular germ cells, expressing novel cell surface area and intracellular proteins, show up following the establishment of central tolerance and so are auto-immunogenic so. myoid cells, additional expands its program to review testis morphogenesis. We will also discuss the potential use of this model to study the effects of drugs/environmental toxins on testis morphogenesis, tight junction formation and SCCmyoid cell interactions. , co-grafted allogeneic pancreatic islets with syngeneic or allogeneic SC-enriched fractions underneath the kidney capsule of INCB8761 supplier diabetic rats. In this study, 65% of the co-grafted animals remained normoglycemic for over 100 days, while none of the animals receiving islets alone became normoglycemic. However, a short course of immune suppression (cyclosporine for 3 days) was INCB8761 supplier required for the SCs to prolong survival of allogeneic islets. Korbutt , extended these results by modifying the SC isolation method and adding a ...
Nemazee D (2006). "Receptor editing in lymphocyte development and central tolerance". Nat Rev Immunol. 6 (10): 728-740. doi: ...
Therefore, one of the most important roles of the thymus is the induction of central tolerance. The thymus is largest and most ... One of the primary functions of the thymus is to prevent autoimmunity through the process of central tolerance, immunologic ... The random nature of the genetic rearrangement results in a requirement of central tolerance mechanisms to remove or inactivate ... Peterson, P. R.; Org, T. N.; Rebane, A. (2008). "Transcriptional regulation by AIRE: Molecular mechanisms of central tolerance ...
Limfocyty T regulatorowe, wolna encyklopedia
Central tolerance: what have we learned from mice?. „Semin Immunopathol". 30 (4), s. 399-409, grudzień 2008. DOI: 10.1007/ ... B7/CD28 in central tolerance: costimulation promotes maturation of regulatory T cell precursors and prevents their clonal ... Oral tolerance in the absence of naturally occurring Tregs. „J Clin Invest". 115 (7), s. 1923-1933, lipiec 2005. DOI: 10.1172/ ... Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single ...
In a process known as "Central Tolerance", T-cells are exposed to cortical epithelial cells that express a variety of different ... Xing Y, Hogquist KA (June 2012). "T-cell tolerance: central and peripheral". Cold Spring Harbor Perspectives in Biology. 4 (6 ... Tolerance to self-protein is crucial for overall wellbeing; when the body erroneously identifies self-proteins as "non-self", ...
Antigen transfer in the thymus
Two processes of central tolerance take place in thymic medulla, namely clonal deletion (recessive tolerance) and T Regulatory ... The most efficient subset in TRA presentation and both modes of central tolerance was found to be CD8α+ thymic-derived DCs ( ... Indispensability of DCs for the establishment of central tolerance was further verified by recent analysis, which revealed that ... Gallegos AM, Bevan MJ (October 2004). "Central tolerance to tissue-specific antigens mediated by direct and indirect antigen ...
Pelanda, Roberta; Torres, Raul M. (2012-04-01). "Central B-Cell Tolerance: Where Selection Begins". Cold Spring Harbor ... This negative selection process leads to a state of central tolerance, in which the mature B cells do not bind self antigens ...
Tolerogenic dendritic cell
Tolerogenic DCs are essential in maintenance of central and peripheral tolerance through induction of T cell clonal deletion, T ... Tol-DCs promotes central and peripheral tolerance. These tolerogenic properties are executed by deletion of T cells, induction ... Moreover, Ag-specific tolerance in humans can be induced in vivo via vaccination with Ag-pulsed ex vivo generated tolerogenic ... Therefore, CD83high IL-10DCs could be promising and great candidates for tolerance-inducing vaccination studies in vivo. In ...
In aging of the immune system is also a decrease in central tolerance and an increase in the number of autoreactive T cells. B ... APECED causes loss of central immune tolerance. Omenn syndrome manifests as GVHD (graft versus host disease)-like autoimmune ...
"Autonomous role of medullary thymic epithelial cells in central CD4(+) T cell tolerance". Nature Immunology. 11 (6): 512-9. doi ... Central memory T cells (TCM cells) express CD45RO, C-C chemokine receptor type 7 (CCR7), and L-selectin (CD62L). Central memory ... This process is an important component of central tolerance and serves to prevent the formation of self-reactive T cells that ... A T cell, or T lymphocyte, is a type of lymphocyte (a subtype of white blood cell) that plays a central role in cell-mediated ...
Metzger, T.C. (2011). "Control of Central and Peripheral Tolerance by Aire". Immunol Rev. 2011 May. 241 (1): 89-103. doi: ...
Hayreh, SS; Kolder, HE; Weingeist, TA (1980). "Central retinal artery occlusion and retinal tolerance time". Ophthalmology. 87 ... Hayreh, SS (1983). "Classification of central retinal vein occlusion". Ophthalmology. 90 (5): 458-74. doi:10.1016/s0161-6420(83 ... Neetens of the existence of the central artery of the optic nerve; Hayreh found instead that the artery did not exist. In 1961 ...
抗體 - 維基百科，自由的百科全書
Nemazee D. Receptor editing in lymphocyte development and central tolerance. Nat Rev Immunol. 2006, 6 (10): 728-740. PMID ...
Antibody - Simple English Wikipedia, the free encyclopedia
Nemazee D (2006). "Receptor editing in lymphocyte development and central tolerance". Nat Rev Immunol 6 (10): 728-40. doi: ...
Expresión en Corto International Film Festival
", "Identity" and "Liberty". In 2011 the festival's central theme will be "Tolerance". Film festivals in North and Central ...
Eagle Rock, Los Angeles
David Weberman (8 July 2016). Space and Pluralism: Can Contemporary Cities Be Places of Tolerance?. Central European University ...
Therefore, one of the most important roles of the thymus is the induction of central tolerance. ... The central nervous system also has lymphatic vessels, as discovered by the University of Virginia Researchers. The search for ... As a major lymphoid organ and a central player in the reticuloendothelial system, the spleen retains the ability to produce ... The primary or central lymphoid organs generate lymphocytes from immature progenitor cells. ...
... making it a type of negative selection or central tolerance. Central tolerance prevents B and T lymphocytes from reacting to ... Thus, the host develops a tolerance for this antigen, or a self tolerance. B and T lymphocytes are tested for their affinity ... It is one method of immune tolerance. Frank Macfarlane Burnet proposed autoreactive cells would be terminated before maturation ...
Thymic epithelial cell
Both cTEC and mTEC participate in imposing central and peripheral tolerance. cTECs play a key role in the positive selection ... Type 1 diabetes is a result of the absence of self-tolerance, which is characterized by a decreased expression of Insulin 1 and ... TECs, as a component of the thymus, play a key role in thymocyte development and self-tolerance, so their dysfunction causes ... Medulla is also important for implementation of self tolerance, which is mediated by CD4+CD25+Foxp3 nTreg cells. Foxp3 Treg ...
"Chilling tolerance of central European maize lines and their factorial crosses". Annals of Botany. 100 (6): 1315-1321. doi: ... Farooq, M., Aziz, T., Wahid, A., Lee, D. J., & Siddique, K. H. (2009). "Chilling tolerance in maize: agronomic and ... Another approach is to breed for increased chilling tolerance. This would make earlier sowing possible and elongate the ... which were more suitable to the colder climate in northern and central Europe than the varieties from South America. Rheintaler ...
Human chorionic gonadotropin
"Human Chorionic Gonadotropin as a Central Regulator of Pregnancy Immune Tolerance". The Journal of Immunology. 190 (6): 2650- ... These results suggest that hCG may be a link in the development of peritrophoblastic immune tolerance, and may facilitate the ...
Karen Koch (plant biologist)
2011-2014). Central focus is heat-tolerance of genes for kernel dry weight. UniformMu: A Transposon Resource for Mutagenesis in ... This sugar occupies a truly central position in vascular transport, carbon partitioning within the plant, and as a source of ...
T细胞 - 维基百科，自由的百科全书
Autonomous role of medullary thymic epithelial cells in central CD4(+) T cell tolerance. Nature Immunology. 2010-06, 11 (6): ... The role of peripheral T-cell deletion in transplantation tolerance. Philosophical Transactions of the Royal Society of London ...
Cortical thymic epithelial cells
... to eliminate T cells with self-reactive TCRs via processes of central tolerance e.g. negative selection and protect the body ... "Medullary Thymic Epithelial Stem Cells Maintain a Functional Thymus to Ensure Lifelong Central T Cell Tolerance". Immunity. 41 ... "Antigen presentation in the thymus for positive selection and central tolerance induction". Nature Reviews Immunology. 9 (12): ... "CCR7-Dependent Cortex-to-Medulla Migration of Positively Selected Thymocytes Is Essential for Establishing Central Tolerance". ...
Harald von Boehmer
Nature 351, 150 (1991). Central tolerance by deletion of immature T cells in TCR transgenic mice. Teho H. S., Kisielow, P., ... Kisielow, P., Blüthmann, H., Staerz, U. D., Steinmetz, M. and von Boehmer, H.: Tolerance in T cell receptor transgenic mice: ... Science 251, 1225 (1991). Peripheral tolerance by deletion of and reversible anergy in matureT cells. Borgulya, P., Kishi, H., ... Tolerance to histocompatibility determinants in tetraparental bone marrow chimeras. J. Exp. Med. 141, 322 (1975). Graft-versus- ...
The development of CentrAl. First International Conference on Damage Tolerance of Aircraft Structures. Delft, Netherlands. ... Its major advantages over conventional aluminum are: Better "damage tolerance" behavior, especially in impact and metal fatigue ... Central European Journal of Engineering. 2 (4): 603-611. Bibcode:2012CEJE....2..603M. doi:10.2478/s13531-012-0019-z. ISSN 1896- ... technology demonstrator that was partially made of FML and was based on the central fuselage of its ERJ-145 aircraft. Later, ...
December 2003). "An immunologically privileged retinal antigen elicits tolerance: major role for central selection mechanisms ...
Law of India
Manu's central philosophy was tolerance and pluralism, and was cited across Southeast Asia. Early in this period, which ... Laws passed by the Parliament of India and other pre-existing central laws on subjects classified as central subjects are ... namely the Central Board of Direct Taxes and Central Board of Excise and Customs with effect from 1 January 1964. This ... The Central Board of Direct Taxes (CBDT) is a part of the Department of Revenue in the Ministry of Finance, Government of India ...
Medullary thymic epithelial cells
mTECs possess the ability to deal with these autoreactive clones via mediation of the processes of central tolerance, namely ... "Macroautophagy substrates are loaded onto MHC class II of medullary thymic epithelial cells for central tolerance". The Journal ... "Autonomous role of medullary thymic epithelial cells in central CD4(+) T cell tolerance". Nature Immunology. 11 (6): 512-9. doi ... "Medullary thymic epithelial stem cells maintain a functional thymus to ensure lifelong central T cell tolerance". Immunity. 41 ...
Manu's central philosophy was tolerance and pluralism, and was cited across Southeast Asia. Early in this period, which finally ... and most of Central and South America. The primary contrast between the two systems is the role of written decisions and ...
inaction: Tolerance *Central. *Peripheral. *Clonal anergy. *Clonal deletion. *Tolerance in pregnancy. *Immunodeficiency ...
T细胞 - 维基百科，自由的百科全书
Autonomous role of medullary thymic epithelial cells in central CD4(+) T cell tolerance. Nature Immunology. 2010-06, 11 (6): ... The role of peripheral T-cell deletion in transplantation tolerance. Philosophical Transactions of the Royal Society of London ...
Type 2 diabetes
Impaired glucose tolerance. ≥ 7.8. ≥ 140. , 7.0. , 126. 42-46. 6.0-6.4 Diabetes mellitus. ≥ 11.1. ≥ 200. ≥ 7.0. ≥ 126. ≥ 48. ≥ ... and inappropriate regulation of metabolism by the central nervous system. However, not all people with insulin resistance ... In those with impaired glucose tolerance, diet and exercise either alone or in combination with metformin or acarbose may ... with a glucose tolerance test, two hours after the oral dose a plasma glucose ≥ 11.1 mmol/l (200 mg/dl) ...
In "central sensitization," nociceptive neurons in the dorsal horns of the spinal cord become sensitized by peripheral tissue ... drug sensitization or reverse tolerance - the escalating effect of a drug resulting from repeated administration at a given ... The changes of central sensitization occur after repeated trials to pain. Research from animals has consistently shown that ... tolerance - the diminishing effect of a drug resulting from repeated administration at a given dose ...
Level of measurement
Central tendency. The mode, i.e. the most common item, is allowed as the measure of central tendency for the nominal type ... Central tendency. The median, i.e. middle-ranked, item is allowed as the measure of central tendency; however, the mean (or ... Central tendency and statistical dispersion. The mode, median, and arithmetic mean are allowed to measure central ... Central tendency and statistical dispersion. The geometric mean and the harmonic mean are allowed to measure the central ...
... waltii collectively constituted a distinct clade of separate ancestry from the central clade in the genus Kluyveromyces. ... Due to the heat tolerance of K. marxianus, high heat fermentations are feasible, reducing the costs normally expended for ...
DuPen A, Shen D, Ersek M (September 2007). "Mechanisms of opioid-induced tolerance and hyperalgesia". Pain Manag Nurs. 8 (3): ... March 2004). "The cyclooxygenase isozyme inhibitors parecoxib and paracetamol reduce central hyperalgesia in humans". Pain. 108 ... December 2004). "Chronic oral Gabapentin reduces elements of central sensitization in human experimental Hyperalgesia". ... As it can be difficult to distinguish from tolerance, opioid-induced hyperalgesia is often compensated for by escalating the ...
Penn gained a reputation for benevolence and tolerance, but his efforts resulted in more effective colonization of the ... Killbuck, Ohio History Central. July 1, 2005. References. *Aberg, Alf. The People of New Sweden: Our Colony on the ...
Mann-Whitney U test
A measure of the central tendencies of the two groups (means or medians; since the Mann-Whitney U test is an ordinal test, ... we can also interpret the Mann-Whitney U test as assessing whether the Hodges-Lehmann estimate of the difference in central ...
His solution to anti-Semitism was a combination of a Jewish homeland, greater tolerance, and assimilation in other countries. ... Offers a systematic and analytic account of the central categories of Niebuhr's political theology and philosophy of history. ...
This means products can be more precision-engineered to for production to result in shorter lead times, tighter tolerances and ... effect on the central circulation or nervous system, diagnostic impact, or incorporation of a medicinal product. Certified ...
History and physical examination are central to the diagnostic workup in nephrology. The history typically includes the present ... replaces kidney function by inserting into the body a healthier kidney from an organ donor and inducing immunologic tolerance ...
In Central Italy, there are sauces such as tomato sauce, amatriciana, arrabbiata and the egg-based carbonara. Tomato sauces are ... C tolerance), must have undergone a heat treatment at least equivalent to pasteurisation, and must be sold within 5 days of the ... it was one of the first pasta factories of Central Europe. By 1867, Buitoni Company in Sansepolcro, Tuscany became an ... such as Central Argentina, and the eight southernmost Brazilian states (where macaroni are called macarrão, and more general ...
Withdrawal and tolerance. Withdrawal symptoms appear to be very rare with moclobemide compared to other antidepressants[ ... Coquoz D, Porchet HC, Dayer P (September 1993). "Central analgesic effects of desipramine, fluvoxamine, and moclobemide after ... Tolerance does not seem to occur; research has found that moclobemide retains its beneficial therapeutic properties in ... Moclobemide increases levels of extracellular monoamines and decreases levels of their metabolites in rat brains; tolerance to ...
... and develop tolerance and empathy. Group sessions that emphasize cooperation and cohesion can be effective in working with ... are central factors in Orff music therapy. The strong emphasis on social integration and the involvement of parents in the ... due to damage of the central nervous system), aphasia (defect in expression causing distorted speech), or language ...
Although learning in the Indigenous American communities is not always the central focus when participating in an activity, ... Communities that participate in observational learning promote tolerance and mutual understand of those coming from different ... It goes far beyond learning mundane tasks through rote imitation; it is central to children's gradual transformation into ...
Demographics of Brazil
Central-West. The Central-West region of Brazil was inhabited by diverse Indians when the Portuguese arrived in the early ... Immigrants found a strong social and cultural tolerance toward inter-racial marriage, including large numbers of Mulattoes ( ... During the 19th and 20th century, immigrants from the Netherlands populated the central and southern states of Brazil. ... Currently they number approximately 980,000, most of whom live in a compact settlement in south central Paraná ...
T細胞 - 維基百科，自由的百科全書
中樞性耐受（英語：Central tolerance）. *外周性耐受（英語：Peripheral tolerance） ...
Youth Climate Movement
These teams of volunteers organise themselves into different working groups and form the central organs of the movement, ...
顆粒白血球 - 維基百科，自由的百科全
中樞性耐受（英語：Central tolerance）. *外周性耐受（英語：Peripheral tolerance） ... Neutrophils, central cells in acute inflammation. Inflammation and Fever from Pathophysiology: Principles of Disease. Computing ...
The central government was responsible for funding the army, although Haugwitz instituted taxation of the nobility, who had ... Freedom of religion was granted only in the Declaration of Tolerance issued by Joseph immediately after Maria Theresa´s death.[ ... Roider, Karl A. (1972). "The Perils of Eighteenth-Century Peacemaking: Austria and the Treaty of Belgrade, 1739". Central ... never before had to pay taxes. Moreover, after Haugwitz was appointed the head of the new central administrative agency, ...
It is hollow in cross-section, with a relatively thin layer of flesh surrounding a central seed cavity filled with large, flat ... "Bitter melon (Momordica charantia) reduces adiposity, lowers serum insulin and normalizes glucose tolerance in rats fed a high ...
History of European Jews in the Middle Ages
Most fled to Poland, as it had a reputation for religious tolerance unparalleled during this era. This religious tolerance may ... By the 17th century a trickle back process began, with reverse migration back to central and western Europe, following pogroms ...
Menocal, María Rosa (2002). Ornament of the World: How Muslims, Jews and Christians Created a Culture of Tolerance in Medieval ... West Central Africa (Republic of the Congo, Democratic Republic of the Congo and Angola): 39.4% ... Afro-Spaniards are Spanish nationals of West/Central African ancestry. They today mainly come from Cameroon, Equatorial Guinea ... From the years 1500 to 1850, an estimated 3.5 million captives were forcibly shipped from West/Central Africa to Brazil. The ...
... the equivalence of purines or that of pyrimidines at twofold degenerate sites adds a further fault-tolerance.:531-532 ... Central dogma *DNA → RNA → Protein. *Special transfers *RNA→RNA. *RNA→DNA. *Protein→Protein ...
கிளையி உயிரணு - தமிழ் விக்கிப்பீடியா
Central tolerance) · புற பொறுதி (Peripheral tolerance) · படியாக்க வலுவிழப்பு (Clonal anergy) · படியாக்க நீக்கம் (Clonal ...
... has applications in statistical inference. For example, one might use it to fit an isotonic curve to the means of some set of experimental results when an increase in those means according to some particular ordering is expected. A benefit of isotonic regression is that it is not constrained by any functional form, such as the linearity imposed by linear regression, as long as the function is monotonic increasing. Another application is nonmetric multidimensional scaling, where a low-dimensional embedding for data points is sought such that order of distances between points in the embedding matches order of dissimilarity between points. Isotonic regression is used iteratively to fit ideal distances to preserve relative dissimilarity order. Software for computing isotone (monotonic) regression has been developed for the R statistical package , the Stata statistical package and the Python programming language . ...
W. Michael Blumenthal
In 1999, he received the Leo Baeck Medal for his humanitarian work promoting tolerance and social justice, as well as the Grand ... Director of Central Intelligence. *Stansfield M. Turner (1977-81). Advisor to the. President on National Security Affairs. * ...
Deadwood, South Dakota
In 1888, J.K.P. Miller and his associates founded a narrow-gauge railroad, the Deadwood Central Railroad, to serve their mining ... and a relatively high level of tolerance of different peoples existed in the frontier town. Wong Fee Lee arrived in Deadwood in ... K.P. Miller and his associates founded a narrow-gauge railroad, the Deadwood Central Railroad, in 1888, to serve their mining ...
T-cell tolerance: central and peripheral. - PubMed - NCBI
Citations may include links to full-text content from PubMed Central and publisher web sites. ... T-cell tolerance: central and peripheral.. Xing Y1, Hogquist KA.. Author information. 1. Center for Immunology, Department of ... Cell types in central tolerance. (Top) T cells are positively selected in the thymic cortex. Negative selection via clonal ... Recent advances in mechanistic studies of central and peripheral T-cell tolerance are promoting the development of therapeutic ...
... is the mechanism by which newly developing T cells and B cells are rendered non-reactive to ... tolerance. Immunity • Autoimmunity • Allergy • Tolerance (Central) • Immunodeficiency. Immunogenetics. Somatic hypermutation • ... Central tolerance is the mechanism by which newly developing T cells and B cells are rendered non-reactive to self. The ... Sprent J, Kishimoto H (2001). "The thymus and central tolerance". Philos Trans R Soc Lond B Biol Sci 356 (1409): 609-16. PMID ...
Modulation of Tumor Tolerance in Primary Central Nervous System Malignancies
... Theodore S. Johnson,1,2,3 David H. Munn,1,2,3 and ... the immune system by definition has never acquired central tolerance. Despite this, however, the immune system behaves as if it ... because they may be excluded from central tolerance by virtue of their cellular, anatomical, or developmental expression ... G. Kaur, S. J. Han, I. Yang, and C. Crane, "Microglia and central nervous system immunity," Neurosurgery Clinics of North ...
Receptor editing in lymphocyte development and central tolerance. - PubMed - NCBI
Generation of hematopoietic chimerism and induction of central tolerance - GREINER DALE L.
The invention relates to the methods for producing hematopoietic chimerism and central tolerance by peripheral tolerance ... "Central tolerance" is tolerance that is established in lymphocytes developing in central lymphoid organs; "peripheral tolerance ... The central tolerance produced by the methods described herein is durable, e.g., long-lasting, and leads to long term tolerance ... Finally, unlike methods that rely on peripheral tolerance, the new methods of inducing central tolerance described herein do ...
India a living example of religious tolerance: Dalai Lama | Central Tibetan Administration
... spirit of religious tolerance and for carrying different traditions together while addressing a press conference after a ... Indias religious tolerance a model for world, says His Holiness. *India illustrious example of religious harmony: Dalai Lama ... India is the best example of religious tolerance: Dalai Lama. *India is living example of religious harmony: His Holiness the ... "Religious tolerance is very important… although there are problems sometimes due to politicians who try to manipulate that," he ...
Central tolerance - Wikipedia
Central tolerance is not perfect, so peripheral tolerance exists as a secondary mechanism to ensure that T and B cells are not ... Peripheral tolerance is distinct from central tolerance in that it occurs once developing immune cells exit primary lymphoid ... Central tolerance is essential to proper immune cell functioning because it helps ensure that mature B cells and T cells do not ... Central tolerance, also known as negative selection, is the process of eliminating any developing T or B lymphocytes that are ...
Central Role of Gimap5 in Maintaining Peripheral Tolerance and T Cell Homeostasis in the Gut
... ,. Mediators of Inflammation,. vol ... Central Role of Gimap5 in Maintaining Peripheral Tolerance and T Cell Homeostasis in the Gut. ... Regardless, the detailed mechanistic insight into the loss of T cell survival and immunological tolerance in Gimap5sph/sph mice ... as well as Tr1 and Th3 cells . The effector pathways by which Tregs induce tolerance are multiple and include secretion of ...
Induction of Tolerance: Practice Essentials, Central (Intrathymic) Mechanisms of Tolerance, Peripheral (Nonthymic) Mechanisms...
Tolerance is generally accepted to be an active process and, in essence, a learning experience for T cells. ... Immunologic tolerance is a state of immune unresponsiveness specific to a particular antigen or set of antigens induced by ... Central (Intrathymic) Mechanisms of Tolerance. The chief mechanism of T-cell tolerance is the deletion of autoreactive T cells ... donor-specific tolerance has been termed prope tolerance  (from Latin prope "near") or minimal immunosuppression tolerance. ...
IJMS | Free Full-Text | A Central Role for Thiols in Plant Tolerance to Abiotic Stress
Here, we review the significance of protein and non-protein thiol compounds in relation to plant tolerance of abiotic stress. ... However, the molecular mechanisms of plant stress tolerance are not fully understood, and the data available is incomplete and ... which plays a central part in plant stress response and oxidative signalling and of glutathione-related enzymes, including ... concludes with a brief overview of and future perspectives for the involvement of plant thiols in abiotic stress tolerance. ...
Lactose Tolerance Came From Central Asia Approximately 4,000 Years Ago - Anthropology.net
This contradicts a long time understanding that the genetic mutation for lactose tolerance was… ... Lactose Tolerance Came From Central Asia Approximately 4,000 Years Ago. That recent study published in the journal Nature, that ... 3 thoughts on "Lactose Tolerance Came From Central Asia Approximately 4,000 Years Ago" ... The alleles earliest appearance in the dataset is in a central European Bell Beaker sample (individual I0112) dated to between ...
IJMS | Free Full-Text | Medullary Thymic Epithelial Cells and Central Tolerance in Autoimmune Hepatitis Development: Novel...
The approach involved liver-extrinsic genetic engineering that interfered with the induction of T-cell tolerance in the thymus ... In addition, approaches to mimic AIH-associated liver inflammation have instead led to liver tolerance, consistent with the ... central tolerance; peripheral tolerance; autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED); autoimmune ... central tolerance; peripheral tolerance; autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED); autoimmune ...
Induction of Central Tolerance - Muscular Dystrophy - Fitness VIP
Induction of Central Tolerance. Wed, 30 May 2012 , Muscular Dystrophy The induction of hematopoietic mixed chimerism, defined ... Induction of central tolerance by intrathymic injection of viral vectors has been tested in rodents, and offers alternatives to ... could be an approach to induce robust central tolerance. This strategy capitalizes on the use of nonmyeloablative hematopoietic ... antigen-specific tolerance (Ilan et al. 1996; Marodon et al. 2006). ...
JCI Insight - Combination central tolerance and peripheral checkpoint blockade unleashes antimelanoma immunity
Lymphocyte-driven regional immunopathology in pneumonitis caused by impaired central immune tolerance | Science Translational...
Lymphocyte-driven regional immunopathology in pneumonitis caused by impaired central immune tolerance ... Lymphocyte-driven regional immunopathology in pneumonitis caused by impaired central immune tolerance ... Lymphocyte-driven regional immunopathology in pneumonitis caused by impaired central immune tolerance ... Lymphocyte-driven regional immunopathology in pneumonitis caused by impaired central immune tolerance ...
Abstract 15421: Central Hemodynamic Response to Oral Glucose Loading Are Blunted in Patients with Impaired Glucose Tolerance or...
Abstract 15421: Central Hemodynamic Response to Oral Glucose Loading Are Blunted in Patients with Impaired Glucose Tolerance or ... Abstract 15421: Central Hemodynamic Response to Oral Glucose Loading Are Blunted in Patients with Impaired Glucose Tolerance or ... Abstract 15421: Central Hemodynamic Response to Oral Glucose Loading Are Blunted in Patients with Impaired Glucose Tolerance or ... Abstract 15421: Central Hemodynamic Response to Oral Glucose Loading Are Blunted in Patients with Impaired Glucose Tolerance or ...
Frontiers | Resting sympathetic baroreflex sensitivity in subjects with low and high tolerance to central hypovolemia induced...
2.2 ± 0.2 bursts•(100 beats)-1•mmHg-1, p=0.29). We conclude that tolerance to central hypovolemia is not related to either ... are attenuated in male and female subjects who have low tolerance (LT) to central hypovolemia induced by lower body negative ... are attenuated in male and female subjects who have low tolerance (LT) to central hypovolemia induced by lower body negative ... The ability to tolerate central hypovolemia is variable and physiological factors contributing to tolerance are emerging. We ...
BullyVille Central - Brains over Bullies™ • View topic - National no tolerance policy
B cell signalling in mechanisms of central and peripheral tolerance - Enlighten: Theses
Thalhamer, Theresa (2009) B cell signalling in mechanisms of central and peripheral tolerance. PhD thesis, University of ... Negative selection of self-reactive immature B cells constitutes a major mechanism of sustaining central tolerance. The WEHI- ... Tolerance against self is a necessary feature of the immune system to prevent autoimmunity. Hence during B cell development, a ... number of central and peripheral developmental checkpoints ensure the deletion of self-reactive B cells and selection of ...
The role of CCR4 and CCR7 in the establishment of central tolerance
The role of CCR4 and CCR7 in the establishment of central tolerance. ... To establish tolerance towards self-antigens, developing T cells in the thymus (thymocytes) undergo stringent selection ... In keeping with the importance of these two activities for the induction of self-tolerance, in the absence of CCR4, ... The cellular and molecular mechanisms governing thymocyte tolerance induction are incompletely understood. In this dissertation ...
Experimental occlusion of the central artery of the retina. IV: Retinal tolerance time to acute ischaemia. | British Journal of...
UBIRA ETheses - Investigating the role of accessory cells in the thymic microenvironment for central tolerance and thymus...
Cosway, Emilie Jade (2018). Investigating the role of accessory cells in the thymic microenvironment for central tolerance and ... Investigating the role of accessory cells in the thymic microenvironment for central tolerance and thymus regeneration ... Additionally, disruption of the medulla in Ltbr-/- mice was distinct from tolerance breakdown, which we instead found to ... Collectively these findings shed new light on accessory cells during key aspects of thymus tolerance and regeneration. ...
Specificity of Compensatory Reserve and Tissue Oxygenation as Early Predictors of Tolerance to Progressive Reductions in...
... of Compensatory Reserve and Tissue Oxygenation as Early Predictors of Tolerance to Progressive Reductions in Central Blood ... Consistent with our hypothesis, CRI detected central hypovolemia with significantly greater specificity than measures of tissue ... provided earlier indication of reduced central blood volume than standard vital signs (e.g., blood pressure, heart rate, ... we hypothesized that the CRI would provide greater sensitivity and specificity to detect progressive decrease in central ...
Central and Peripheral Autoantigen Presentation in Immune Tolerance - PubMed
These recent advances are bringing about a paradigm shift in our views about tolerance to self-molecules with tissue-restricted ... Recent studies in both humans and experimental rodent models provide new insight into key mechanisms regulating tolerance to ... Central and Peripheral Autoantigen Presentation in Immune Tolerance Alberto Pugliese. Immunology. Feb 2004 ... Thymic T-cell Tolerance of Neuroendocrine Functions: Physiology and Pathophysiology V Geenen et al. Cell Mol Biol (Noisy-le- ...
A SNP in intron 1 of TSHR controls its thymic expression and susceptibility to Graves' disease suggesting central tolerance...
These results constitute first evidence for the involvement of central tolerance in the loss of tolerance to TSHR in GD and ... A SNP in intron 1 of TSHR controls its thymic expression and susceptibility to Graves disease suggesting central tolerance ... del Pilar Armengol et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. ... and thereby induce central T cell tolerance. In order to understand the association between TSHR gene polymorphisms and GD we ...
PPT - Molecular mechanisms of immune tolerance Central tolerance induction in the B cell and T cell compartment Immune toleran...
Molecular mechanisms of immune tolerance Central tolerance induction in the B cell and T cell compartment Immune tolerance in ... Molecular mechanisms of immune tolerance Central tolerance induction in the B cell and T cell compartment Immune tolerance in ... Molecular mechanisms of immune tolerance Central tolerance induction in the B cell and T cell compartment Immune toleran ... Molecular mechanisms of immune tolerance Central tolerance induction in the B cell and T cell compartment Immune toleran - ...
Ex-vivo expanded DC induce donor-specific central and peripheral tolerance and prolong the acceptance of donor skin allografts
For central tolerance, injection of FLDCs induced antigen-specific clonal deletion of both CD8 and CD4 single-positive ... For central tolerance, injection of FLDCs induced antigen-specific clonal deletion of both CD8 and CD4 single-positive ... could induce allospecific central and peripheral tolerance after IV injection; B cells were used as a control. The results ... could induce allospecific central and peripheral tolerance after IV injection; B cells were used as a control. The results ...
Central tolerance requires a Bim | Arthritis Research & Therapy | Full Text
JCI Insight - Combination central tolerance and peripheral checkpoint blockade unleashes antimelanoma immunity
Combination central tolerance and peripheral checkpoint blockade unleashes antimelanoma immunity. Pearl Bakhru,1 Meng-Lei Zhu,1 ... Central T cell tolerance mechanisms protect against the development of autoimmunity, but also limit antitumor immunity (9-11). ... Enhancement of an anti-tumor immune response by transient blockade of central T cell tolerance. J Exp Med. 2014;211(5):761-768. ... Thus, a combination of central tolerance blockade and checkpoint inhibition may improve a therapeutic index, compared with ...
Control of central self-tolerance induction by autoreactive CD4+ thymocytes. - Immunology
AntigensAutoimmunityClonal deletionEpithelial cellsLymphocytesThymicPeripheryImmunologicImmunityAireImmunological toleranceThymocytesAbstractImmune systemBone marrowAnergyReceptorDeletionPathogenesisTolerogenicInduction of Central ToleranceNervous systemCellsPeripheral T-cell toleHypovolemiaRegulationOccursLoss of toleranceUnresponsivenessTregsRetinalRegulatory T ceAutoantigensMechanisms of immune toleranceResponsesDevelop toleranceRoleInhibitionReceptorsAntigen-presDrought-toleranceLymphoidMolecularBreakdown
- Thus, peripheral tolerance processes exist wherein self-reactive T cells become functionally unresponsive (anergy) or are deleted after encountering self-antigens outside of the thymus. (nih.gov)
- Central tolerance is essential to proper immune cell functioning because it helps ensure that mature B cells and T cells do not recognize self-antigens as foreign microbes. (wikipedia.org)
- 2] The end result of tolerance is a population of lymphocytes that are not reactive to self-antigens but may be able to recognize foreign, non-self antigens depending on the randomly arranged receptor. (wikipedia.org)
- Importantly, lymphocytes can only develop tolerance towards antigens that are present in the bone marrow (for B cells) and thymus (for T cells). (wikipedia.org)
- Immunologic tolerance is a state of immune unresponsiveness specific to a particular antigen or set of antigens induced by previous exposure to that antigen or set. (medscape.com)
- The approach involved liver-extrinsic genetic engineering that interfered with the induction of T-cell tolerance in the thymus, the very process thought to inhibit AIH induction by liver-specific expression of exogenous antigens. (mdpi.com)
- To establish tolerance towards self-antigens, developing T cells in the thymus (thymocytes) undergo stringent selection processes. (utexas.edu)
- TSHR belongs to the category of tissue-restricted antigens (TRAs), which are expressed by medullary thymic epithelial cells (mTECs) and thereby induce central T cell tolerance. (biomedcentral.com)
- Autoimmune predisposition in Down syndrome may result from a partial central tolerance failure due to insufficient intrathymic expression of AIRE and peripheral antigens. (bvsalud.org)
- Central tolerance i imposed largely within the interior, medullary region of the thymus, where thymocytes encounter a wide array of self-antigens expressed on stromal cells, namely dendritic cells and/or medullary thymic epithelial cells. (grantome.com)
- In a complementary set of traditional immunological approaches, murine models deficient for candidate GPCRs will be tested for overt autoimmunity, as well as for an inability to induce central tolerance to model medullary self- antigens. (grantome.com)
- Dendritic cells (DCs) play a significant role in establishing self -tolerance through their ability to present self-antigens to developing T cells in the thymus . (bvsalud.org)
- Medullary thymic epithelial cells (mTECs) serve an essential function in central tolerance by expressing peripheral-tissue antigens. (semanticscholar.org)
- Thymic B Cells Are Licensed to Present Self Antigens for Central T Cell Tolerance Induction. (semanticscholar.org)
- Self tolerance depends on mechanisms regulating T- and B-lymphocytes from the earliest stages when they first express self-reactive receptors in the thymus or bone marrow respectively and later when they encounter self antigens in the peripheral immune system or within the tissues themselves. (stembook.org)
- Aire is a transcriptional regulator that induces expression of tissue-restricted genes in the thymus, wherein central tolerance to many self-antigens is acquired. (hhs.gov)
- Aire ensures that tolerance to such antigens is established in developing T cells. (hhs.gov)
- Peripheral tolerance occurs at mature lymphocytes encounter self-antigens in peripheral tissues. (intechopen.com)
- Background Breakdown of humoral tolerance to RBC antigens may lead to autoimmune hemolytic anemia, a severe and sometimes fatal disease. (haematologica.org)
- The underlying mechanisms behind the breakdown of humoral tolerance to RBC antigens are poorly understood. (haematologica.org)
- Autoimmune hemolytic anemia (AIHA) consists of loss of tolerance to self-antigens on red blood cells (RBCs) in the humoral compartment. (haematologica.org)
- 8 , 9 Therefore, baseline humoral tolerance to RBC antigens appears to fail in up to 1-3/1,000 humans, indicating that tolerance mechanisms to RBC antigens are lost with considerable frequency. (haematologica.org)
- The relative inefficiency of humoral tolerance to RBC antigens can not be predicted, given the known characteristics of central B-cell tolerance. (haematologica.org)
- In the intestine, pAPCs including dendritic cells (DCs) and macrophages are strategically positioned to protect the gut while maintaining mucosal tolerance to food, self-antigens and microbiota. (nature.com)
- Tolerance against self is a necessary feature of the immune system to prevent autoimmunity. (gla.ac.uk)
- In keeping with the importance of these two activities for the induction of self-tolerance, in the absence of CCR4, autoreactive T cells are not efficiently eliminated and autoimmunity ensues. (utexas.edu)
- These results constitute first evidence for the involvement of central tolerance in the loss of tolerance to TSHR in GD and underscore the concept that variable expression levels of major target autoantigens in the thymus influence the predisposition to autoimmunity presumably by changing the threshold of tolerance. (biomedcentral.com)
- Autoimmunity results from a failure or breakdown of the mechanisms normally responsible for maintaining self-tolerance in B cells, T cells, or both. (slideserve.com)
- A causal link between autoimmune phenomena and skewed thymic development in these mice remains to be demonstrated, such that it is unclear if defects in peripheral tolerance contribute to autoimmunity. (biomedcentral.com)
- Our findings provide strong evidence for the fundamental role of AIRE and pGE, namely, central tolerance , in the predisposition to autoimmunity of DS individuals. (bvsalud.org)
- From studies of Autoimmune Polyglandular Syndrome-I patients along with mouse models of this disorder, we know that if central tolerance induction in the medulla is impaired, multi-organ autoimmunity ensues. (grantome.com)
- Autoimmunity occurs when self-reactive lymphocytes fail to succumb to normal tolerance mechanisms. (grantome.com)
- We identify potential associations between CNS autoimmunity susceptibility factors and thymic tolerance. (ox.ac.uk)
- The therapeutic manipulation of thymopoiesis has the potential to open up new treatment modalities, but a better understanding of thymic tolerance in CNS autoimmunity is required before this can be realised. (ox.ac.uk)
- Failure of Immunologic self-tolerance due to environmental and genetic factors may predipose the development of autoimmunity. (intechopen.com)
- While significant progress has been made in understanding the basic processes of both central and peripheral tolerance, the integration of these mechanisms in the context of the pathogenesis of autoimmunity is still in its infancy. (keystonesymposia.org)
- The thymus is essential for the prevention of autoimmunity through the induction of T cell tolerance and the generation of FoxP3 + regulatory T cells (Tregs). (jimmunol.org)
- An understanding of the pathways of immunologic tolerance and the mechanisms of its breakdown in autoimmunity are critical to developing future therapies for a variety of autoimmune disorders, such as diabetes and multiple sclerosis. (keystonesymposia.org)
- This Keystone meeting is centered at understanding tolerance and its breakdown and bridging the gap between basic, pre-clinical and clinical studies (the co-chairs have devoted their entire careers to understanding immune tolerance and autoimmunity, including novel therapies). (keystonesymposia.org)
- For central tolerance, injection of FLDCs induced antigen-specific clonal deletion of both CD8 and CD4 single-positive thymocytes. (garvan.org.au)
- However, these discoveries, and the host of allograft experiments and observations of twin chimerism they inspired, were seminal for the theories of immune tolerance formulated by Sir Frank McFarlane Burnet and Frank Fenner , who were the first to propose the deletion of self-reactive lymphocytes to establish tolerance, now termed clonal deletion . (wikipedia.org)
- Central tolerance prevents the maturation and egress of autoreactive immune cells, for example via clonal deletion of T cells in the thymus 1 . (stemcell.com)
- Multiple mechanisms of central tolerance take place in the thymus, where self-reactive T cells undergo clonal deletion or differentiation into regulatory T cells (Tregs) 1 . (stemcell.com)
- The expression of Aire in the thymus is critical for both central tolerance by clonal deletion, and for peripheral tolerance via the generation of Tregs 7 . (stemcell.com)
- The mechanisms by which B cells undergo tolerance, such as receptor editing, clonal deletion, and anergy, have been established in mice. (rupress.org)
- By following the fate of self-reactive human κ + B cells relative to nonautoreactive λ + cells, we show that tolerance of human B cells occurs at the first site of self-Ag encounter, the bone marrow, via a combination of receptor editing and clonal deletion. (rupress.org)
- Autonomous versus dendritic cell-dependent contributions of medullary thymic epithelial cells to central tolerance. (semanticscholar.org)
- Central nervous system tumors take advantage of the unique immunology of the CNS and develop exquisitely complex stromal networks that promote growth despite the presence of antigen-presenting cells and tumor-infiltrating lymphocytes. (hindawi.com)
- Central tolerance, also known as negative selection, is the process of eliminating any developing T or B lymphocytes that are reactive to self. (wikipedia.org)
- Through elimination of autoreactive lymphocytes, tolerance ensures that the immune system does not attack self peptides. (wikipedia.org)
- Suppressor lymphocytes mediate the tolerance by induction of a shift from a proinflammatory to an antiinflammatory immune response. (elsevier.com)
- For developing T lymphocytes, self-tolerance is induced in the central region of the thymus, the thymic medulla. (grantome.com)
- Wikipedia , PubMedHealth ) is an autoimmune disease wherein lymphocytes attack the central nervous system (CNS), including the brain and spinal cord, leading to relapsing, progressive loss of neurons. (blogspot.com)
- Central tolerance occurs at immature T and B lymphocytes in the thymus and bone marrow. (intechopen.com)
- Central to the development of type 1 diabetes are T lymphocytes with specific T-cell receptors that recognize islet molecules. (diabetesjournals.org)
- How thymic self-peptide expression patterns can dictate these mechanisms of tolerance had previously been unclear. (stemcell.com)
- This process of thymic self-tolerance induction is referred to as central tolerance. (grantome.com)
- CD4 T cell tolerance to nuclear proteins induced by medullary thymic epithelium. (semanticscholar.org)
- Even with defective thymic or peripheral tolerance, the development of CNS inflammation is rare. (ox.ac.uk)
- Specifically, the association between thymoma and paraneoplastic encephalitis and changes in T cell receptor excision circles in multiple sclerosis implicate thymic tolerance in these diseases. (ox.ac.uk)
- A loss of function at the AIRE locus is widely known to induce autoimmune activation against host tissues due to lack of central tolerance during thymic T cell development. (jyi.org)
- The deletion of autoreactive T cell clones through thymic-expressed TSAs is known as central tolerance. (jyi.org)
- Peripheral tolerance is distinct from central tolerance in that it occurs once developing immune cells exit primary lymphoid organs (the thymus and bone-marrow), prior to their export into the periphery. (wikipedia.org)
- In the periphery, DCs mediate peripheral tolerance by promoting regulatory T-cell development, induction of T-cell unresponsiveness, and deletion of activated T cells. (garvan.org.au)
- Any autoreactive cells that escape central tolerance and migrate to the periphery would then encounter mechanisms of peripheral tolerance, for example the induction of anergy or suppression by mechanisms of action of regulatory T cells 2 (Figure 1) . (stemcell.com)
- Hence, multiple mechanisms of peripheral tolerance, including the ones listed below, are in place to prevent these self-reactive cells from causing damage in the periphery. (stemcell.com)
- Moreover, the amount of available self-Ag and the genetics of the cord blood donor dictate the levels of central tolerance and autoreactive B cells in the periphery. (rupress.org)
- Induction of immunologic tolerance has been achieved and studied in numerous laboratory animal models, but it remains an elusive goal in clinical organ transplantation and in the management of autoimmune disease in humans. (medscape.com)
- Failure of immunologic tolerance may cause the development of autoimmune response and then autoimmune disease [ 4 , 5 ]. (intechopen.com)
- The maintenance of immune tolerance and gut homeostasis is achieved by an integrated regulation of innate and adaptive immunity but also involves the microbiome itself. (hindawi.com)
- Moreover, pharmacologic blockade of central T cell tolerance and peripheral checkpoint blockade in combination enhanced antimelanoma immunity in a synergistic manner. (jci.org)
- Together, these findings suggest that Aire-mediated central tolerance constrains the efficacy of peripheral checkpoint inhibition and point to simultaneous blockade of Aire and checkpoint inhibitors as a novel strategy to enhance antimelanoma immunity. (jci.org)
- The fate of these cells is dictated by a series of checkpoints that regulate the quality and magnitude of T cell-mediated immunity, known as tolerance checkpoints. (nature.com)
- The intestinal immunity and tolerance are orchestrated by both the innate and the adaptive immune system. (nature.com)
- However, the role of gp96 in regulating CD11c + APCs in the gut immunity and tolerance is unknown. (nature.com)
- In the case of T cell central tolerance, additional sources of antigen are made available in the thymus by the action of the transcription factor AIRE . (bionity.com)
- The thymuses of these DS individuals contained significantly lower levels of AIRE and thyroglobulin , to which tolerance is typically lost in autoimmune thyroiditis leading to hypothyroidism . (bvsalud.org)
- Distinct contributions of Aire and antigen-presenting-cell subsets to the generation of self-tolerance in the thymus. (semanticscholar.org)
- In this project, we aim to define the role of Aire in immune tolerance to the fetus, elucidate its regulation by sex hormones, and clarify its immune- independent role in reproduction. (hhs.gov)
- We will test the overall hypothesis that Aire is required for central immune tolerance the fetus, and that it functions in parallel within the uterus and ovary to support fertility. (hhs.gov)
- Determine the impact of Aire deficiency on maternal immune tolerance to the fetus. (hhs.gov)
- Ascertain the functional connection between sex hormones and Aire in maternal central tolerance to the fetus. (hhs.gov)
- Although little is known about the precise mechanisms that control TSA expression in TECs, the transcription factor autoimmune regulator (Aire) is central to TSA expression ( 5 ). (jimmunol.org)
- AIRE expands: new roles in immune tolerance and beyond. (medlineplus.gov)
- Therefore, even APECED patients with similar mutations at the AIRE locus may have dissimilar symptoms due to variation in specific self-antigen tolerance (De Martino et al. (jyi.org)
- Here, we discuss how defects in Gimap5 function impair immunological tolerance and lymphocyte survival and ultimately drive the development of CD4 + T cell-mediated early-onset colitis. (hindawi.com)
- Immune tolerance , or immunological tolerance , or immunotolerance , is a state of unresponsiveness of the immune system to substances or tissue that have the capacity to elicit an immune response in given organism. (wikipedia.org)
- Control of central self-tolerance induction by autoreactive CD4+ thymocytes. (ox.ac.uk)
- abstract = "Understanding factors that promote pulmonary tolerance to long-term oxidant injury is essential to evaluating health risks in humans. (elsevier.com)
- This is problematic since these B and T cells would, if activated, mount an immune system attack against self if not killed or inactivated by central tolerance mechanisms. (wikipedia.org)
- 2] Therefore, without central tolerance, the immune system could attack self, which is not sustainable and could result in an autoimmune disorder. (wikipedia.org)
- The fact that APCs expressing insulin have been demonstrated in both thymus and peripheral lymphoid tissues suggests that they may play a role in insulin presentation in both the central and peripheral immune system. (nih.gov)
- Central tolerance is the main way the immune system learns to discriminate self from non-self. (wikipedia.org)
- Peripheral tolerance is key to preventing over-reactivity of the immune system to various environmental entities ( allergens , gut microbes , etc. (wikipedia.org)
-  In addition, inducing peripheral tolerance in the local microenvironment is a common survival strategy for a number of tumors that prevents their elimination by the host immune system. (wikipedia.org)
- Lymphocyte maturation (and central tolerance) occurs in primary lymphoid organs such as the bone marrow and the thymus. (wikipedia.org)
- Tolerance is classified into central tolerance or peripheral tolerance depending on where the state is originally induced-in the thymus and bone marrow (central) or in other tissues and lymph nodes (peripheral). (wikipedia.org)
- Moreover, depending on the location of the self-Ag, tolerance is defined as central (i.e., in the bone marrow) or peripheral (i.e., in other tissues). (rupress.org)
- Induction of anergy (a state of non-reactivity) T cell central tolerance occurs in the thymus. (wikipedia.org)
- Negative selection, regulatory T cells, anergy, activation-induced cell death, immune suppression, receptor editing are examples of important steps of immune tolerance. (intechopen.com)
- 10 Establishment of tolerance can lead to deletion, anergy, or receptor editing such that the immunoglobulin is no longer autoreactive. (haematologica.org)
- In this Perspective, we discuss the mediators and networks that control the six main peripheral tolerance checkpoints throughout the life of a T cell: quiescence, ignorance, anergy, exhaustion, senescence and death. (nature.com)
- Mechanisms of central and peripheral tolerance (anergy, deletion and suppression). (unibo.it)
- Receptor editing in lymphocyte development and central tolerance. (nih.gov)
- We generated T cell receptor transgenic models of these CDS+ T cells and found that an unusual form of tolerance allows CDS+ T cells expressing a high affinity T cell receptor for MBP to escape tolerance and populate the peripheral repertoire. (grantome.com)
- This might explain why ES cell-derived tissues are so amenable to tolerance induction protocols, such as co-receptor blockade with monoclonal antibodies, when compared to skin grafts. (stembook.org)
- To assess the sensitivity of B cell tolerance with respect to receptor/autoantigen affinity, we identified low affinity ligands to the 3-83 (anti-major histocompatibility complex class I) antibody and tested the ability of these ligands to induce central and peripheral tolerance in 3-83 transgenic mice. (scripps.edu)
- The influence of CeA administration of GABA B receptor agonist and antagonist on the expression and acquisition of morphine-induced incentive tolerance using conditioned place preference (CPP) paradigm was investigated in the present study. (ac.ir)
- GABA B receptor agonist, baclofen (1.5, 6 and 12 µg/rat) or GABA B receptor antagonist, CGP35348 (1.5, 6 and 12 µg/rat) were injected into the CeA 5 min before the experiments in the test day (expression of tolerance) or 5 min before each injection of morphine (12.5 mg/kg) (acquisition of tolerance). (ac.ir)
- 7. Trujillo KA, Akil H. Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801. (ac.ir)
- Hence during B cell development, a number of central and peripheral developmental checkpoints ensure the deletion of self-reactive B cells and selection of tolerant B cells. (gla.ac.uk)
- Central tolerance involves the deletion of self-reactive T cells in the thymus. (infobarrel.com)
- Peripheral tolerance uses mechanisms of INDIFFERENCE, DELETION AND REGULATORY T CELLS to control this problem. (infobarrel.com)
- As the autoreactive T cells are present but non-responsive, these data indicate that factors that reverse T-cell non-responsiveness may be central to the pathogenesis of autoimmune hemolytic anemia. (haematologica.org)
- 7 The basic pathogenesis of primary AIHA is poorly understood, but clearly results from a failure of tolerance mechanisms. (haematologica.org)
- In addition, approaches to mimic AIH-associated liver inflammation have instead led to liver tolerance, consistent with the high tolerogenic capacity of the liver. (mdpi.com)
Induction of Central Tolerance1
- Induction of central tolerance by intrathymic injection of viral vectors has been tested in rodents, and offers alternatives to antigen-specific tolerance (Ilan et al. (fitness-vip.com)
- Central nervous system (CNS) tumors account for high rates of morbidity and mortality [ 1 ]. (hindawi.com)
- Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS) that is believed to have an autoimmune etiology. (grantome.com)
- Autoimmune diseases of the central nervous system (CNS) are associated with high levels of morbidity and economic cost. (ox.ac.uk)
- Central tolerance is the mechanism by which newly developing T cells and B cells are rendered non-reactive to self. (bionity.com)
- In this paper, we place an emphasis on the role of tumor-infiltrating myeloid cells in maintaining stromal and vascular quiescence, and we underscore the importance of indoleamine 2,3-dioxygenase activity as a myeloid-driven tumor tolerance mechanism. (hindawi.com)
- Central tolerance is not perfect, so peripheral tolerance exists as a secondary mechanism to ensure that T and B cells are not self-reactive once they leave primary lymphoid organs. (wikipedia.org)
- More specifically, central tolerance is necessary because T cell receptors (TCRs) and B cell receptors (BCRs) are made by cells through random somatic rearrangement. (wikipedia.org)
- Steps of T cell tolerance During positive selection, T cells are checked for their ability to bind peptide-MHC complexes with affinity. (wikipedia.org)
- Tolerance is generally accepted to be an active process and, in essence, a learning experience for T cells. (medscape.com)
- The induction of hematopoietic mixed chimerism, defined as the coexistence of donor and recipient hematopoietic cells, could be an approach to induce robust central tolerance. (fitness-vip.com)
- Negative selection of self-reactive immature B cells constitutes a major mechanism of sustaining central tolerance. (gla.ac.uk)
- Regulatory T cells suppress immune responses initiated by auto-reactive T cells that escaped from thymus, and are therefore essential for maintaining self-tolerance. (utexas.edu)
- Collectively these findings shed new light on accessory cells during key aspects of thymus tolerance and regeneration. (bham.ac.uk)
- There is, indeed, mounting evidence that selected antigen-presenting cells (APCs) have the ability to synthesize and express self-molecules, and that such expression is critical for self-tolerance. (nih.gov)
- Dendritic cells (DCs) are known to regulate immune responses by inducing both central and peripheral tolerance. (garvan.org.au)
- The results showed that only FLDCs reached the thymus after injection and that these cells induced both central and peripheral tolerance to donor major histocompatibility complexes. (garvan.org.au)
- The phenomenon of immune tolerance was first described by Ray D. Owens in 1945, who noted that dizygotic twin cattle sharing a common placenta also shared a stable mixture of each other's red blood cells (though not necessarily 50/50), and retained that mixture throughout life. (wikipedia.org)
- The aim of this study was to test whether induction of oral tolerance to proteins extracted from inflammatory colon alleviates experimental colitis, and whether oral tolerization mediated by suppressor cells can induce immune tolerance. (elsevier.com)
- The over-arching hypothesis guiding these studies is that myelin-specific CDS+ T cells differ from CD4+ T cells in the mechanisms used to escape tolerance, in their recognition of targets cells in the CNS and in the pathologic consequences of antigen recognition in the CNS. (grantome.com)
- Although most autoreactive T cells are deleted or converted into Tregs during their development in the thymus, some self-reactive cells will escape these mechanisms of central tolerance. (stemcell.com)
- however, in the presence of inflammation, tolerance-prone RTEs retain the ability to convert into fully competent effector T cells. (stemcell.com)
- These studies will illuminate molecular mechanisms that promote thymocyte migration into the medulla and interactions with medullary stromal cells to promote central tolerance, thus broadening our understanding of the etiology of autoimmune diseases. (grantome.com)
- 2010 ). Corbascio and colleagues have also shown that a cocktail of costimulation blocking reagents, including anti- CD40L , anti- LFA-1 , and CTLA4 -Ig, is sufficient to induce tolerance to human ES cells transplanted to an immunologically privileged site such as the testis of C57BL/6 mice (Grinnemo et al. (stembook.org)
- To study how autoreactive human B cells undergo tolerance, we developed a novel humanized mouse model. (rupress.org)
- Sprent, J. Central tolerance of T cells. (springer.com)
- Dysfunction of central tolerance in the thymus, or in peripheral tolerance, such as regulatory T cells, could allow development of GD. (frontiersin.org)
- However, whether this failure is central versus peripheral and at the level of T and/or B cells remains unresolved. (haematologica.org)
- Elegant studies of central T and B cell tolerance have been performed, leading to the identification of multiple mechanisms that remove or silence autoreactive cells during their maturation, but also reminding us that some autoreactive cells do mature to immunocompetence in all individuals. (keystonesymposia.org)
- Low avidity recognition of self-antigen by T cells permits escape from central tolerance. (nature.com)
- Hasegawa, H. & Matsumoto, T. Mechanisms of tolerance induction by dendritic cells in vivo. (nature.com)
- Tolerance is induced as the T cells are being made. (infobarrel.com)
- In "central tolerance," newly minted T-cells and B-cells are exposed to self tissues and all the potentially antigenic molecules they could eventually see. (scienceblogs.com)
- many weakly self-reactive T-cells and B-cells manage to escape central tolerance. (scienceblogs.com)
- In other words, boys have 10-13 years to develop potentially ball-busting immune cells before the constituent parts are available to clear by central tolerance. (scienceblogs.com)
Peripheral T-cell tole1
- Recent advances in mechanistic studies of central and peripheral T-cell tolerance are promoting the development of therapeutic strategies to treat autoimmune disease and cancer and improve transplantation outcome. (nih.gov)
- The ability to tolerate central hypovolemia is variable and physiological factors contributing to tolerance are emerging. (frontiersin.org)
- We tested the hypothesis that resting muscle sympathetic nerve activity (MSNA) and sympathetic baroreflex sensitivity (BRS) are attenuated in male and female subjects who have low tolerance (LT) to central hypovolemia induced by lower body negative pressure (LBNP). (frontiersin.org)
- We conclude that tolerance to central hypovolemia is not related to either resting MSNA or sympathetic BRS. (frontiersin.org)
- Central hypovolemia occurs during orthostasis (upright posture) as blood pools in the legs due to gravity, and also during hemorrhage as blood volume decreases. (frontiersin.org)
- Low tolerance to central hypovolemia has critical implications during both circumstances. (frontiersin.org)
- Trauma patients with low tolerance to hypovolemia will reach the point of cardiovascular collapse (hemodynamic instability resulting from the inability of cardiovascular mechanisms to compensate for blood loss) in a shorter amount of time for similar blood loss, and thus may require life-saving interventions sooner than patients with high tolerance. (frontiersin.org)
- Identifying physiological and/or physical factors which influence tolerance may help elucidate the mechanism, and lead to potential identification of individuals with low tolerance to central hypovolemia prior to the onset of symptoms. (frontiersin.org)
- Tolerance to central hypovolemia is associated with maintenance of adequate perfusion pressure (i.e., arterial blood pressure) to vital organs. (frontiersin.org)
- Therefore, we hypothesize that the baseline sensitivity of the autonomic baroreflex responsible for the control of cardiac output and peripheral vascular resistance would be less sensitive in individuals who display low tolerance to central hypovolemia. (frontiersin.org)
- Consistent with our hypothesis, CRI detected central hypovolemia with significantly greater specificity than measures of tissue metabolism. (ovid.com)
- The current study investigates the novel role of central α-klotho in the regulation of NPY/AgRP neurons and whole-body metabolism via an FGFR/PI3K mechanism. (diabetesjournals.org)
- The results of these experiments are expected to provide highly novel insight into as-yet unexplored mechanisms of maternal tolerance to the fetal-placental unit, female fertility, and the regulation thereof by sex hormones, greatly advancing our understanding of maternal tolerance to the fetal allograft. (hhs.gov)
- Identification of the Arabidopsis dry2/sqe1-5 mutant reveals a central role for sterols in drought tolerance and regulation of reactive oxygen species. (ox.ac.uk)
- As RHD2 NADPH oxidase is de-localized in dry2/sqe1-5 root hairs, we propose that sterols play an essential role in the localization of NADPH oxidases required for regulation of reactive oxygen species, stomatal responses and drought tolerance. (ox.ac.uk)
- Here, we compare and contrast the T cell tolerance checkpoints and discuss their specific roles, with the aim of providing an integrated view of T cell peripheral tolerance and fate regulation. (nature.com)
- Central tolerance in the Bcell compartment occurs as a result of exposure to autoantigens at several checkpoints during B-cell development. (haematologica.org)
- For this reason self reactivity never occurs in the innate immune response and so it has no need to maintain self tolerance. (infobarrel.com)
Loss of tolerance1
- In this application, we will investigate the molecular mechanisms underlying both the CDS+ T cell tolerance and the loss of tolerance due to infection in this model. (grantome.com)
- Transplant tolerance is defined as a state of donor-specific unresponsiveness without a need for ongoing pharmacologic immunosuppression. (medscape.com)
- For peripheral tolerance, injection of FLDCs induced donor-specific T-cell unresponsiveness and prolonged survival of donor-derived skin grafts. (garvan.org.au)
- FOXP3 remains the most reliable marker of Tregs to date, and the importance of Tregs in maintaining immune tolerance continues to be highlighted. (stemcell.com)
- IV: Retinal tolerance time to acute ischaemia. (bmj.com)
- How is hyperbaric oxygen therapy used to treat central retinal artery occlusion (CRAO)? (medscape.com)
- Treatment options for central retinal artery occlusion. (medscape.com)
- Central retinal artery occlusion and retinal tolerance time. (medscape.com)
- Optic disk and retinal nerve fiber layer damage after transient central retinal artery occlusion: an experimental study in rhesus monkeys. (medscape.com)
- Tobalem S, Schutz JS, Chronopoulos A. Central retinal artery occlusion - rethinking retinal survival time. (medscape.com)
- The incidence of central retinal artery occlusion in Olmsted County, Minnesota. (medscape.com)
- Diagnosis and Management of Central Retinal Artery Occlusion. (medscape.com)
- Clinical characteristics and outcome of current standard management of central retinal artery occlusion. (medscape.com)
- Cardiovascular Risk Factors in Central Retinal Artery Occlusion: Results of a Prospective and Standardized Medical Examination. (medscape.com)
- Central Retinal Artery Occlusion and Cerebral Infarction Following Stem Cell Injection for Baldness. (medscape.com)
- Risk and Risk Periods for Stroke and Acute Myocardial Infarction in Patients with Central Retinal Artery Occlusion. (medscape.com)
- Ocular neovascularization in eyes with a central retinal artery occlusion or a branch retinal artery occlusion. (medscape.com)
- The central retinal artery, a branch of the ophthalmic artery, enters the eye through the optic disc and divides into multiple branches to perfuse the inner layers of the retina. (medscape.com)
Regulatory T ce1
- As a result, regulatory T cell generation is increased in CCR7-deficient mice, especially at the early neonatal stage, when regulatory T cell induction is particularly critical for the establishment of self-tolerance. (utexas.edu)
- When individuals having susceptible genetic background are exposed to environmental factors (e.g., iodine, smoking, infections, and stress, and others so far undisclosed), thyroid autoantigens break "self-tolerance" and AITDs develop ( 2 ). (frontiersin.org)
- This process generates central tolerance to autoantigens. (news-medical.net)
Mechanisms of immune tolerance1
- Although the concept of central and peripheral tolerance has long been established, researchers continue to uncover previously unknown mechanisms of immune tolerance. (stemcell.com)
- We tested the hypothesis that central hemodynamic responses to oral glucose loading were different according to the status of glucose tolerance. (ahajournals.org)
- Our data suggested that central hemodynamic responses to oral glucose loading were blunted in patients with impaired glucose tolerance or diabetes. (ahajournals.org)
- Pleiotropic Cyclophilin PpiB Controls Cysteine-Tolerance, Toxin Production, the Central Metabolism and Multiple Stress Responses. (helmholtz-hzi.de)
- A strategy to develop tolerance would also be of value in autoimmune diseases, such as juvenile-onset diabetes mellitus , rheumatoid arthritis , and multiple sclerosis . (medscape.com)
- Administration of one daily dose of morphine (12.5 mg/kg) for 3 days in order to develop tolerance to the drug reduced the conditioning induced by morphine (7.5 mg/kg, SC). (ac.ir)
- In this proposal, the role of candidate GPCRs in promoting medullary entry and self-tolerance will be evaluated. (grantome.com)
- However, the central role of α-klotho in metabolism remains largely unexplored. (diabetesjournals.org)
- The current study investigated the potential role of central α-klotho to modulate neuropeptide Y/agouti-related peptide (NPY/AgRP)-expressing neurons, energy balance, and glucose homeostasis. (diabetesjournals.org)
- Thus, uveitis-susceptible individuals display a detectable and functionally significant tolerance to their target antigen, in which central mechanisms play a prominent role. (elsevier.com)
- Central nucleus of amygdala (CeA) is the most important region for morphine-induced reward, and GABAergic system plays an important role on morphine reinforcement. (ac.ir)
- Our purpose was to evaluate the role of CeA GABA B receptors in morphine tolerance. (ac.ir)
- 2. Parvardeh S, Moghimi M, Eslami P, Masoudi A. α-Terpineol attenuates morphine-induced physical dependence and tolerance in mice: role of nitric oxide. (ac.ir)
- 2013, Graduate Research, Investigating the Role of HMX1 in ROS Tolerance During Mitosis and Meiosis in Saccharomyces Cerevisiae. (cmich.edu)
- Investigating the Role of HMX1 in ROS Tolerance Du. (cmich.edu)
- Lymphokines and the immune response: the central role of interleukin-2. (springer.com)
- Furthermore, central α-klotho inhibition via an anti-α-klotho antibody impaired glucose tolerance. (diabetesjournals.org)
- Does T-cell tolerance require a dedicated antigen-presenting cell? (springer.com)
- Here we evaluated how phyB modulates this drought-tolerance response by comparing wild-type Arabidopsis thaliana adult plants to the null phyB in response to water shortage. (uba.ar)
- This review addresses recent literature and emerging concepts about the expression of self-molecules in the thymus and peripheral lymphoid tissues and its relation to self-tolerance. (nih.gov)
- However, the molecular mechanisms of plant stress tolerance are not fully understood, and the data available is incomplete and sometimes contradictory. (mdpi.com)
- First, the roles of the amino acids cysteine and methionine, are discussed, followed by an extensive discussion of the low-molecular-weight tripeptide, thiol glutathione, which plays a central part in plant stress response and oxidative signalling and of glutathione-related enzymes, including those involved in the biosynthesis of non-protein thiol compounds. (mdpi.com)
- The cellular and molecular mechanisms governing thymocyte tolerance induction are incompletely understood. (utexas.edu)
- The novel functions of CCR4 and CCR7 discovered by our studies provide new insights into the cellular and molecular mechanisms that govern T cell tolerance induction and will provide rationale for development of new therapies for autoimmune disorders. (utexas.edu)
- Finally, unbiased gain-of-function screens will identify additional molecular candidates that promote thymocyte medullary entry and self-tolerance. (grantome.com)
- Additionally, disruption of the medulla in Ltbr-/- mice was distinct from tolerance breakdown, which we instead found to correlate to reduced DC and impaired negative selection. (bham.ac.uk)