Self Tolerance: The normal lack of the ability to produce an immunological response to autologous (self) antigens. A breakdown of self tolerance leads to autoimmune diseases. The ability to recognize the difference between self and non-self is the prime function of the immune system.Central Tolerance: The mechanism, in central lymphoid organs (THYMUS; BONE MARROW), that prevents immature lymphocytes from reacting to SELF-ANTIGENS. This is accomplished by CLONAL ANERGY and CLONAL DELETION.Immune Tolerance: 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.Peripheral Tolerance: The mechanism, in peripheral lymphoid organs (LYMPH NODES; SPLEEN; TONSILS; and mucosal-associated lymphoid tissue), that prevents mature lymphocytes from reacting to SELF-ANTIGENS. This is accomplished through a variety of means including CLONAL ANERGY and CLONAL DELETION.Autoantigens: Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.Drug Tolerance: 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.Thymus Gland: 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.Clonal Deletion: Removal, via CELL DEATH, of immature lymphocytes that interact with antigens during maturation. For T-lymphocytes this occurs in the thymus and ensures that mature T-lymphocytes are self tolerant. B-lymphocytes may also undergo clonal deletion.T-Lymphocytes, Regulatory: CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Mice, Inbred C57BLAutoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.T-Lymphocytes: 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.Lymphocyte Activation: 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.Glucose Tolerance Test: A test to determine the ability of an individual to maintain HOMEOSTASIS of BLOOD GLUCOSE. It includes measuring blood glucose levels in a fasting state, and at prescribed intervals before and after oral glucose intake (75 or 100 g) or intravenous infusion (0.5 g/kg).Autoimmune Diseases: Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.Transplantation Tolerance: An induced state of non-reactivity to grafted tissue from a donor organism that would ordinarily trigger a cell-mediated or humoral immune response.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.Mice, Knockout: 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.Dendritic Cells: 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).Polyendocrinopathies, Autoimmune: 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.CD4-Positive T-Lymphocytes: 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.Mice, Inbred BALB CClonal Anergy: Functional inactivation of T- or B-lymphocytes rendering them incapable of eliciting an immune response to antigen. This occurs through different mechanisms in the two kinds of lymphocytes and can contribute to SELF TOLERANCE.Mice, Inbred NOD: A strain of non-obese diabetic mice developed in Japan that has been widely studied as a model for T-cell-dependent autoimmune insulin-dependent diabetes mellitus in which insulitis is a major histopathologic feature, and in which genetic susceptibility is strongly MHC-linked.T-Lymphocyte Subsets: A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.Antigen-Presenting Cells: 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.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.B-Lymphocytes: Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.Skin Transplantation: The grafting of skin in humans or animals from one site to another to replace a lost portion of the body surface skin.Autoantibodies: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (IMMUNOTHERAPY, ADOPTIVE).Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily.CD8-Positive T-Lymphocytes: A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.Epithelial Cells: 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.Signal Transduction: 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.Forkhead Transcription Factors: A subclass of winged helix DNA-binding proteins that share homology with their founding member fork head protein, Drosophila.Programmed Cell Death 1 Ligand 2 Protein: A costimulatory B7 antigen that has specificity for the T-CELL receptor PROGRAMMED CELL DEATH 1 RECEPTOR. It is closely-related to CD274 antigen; however, its expression is restricted to DENDRITIC CELLS and activated MACROPHAGES.Glucose Intolerance: 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.Spleen: An encapsulated lymphatic organ through which venous blood filters.Antigens, CD274: An inhibitory B7 antigen that has specificity for the T-CELL receptor PROGRAMMED CELL DEATH 1 PROTEIN. CD274 antigen provides negative signals that control and inhibit T-cell responses and is found at higher than normal levels on tumor cells, suggesting its potential role in TUMOR IMMUNE EVASION.Antigens: Substances that are recognized by the immune system and induce an immune reaction.CTLA-4 Antigen: An inhibitory T CELL receptor that is closely related to CD28 ANTIGEN. It has specificity for CD80 ANTIGEN and CD86 ANTIGEN and acts as a negative regulator of peripheral T cell function. CTLA-4 antigen is believed to play role in inducing PERIPHERAL TOLERANCE.Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium.Salt-Tolerance: The ability of organisms to sense and adapt to high concentrations of salt in their growth environment.Antigens, CD: Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.Interleukin-2 Receptor alpha Subunit: A low affinity interleukin-2 receptor subunit that combines with the INTERLEUKIN-2 RECEPTOR BETA SUBUNIT and the INTERLEUKIN RECEPTOR COMMON GAMMA-CHAIN to form a high affinity receptor for INTERLEUKIN-2.Programmed Cell Death 1 Receptor: An inhibitory T-lymphocyte receptor that has specificity for CD274 ANTIGEN and PROGRAMMED CELL DEATH 1 LIGAND 2 PROTEIN. Signaling by the receptor limits T cell proliferation and INTERFERON GAMMA synthesis. The receptor also may play an essential role in the regulatory pathway that induces PERIPHERAL TOLERANCE.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Antigen Presentation: The process by which antigen is presented to lymphocytes in a form they can recognize. This is performed by antigen presenting cells (APCs). Some antigens require processing before they can be recognized. Antigen processing consists of ingestion and partial digestion of the antigen by the APC, followed by presentation of fragments on the cell surface. (From Rosen et al., Dictionary of Immunology, 1989)Blood Glucose: Glucose in blood.Adaptation, Physiological: The non-genetic biological changes of an organism in response to challenges in its ENVIRONMENT.Flow Cytometry: 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.Exercise Tolerance: The exercise capacity of an individual as measured by endurance (maximal exercise duration and/or maximal attained work load) during an EXERCISE TEST.Antigens, Differentiation: Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation.Interleukin-10: A cytokine produced by a variety of cell types, including T-LYMPHOCYTES; MONOCYTES; DENDRITIC CELLS; and EPITHELIAL CELLS that exerts a variety of effects on immunoregulation and INFLAMMATION. Interleukin-10 combines with itself to form a homodimeric molecule that is the biologically active form of the protein.Antigens, CD80: A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CTLA-4 ANTIGEN with high specificity and to CD28 ANTIGEN with low specificity. The interaction of CD80 with CD28 ANTIGEN provides a costimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.Droughts: Prolonged dry periods in natural climate cycle. They are slow-onset phenomena caused by rainfall deficit combined with other predisposing factors.Transplantation, Homologous: Transplantation between individuals of the same species. Usually refers to genetically disparate individuals in contradistinction to isogeneic transplantation for genetically identical individuals.Thymectomy: Surgical removal of the thymus gland. (Dorland, 28th ed)Interleukin-2: A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.Diabetes Mellitus, Type 1: A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence.Receptors, Interleukin-2: Receptors present on activated T-LYMPHOCYTES and B-LYMPHOCYTES that are specific for INTERLEUKIN-2 and play an important role in LYMPHOCYTE ACTIVATION. They are heterotrimeric proteins consisting of the INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT, the INTERLEUKIN-2 RECEPTOR BETA SUBUNIT, and the INTERLEUKIN RECEPTOR COMMON GAMMA-CHAIN.Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends.Graft Survival: The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host.Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.Transplantation Chimera: An organism that, as a result of transplantation of donor tissue or cells, consists of two or more cell lines descended from at least two zygotes. This state may result in the induction of donor-specific TRANSPLANTATION TOLERANCE.Models, Immunological: Theoretical representations that simulate the behavior or activity of immune system, processes, or phenomena. They include the use of mathematical equations, computers, and other electrical equipment.Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.Isoantigens: Antigens that exist in alternative (allelic) forms in a single species. When an isoantigen is encountered by species members who lack it, an immune response is induced. Typical isoantigens are the BLOOD GROUP ANTIGENS.H-Y Antigen: A sex-specific cell surface antigen produced by the sex-determining gene of the Y chromosome in mammals. It causes syngeneic grafts from males to females to be rejected and interacts with somatic elements of the embryologic undifferentiated gonad to produce testicular organogenesis.Lymph Nodes: They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.Stress, Physiological: The unfavorable effect of environmental factors (stressors) on the physiological functions of an organism. Prolonged unresolved physiological stress can affect HOMEOSTASIS of the organism, and may lead to damaging or pathological conditions.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Antigens, CD4: 55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. CD4 antigens are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. CD4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120.Immunosuppression: Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs.Anterior Chamber: The space in the eye, filled with aqueous humor, bounded anteriorly by the cornea and a small portion of the sclera and posteriorly by a small portion of the ciliary body, the iris, and that part of the crystalline lens which presents through the pupil. (Cline et al., Dictionary of Visual Science, 4th ed, p109)Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient.Peripheral Nervous System Diseases: Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.Acclimatization: Adaptation to a new environment or to a change in the old.Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Self Concept: A person's view of himself.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Lymphopenia: Reduction in the number of lymphocytes.Epitopes, T-Lymphocyte: Antigenic determinants recognized and bound by the T-cell receptor. Epitopes recognized by the T-cell receptor are often located in the inner, unexposed side of the antigen, and become accessible to the T-cell receptors after proteolytic processing of the antigen.Mice, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Hypersensitivity, Delayed: An increased reactivity to specific antigens mediated not by antibodies but by cells.Clone Cells: A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)Insulin Resistance: Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS.Interferon-gamma: The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.Immunoconjugates: Combinations of diagnostic or therapeutic substances linked with specific immune substances such as IMMUNOGLOBULINS; MONOCLONAL ANTIBODIES; or ANTIGENS. Often the diagnostic or therapeutic substance is a radionuclide. These conjugates are useful tools for specific targeting of DRUGS and RADIOISOTOPES in the CHEMOTHERAPY and RADIOIMMUNOTHERAPY of certain cancers.Antigens, CD86: A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CD28 ANTIGEN with high specificity and to CTLA-4 ANTIGEN with low specificity. The interaction of CD86 with CD28 ANTIGEN provides a stimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.Antigens, CD95: A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.Sodium Chloride: A ubiquitous sodium salt that is commonly used to season food.Salt-Tolerant Plants: Plants that can grow well in soils that have a high SALINITY.Antigens, CD28: Costimulatory T-LYMPHOCYTE receptors that have specificity for CD80 ANTIGEN and CD86 ANTIGEN. Activation of this receptor results in increased T-cell proliferation, cytokine production and promotion of T-cell survival.Immunomodulation: Alteration of the immune system or of an immune response by agents that activate or suppress its function. This can include IMMUNIZATION or administration of immunomodulatory drugs. Immunomodulation can also encompass non-therapeutic alteration of the immune system effected by endogenous or exogenous substances.Coculture Techniques: A technique of culturing mixed cell types in vitro to allow their synergistic or antagonistic interactions, such as on CELL DIFFERENTIATION or APOPTOSIS. Coculture can be of different types of cells, tissues, or organs from normal or disease states.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Encephalomyelitis, Autoimmune, Experimental: An experimental animal model for central nervous system demyelinating disease. Inoculation with a white matter emulsion combined with FREUND'S ADJUVANT, myelin basic protein, or purified central myelin triggers a T cell-mediated immune response directed towards central myelin. The pathologic features are similar to MULTIPLE SCLEROSIS, including perivascular and periventricular foci of inflammation and demyelination. Subpial demyelination underlying meningeal infiltrations also occurs, which is also a feature of ENCEPHALOMYELITIS, ACUTE DISSEMINATED. Passive immunization with T-cells from an afflicted animal to a normal animal also induces this condition. (From Immunol Res 1998;17(1-2):217-27; Raine CS, Textbook of Neuropathology, 2nd ed, p604-5)Peripheral Vascular Diseases: Pathological processes involving any one of the BLOOD VESSELS in the vasculature outside the HEART.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Receptors, Antigen, B-Cell: IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment.Immunophenotyping: Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort T-lymphocytes into subsets based on CD antigens by the technique of flow cytometry.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Freezing: Liquids transforming into solids by the removal of heat.T-Lymphocytes, Cytotoxic: Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2.Analgesics, Opioid: Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS.Fas Ligand Protein: A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS.Mice, Inbred CBAPlants, Genetically Modified: PLANTS, or their progeny, whose GENOME has been altered by GENETIC ENGINEERING.Salinity: Degree of saltiness, which is largely the OSMOLAR CONCENTRATION of SODIUM CHLORIDE plus any other SALTS present. It is an ecological factor of considerable importance, influencing the types of organisms that live in an ENVIRONMENT.Antigens, CD8: Differentiation antigens found on thymocytes and on cytotoxic and suppressor T-lymphocytes. CD8 antigens are members of the immunoglobulin supergene family and are associative recognition elements in MHC (Major Histocompatibility Complex) Class I-restricted interactions.Mice, Inbred APeptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Gene Expression Regulation, Plant: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in plants.Immunization: Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.Cytotoxicity, Immunologic: The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.Mice, Inbred C3HLymphocyte Depletion: Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation.Lupus Erythematosus, Systemic: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.Leukocytes, Mononuclear: Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.Epitopes: Sites on an antigen that interact with specific antibodies.Cold Temperature: An absence of warmth or heat or a temperature notably below an accustomed norm.Glucose: A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.Muramidase: A basic enzyme that is present in saliva, tears, egg white, and many animal fluids. It functions as an antibacterial agent. The enzyme catalyzes the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrin. EC 3.2.1.17.Lymphoid Tissue: Specialized tissues that are components of the lymphatic system. They provide fixed locations within the body where a variety of LYMPHOCYTES can form, mature and multiply. The lymphoid tissues are connected by a network of LYMPHATIC VESSELS.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Receptors, Antigen, T-Cell, alpha-beta: T-cell receptors composed of CD3-associated alpha and beta polypeptide chains and expressed primarily in CD4+ or CD8+ T-cells. Unlike immunoglobulins, the alpha-beta T-cell receptors recognize antigens only when presented in association with major histocompatibility (MHC) molecules.Diabetes Mellitus, Type 2: A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.T-Lymphocytes, Helper-Inducer: Subpopulation of CD4+ lymphocytes that cooperate with other lymphocytes (either T or B) to initiate a variety of immune functions. For example, helper-inducer T-cells cooperate with B-cells to produce antibodies to thymus-dependent antigens and with other subpopulations of T-cells to initiate a variety of cell-mediated immune functions.Lymphocyte Count: The number of LYMPHOCYTES per unit volume of BLOOD.Desiccation: Removal of moisture from a substance (chemical, food, tissue, etc.).Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Plant Roots: The usually underground portions of a plant that serve as support, store food, and through which water and mineral nutrients enter the plant. (From American Heritage Dictionary, 1982; Concise Dictionary of Biology, 1990)Antigens, CD3: Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA).Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.

*Systemic lupus erythematosus

Kanta H, Mohan C (March 2009). "Three checkpoints in lupus development: central tolerance in adaptive immunity, peripheral ... Neuropsychiatric syndromes can result when SLE affects the central or peripheral nervous system. The American College of ... B and T cell tolerance for apoptotic cells is abrogated, and the lymphocytes get activated by these autoantigens; inflammation ... West SG (September 1996). "Lupus and the central nervous system". Curr Opin Rheumatol. 8 (5): 408-14. doi:10.1097/00002281- ...

*Immune tolerance

Tolerance is classified into central tolerance or peripheral tolerance depending on where the state is originally induced-in ... Central tolerance is the main way the immune system learns to discriminate self from non-self. Peripheral tolerance is key to ... Immune tolerance is formally differentiated into central or peripheral; however, alternative terms such as "natural" or " ... These two methods of categorization are sometimes confused, but are not equivalent-central or peripheral tolerance may be ...

*Outline of immunology

Alloimmunity Cross-reactivity Tolerance Central tolerance Peripheral tolerance Clonal anergy Clonal deletion Tolerance in ... BioMed Central:Immunology is an open access journal publishing original peer-reviewed research articles. Nature Reviews ... Neuroimmune system in the Central nervous system Ocularimmunology - Ocular immune system in the Eye Cancer immunology/ ...

*Clonal anergy

Dominant and recessive tolerance are forms of a peripheral tolerance (the other tolerance beside peripheral is a central ... and consists of a direct induction of peripheral lymphocyte tolerance. An individual in a state of anergy often indicates that ... Similarly to recessive tolerance, unopposed NFAT signalling is also important for T-reg induction. In this case, the NFAT ... Many viruses (HIV being the most extreme example) seem to exploit the immune system's use of tolerance induction to evade the ...

*Somatic hypermutation

Metzger, T.C. (2011). "Control of Central and Peripheral Tolerance by Aire". Immunol Rev. 2011 May. 241 (1): 89-103. doi: ...

*Bcl-2

When it is functional, it can cause immune unresponsiveness to self-antigens via both central and peripheral tolerance. In the ... which leads to aberrant T cell AICD and defective peripheral tolerance. Due to the fact that dendritic cells are the immune ...

*Short course immune induction therapy

Immune tolerance is maintained by central and peripheral tolerance. During central tolerance, T-cells are selected in the ... While autoimmunity is thought to result from the breakdown of central and peripheral tolerance, an undesirable immune responses ... A short, 5-day course of FcR-binding, anti-CD3 antibody treatment was able to re-establish peripheral tolerance in animal ... These strategies employed the use of soluble peptide tolerance and oral peptide tolerance to great efficacy in experimental ...

*Betty Diamond

Diamond's primary interests are in the mechanisms of central and peripheral tolerance of autoreactive B cells, and the defects ... Receptor editing in peripheral B cell tolerance. Proc. Natl. Acad. Sci.102:1608-1613 (2005). Forestier, C., Molano, A., Im, JS ... The immune tolerance network and rheumatic disease: immune tolerance comes to the clinic. Arthritis & Rheumatism 44: 1730 (2001 ... and Diamond, B. Enforced expression of the apoptosis inhibitor Bc1-2 ablates tolerance induction in DNA-reactive B cells ...

*MHC class I

... and CTLs will not be activated in response to them due to central and peripheral tolerance mechanisms. When a cell expresses ... PirB is expressed in the central nervous system and diminishes ocular dominance plasticity in the developmental critical period ...

*Phagocyte

The first type of tolerance is central tolerance, that occurs in the thymus. T cells that bind (via their T cell receptor) to ... The second type of immunological tolerance is peripheral tolerance. Some self reactive T cells escape the thymus for a number ... This process is called tolerance. Dendritic cells also promote immunological tolerance, which stops the body from attacking ... When immunological tolerance fails, autoimmune diseases can follow. Phagocytes of humans and other jawed vertebrates are ...

*Infectious tolerance

Immune tolerance Central tolerance Peripheral tolerance regulatory T cells Immune response Immune tolerance in pregnancy ... Infectious tolerance is a term referring to a phenomenon where a tolerance-inducing state is transferred from one cell ... The goal is to achieve long-term tolerance of the transplant through short-term therapy. The term "infectious tolerance" was ... "Induction of tolerance in peripheral T cells with monoclonal antibodies". European Journal of Immunology. 20 (12): 2737-2745. ...

*T cell receptor revision

Peripheral tolerance is a mechanism controlling such autoreactive T cells in secondary lymphoid organs, blood circulation and ... not controlled by the central tolerance mechanism in the thymus or better eliminate such self-reactive T cells on the other ... Activation-dependent T cell revision process is part of peripheral tolerance mechanisms if the new TCR specificity loses its ... are eliminated in the thymus immediately in a process of central tolerance, however it is not 100% effective again. As a result ...

*Central tolerance

... is distinct from peripheral tolerance in that it occurs while developing immune cells are still present in ... Such regulatory T cells can be considered both central tolerance and peripheral tolerance mechanisms, as they can be generated ... As this tolerance is dependent on encountering self-antigens during maturation, lymphocytes can only develop central tolerance ... Peripheral tolerance). If mature peripheral B cells encounter multivalent antigen (e.g. cell surfaces) they are eliminated via ...

*Peripheral tolerance

... is the second branch of immunological tolerance, after central tolerance. It takes place in the immune ... Dependence of a particular antigen on either central or peripheral tolerance is determined by its abundance in the organism. B ... Mechanisms of peripheral tolerance include direct inactivation of effector T cells by either clonal deletion, conversion to ... Although the majority of self-reactive T cell clones are deleted in the thymus by the mechanisms of central tolerance, low ...

*Traumatic brain injury modeling

... have been conducted in attempts to create a general model for the mechanical tolerance of neurons within the Central Nervous ... One such in vitro model has found that CNS neurons have a lower threshold for stress and strain loads than Peripheral Nervous ...

*Autoimmunity

Tolerance can also be differentiated into "Central" and "Peripheral" tolerance, on whether or not the above-stated checking ... Loss of tolerance by T cells has been extremely hard to demonstrate, and where there is evidence for an abnormal T cell ... Tolerance and Autoimmunity Edwards JC, Cambridge G, Abrahams VM (1999). "Do self perpetuating B lymphocytes drive human ... A puzzling feature of the documented loss of tolerance seen in spontaneous human autoimmunity is that it is almost entirely ...

*Uveitis

December 2003). "An immunologically privileged retinal antigen elicits tolerance: major role for central selection mechanisms ... April 2007). "Limited peripheral T cell anergy predisposes to retinal autoimmunity". J. Immunol. 178 (7): 4276-83. doi:10.4049/ ... Failure of this mechanism leads to neutrophil and other leukocyte recruitment from the peripheral blood through IL-17 secretion ...

*Receptor editing

This process forms part of central tolerance to attempt to change the specificity of the antigen receptor of self reactive ... It is thought that 20-50% of all peripheral naive B cells have undergone receptor editing making it the most common method of ... Halverson R, Torres RM, Pelanda R (2004). "Receptor editing is the main mechanism of B cell tolerance toward membrane antigens ... Meffre, E; Wardemann, H (2008). "B-cell tolerance checkpoints in health and autoimmunity". Current Opinion in Immunology. 20: ...

*Stimulant

... s enhance the activity of the central and peripheral nervous systems. Common effects may include increased alertness, ... Drug tolerance, dependence, and sensitization as well as a withdrawal syndrome can occur. ... Abuse of central nervous system (CNS) stimulants is common. Addiction to some CNS stimulants can quickly lead to medical, ... Amphetamine produces central stimulant, anorectic, and sympathomimetic actions, and it is the prototype member of this class ( ...

*Thymus

Therefore, one of the most important roles of the thymus is the induction of central tolerance. The thymus is largest and most ... Histologically, each lobe of the thymus can be divided into a central medulla and a peripheral cortex which is surrounded by an ... 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 ...

*Harald von Boehmer

Rocha, B. and von Boehmer, H.: Peripheral selection of the T cell repertoire. Science 251, 1225 (1991). Peripheral tolerance by ... 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: ... Tolerance to histocompatibility determinants in tetraparental bone marrow chimeras. J. Exp. Med. 141, 322 (1975). Graft-versus- ...

*Central governor

... the central governor'. Moreover, a variety of peripheral factors in addition to those such as lactic acid build up can impair ... and the tolerance of ischemic pain and power when a tourniqueted hand squeezes a spring exerciser 12 times. The existence of a ... The central governor is a proposed process in the brain that regulates exercise in regard to a neurally calculated safe ... Weir, J. P.; Beck, T. W.; Cramer, J. T.; Housh, T. J. (2006). "Is fatigue all in your head? A critical review of the central ...

*Lymphatic system

Therefore, one of the most important roles of the thymus is the induction of central tolerance. The thymus is largest and most ... The peripheral lymphoid organs are the sites of lymphocyte activation by antigens. Activation leads to clonal expansion and ... The central nervous system also has lymphatic vessels, as discovered by University of Virginia Researchers. The search for T- ... The primary or central lymphoid organs generate lymphocytes from immature progenitor cells. The thymus and the bone marrow ...

*Adipose tissue

This explains to a large degree why central obesity is a marker of impaired glucose tolerance and is an independent risk factor ... Adipose tissue is the greatest peripheral source of aromatase in both males and females,[citation needed] contributing to the ... May 2009) "Central obesity and multivariable cardiovascular risk as assessed by the Framingham prediction scores" Am J Cardiol ... Three regulators of transcription are central to WAT browning and serve as targets for many of the molecules known to influence ...

*Trihexyphenidyl

A specific antagonist is physostigmine which combines a peripheral and a central action. Carbachol can be used to treat atonic ... Tolerance may develop during therapy which requires dose adjustments. Striated musculature and weight gain. Trihexyphenidyl is ... In higher doses direct central inhibition of cerebral motor centers may contribute. In very high doses central toxicity as seen ... Many of these peripheral symptoms, especially considering an acute increase in anxiety with various physical complaints, as ...
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...
Secondary infections are a major complication of sepsis and associated with a compromised immune state, called sepsis-induced immunoparalysis. Molecular mechanisms causing immunoparalysis remain unclear; however, changes in cellular metabolism of leukocytes have been linked to immunoparalysis. We investigated the relation of metabolic changes to antimicrobial monocyte functions in endotoxin-induced immunotolerance, as a model for sepsis-induced immunoparalysis. In this study, immunotolerance was induced in healthy males by intravenous endotoxin (2 ng/kg, derived from Escherichia coli O:113) administration. Before and after induction of immunotolerance, circulating CD14(+) monocytes were isolated and assessed for antimicrobial functions, including cytokine production, oxidative burst, and microbial (Candida albicans) killing capacity, as well metabolic ...
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 ...
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 ...
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 ...
Tregs play a fundamental role in immune tolerance via control of self-reactive effector T cells (Teffs). This function is dependent on maintenance of a high intracellular cAMP concentration. A number of microRNAs are implicated in the maintenance of Tregs. In this study, we demonstrate that peripheral immune tolerance is critically dependent on posttranscriptional repression of the cAMP-hydrolyzing enzyme phosphodiesterase-3b (Pde3b) by microRNA-142-5p (miR-142-5p). In this manner, miR-142-5p acts as an immunometabolic regulator of intracellular cAMP, controlling Treg suppressive function. Mir142 was associated with a super enhancer bound by the Treg lineage-determining transcription factor forkhead box P3 (FOXP3), and Treg-specific deletion of miR-142 in mice (TregΔ142) resulted in spontaneous, lethal, multisystem autoimmunity, despite preserved numbers of phenotypically normal Tregs. ...
microRNA-142-mediated repression of phosphodiesterase 3B critically regulates peripheral immune tolerance.. J Clin Invest. 2019 Feb 11. pii: 124725. doi: 10.1172/JCI124725. [Epub ahead of print]. Anandagoda N, Willis JC, Hertweck A, Roberts LB, Jackson I, G kmen MR, Jenner RG, Howard JK, Lord GM.. Abstract. Tregs play a fundamental role in immune tolerance via control of self-reactive effector T cells (Teffs). This function is dependent on maintenance of a high intracellular cAMP concentration. A number of microRNAs are implicated in the maintenance of Tregs. In this study, we demonstrate that peripheral immune tolerance is critically dependent on posttranscriptional repression of the cAMP-hydrolyzing enzyme phosphodiesterase-3b (Pde3b) by microRNA-142-5p (miR-142-5p). In this manner, miR-142-5p acts as an immunometabolic ...
Short Course Immune Induction Therapy or SCIIT, is a therapeutic strategy employing rapid, specific, short term-modulation of the immune system using a therapeutic agent to induce T-cell non-responsiveness, also known as operational tolerance. As an alternative strategy to immunosuppression and antigen-specific tolerance inducing therapies, the primary goal of SCIIT is to re-establish or induce peripheral immune tolerance in the context of autoimmune disease and transplant rejection through the use of biological agents (compare also tolerogenic therapy). In recent years, SCIIT has received increasing attention in clinical and research settings as an alternative to immunosuppressive drugs currently used in the clinic, drugs which put the patients at risk of developing infection, cancer, and cardiovascular disease. Immune ...
TY - JOUR. T1 - Sinus tachycardia is associated with impaired exercise tolerance following heart transplantation. AU - Peled, Yael. AU - Varnado, Sara. AU - Lowes, Brian D. AU - Zolty, Ronald. AU - Lyden, Elizabeth R.. AU - Moulton, Michael J. AU - Um, John Y. AU - Raichlin, Eugenia. PY - 2017/5. Y1 - 2017/5. N2 - Background: Sinus tachycardia often presents in heart transplantation (HTx) recipients, but data on its effect on exercise performance are limited. Methods: Based on mean heart rate (HR) value 3 months after HTx, 181 patients transplanted from 2006 to 2015 at University of Nebraska Medical Center were divided into two groups: (i) HR,95 beats/min (bpm, n=93); and (ii) HR≥95 bpm (n=88). Cardiopulmonary exercise testing (CPET) was performed 1 year after HTx. Results: Mean HR at 3 months post-HTx was 94±11 bpm and did not change significantly at 1 year post-HTx (96±11 bpm, P=.13). HR≥95 bpm at 3 months was associated with younger donor age (OR 1.1; CI ...
The release of Otto Warmbier, still in an unresponsive state, from North Korean imprisonment has left his family struggling to understand the mysterious circumstances surrounding the 22-year-olds medical condition. He spent at least 17 months in pri…
Molecular mimicry is normally a repeated theme in host defense processes. mannopyranoside inside the antibody paratope exposed multiple modes of binding of the carbohydrate antigen in mAb 2D10 vis vis solitary docking mode in mAb 1H7, which overlapped with the common monosaccharide binding site defined in anti-carbohydrate antibodies. The presence of additional antigen binding modes is perhaps reflective of the utilization of conformational flexibility in molecular mimicry. A relatively broader acknowledgement repertoireattributable to paratope flexibilitymay facilitate the acknowledgement of modified antigens of invading pathogens while the antibodies with thin acknowledgement specificity maintain the fidelity of the response. Intro The hallmark of the acquired immune system is definitely impressive specificity in its acknowledgement repertoire that not merely counters the invading pathogens but also guarantees self-nonself discrimination. Research involving various areas of humoral and mobile ...
Toll Receptors and the Renaissance of Innate Immunity Elizabeth H. Bassett and Tina Rich Overview n the last few pages of Immunology: The Science of Self-Nonself Discrimination Jan Klein ponders on wh
Two percent lidocaine with vasoconstrictor should not provide a key substrate for psychomotor stimulants, opiates, nicotine and mecamylamine on rat immc) (shanahan et al 1981a). Ld50 in mice immunised by cercariae exposed to repeated withdrawals from ethanol. Metabolic imaging studies of autobiographical memory, multiple memories should be given to take place. An upper gastrointestinal tract. Distinct patterns of cognitive neuroscience of attention to stypsis and control of the physiological operation of ige-mediated immediate hypersensitivity responses (e. 6%) 5 (3. The science of self-nonself discrimination, new york academy of sciences usa 93, 8716 8800. Il-6 promotes the formation of bridges between the degree of dissociation appears to be entirely normal during a neuroanatomy laboratory. New york, free press, 1983 christie gl, pawson me: The psychological impact of abuse (see below). Bacci pa. David lewis. Suggesting more cortical surface of the lateral recess of the, the fact that they ...
Most autoreactive T cells are exposed to self-antigen either in the thymus or the periphery, and high avidity T cells are eliminated in both compartments. In contrast, lower avidity T cells are often found in ongoing autoimmune diseases (Bulek et al., 2012) and in anti-tumor responses (McMahan and Slansky, 2007). Thus, expression of a low avidity TCR, allowing autoreactive T cells to bypass elimination, is a major mechanism by which autoreactive T cells escape tolerance (von Herrath et al., 1994; Nugent et al., 2000; Zehn and Bevan, 2006). However, up to this point, we had limited insight into the phenotypic and functional characteristics of these low avidity self-reactive T cells. Thus, it was unclear how self-antigen recognition in the thymus or periphery impacts the function of these T cells and whether such exposure imprinted mechanisms that restrict their activation. The failure to negatively select low avidity self-reactive T cells stimulated us to ...
A paradigm shift in immunology has been the recent discovery of regulatory T cells (T reg cells), of which CD4(+)Foxp3(+) cells are proven as essential to self-tolerance. Using transgenic B6.Foxp3(hCD2) mice to isolate and ablate Foxp3(+) T reg cells with an anti-hCD2 antibody, we show for the first time that CD4(+)Foxp3(+) cells are crucial for infectious tolerance induced by nonablative anti-T cell antibodies. In tolerant animals, Foxp3(+) T reg cells are constantly required to suppress effector T cells still capable of causing tissue damage. Tolerated tissue contains T cells that are capable of rejecting it, but are prevented from doing so by therapeutically induced Foxp3(+) T reg cells. Finally, Foxp3(+) cells have been confirmed as the critical missing link through which infectious tolerance operates in vivo. Peripherally induced ...
The Immune Tolerance Network (ITN) is an international clinical research consortium sponsored by NIAID, part of the National Institutes of Health. Our mission is to accelerate the clinical development of immune tolerance therapies.. Immune tolerance therapies reprogram the immune system in a highly specific manner so that disease-causing immune responses are stopped while maintaining the immune systems ability to combat pathogen infection. The ITN develops and conducts clinical trials and mechanistic studies of specialized immune tolerance therapies in the following areas:. ...
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.. ...
Congenital T cell (T)-deficient mice, such as RAG-1- or SCID mice, succumb to inflammatory bowel disease (IBD) upon adoptive transfer of syngenic naive T cells as a consequence of chronic inflammation in the intestine from unfettered response to commensal bacterial antigens. Although the prevailing view for the onset of IBD is believed to be the absence of regulatory T cells (Tregs), the finding that donor T cells undergo considerable chronic activation even in the presence of Tregs suggests an abnormality in the presentation of enteric antigens also appears to be involved. To study if such a defect is also evident during the lymphopenic neonatal period, we compared the induction of oral tolerance between B6 neonates and adults to host commensal or exogenously provided nominal Ags by adoptively transferring polylconal or Ag-specific donor T cells. Strikingly, donor T cells in neonatal hosts proliferated much faster and more readily acquired effector function ...
The atheroprotective effect paralleled an induction of Treg suppression of apoB-100-specific effector T cells and an increase in IL-10+ CD4+ T cells. Therefore, our data suggest that nasal immunization with p210-CTB protects against atherosclerosis by inducing antigen-specific, IL-10+ regulatory Tr1 cells. It is unlikely that atheroprotection involved the immunosuppressive cytokine TGF-β because nasal immunization with p210-CTB also reduced atherosclerosis in mice lacking a functional TGF-β receptor on T cells.. Antigen-specific as well as antigen-independent effects have been reported in studies of Treg.25 Several studies of autoimmune diseases support the regulation model according to which Treg suppresses conventional effector T cells with the same antigen specificity. Other investigators report that Treg exerts major effects on antigen-presenting cells in an antigen-independent manner. Our data clearly show that antigen-specific atheroprotection was paralleled by inhibition of ...
The administration of antigens into the anterior chamber (AC) of the eye induces a special form of antigen-specific peripheral immune tolerance termed AC-associated immune deviation (ACAID), which prevents delayed-type hypersensitivity (DTH) responses and other inflammatory responses. Type-II collagen (CII) is highly expressed in cartilage tissues and has been linked to Rheumatoid arthritis, aging, and osteoarthritis. To explore the potential for ACAID induction via CII, we checked for different signs of ACAID generation following the AC injection of CII in BALB/c mice. We hypothesized that the mechanism of ACAID induction involves efferent T regulatory cells (Tregs). Both local adoptive transfer (LAT) assays and DTH assays were performed. Results indicated that ACAID induction was driven by the AC injection of CII. Spleen cells of mice injected with CII in the AC significantly suppressed DTH responses. ACAID induction was mediated by ...
Background: Dendritic cells (DCs) are professional antigen-presenting cells able to induce immunity or tolerance. The interactions of immature DCs with naive T lymphocytes induce peripheral tolerance through mechanisms that include anergy or deletion of lymphocytes or the generation of regulatory T cells. Because of the central role of DCs in the immune response, they are potential targets for the induction of experimental tolerance. Thus, the generation of immature (tolerogenic) DCs able to capture and present alloantigens to T cells represents an important aim in our efforts to achieve better transplant acceptance. Methods: In this work, we generated immature DCs by using vitamin D 3 (VD3) during the process of DC differentiation. Results: The VD3DCs showed an immature phenotype characterized by a low expression of major ...
At the present time, heart transplant recipients must take anti-rejection medication to prevent rejection of the donated heart. Even with this medication, chronic rejection is the most common cause of late graft loss. The anti-rejection agents themselves are significantly toxic, with side effects including kidney damage, infection and an increased incidence of cancer. The goal of this study is to allow the patient to develop tolerance to the transplanted heart while maintaining a competent immune system. Tolerance enables the transplant recipients body to recognize the transplanted organ as self rather than foreign tissue. The recipient will not try to reject the donor heart and the need for anti-rejection medication could be dramatically decreased or eliminated entirely. To accomplish this, patients in this study will receive specially treated bone marrow taken from their heart donor. Bone marrow transplant ...
Description of disease T-suppressor cell. Treatment T-suppressor cell. Symptoms and causes T-suppressor cell Prophylaxis T-suppressor cell
To investigate the antigen specificity of regulatory T cells capable of preventing transplant rejection, we have developed two different strategies to achieve tolerance to fully mismatched skin grafts in euthymic mice. A combination of nondepleting Abs targeting CD4, CD8, and CD154 (CD40 ligand) induces dominant transplantation tolerance to fully mismatched skin allografts. Such tolerance is antigen-specific, mediated by regulatory T cells, and can be extended through linked suppression to naïve lymphocytes. The same protocol, when combined with allogeneic bone marrow, enables the development of mixed hematopoietic chimerism and deletional tolerance. Although we cannot exclude that some regulatory T cells may persist in chimeric mice, these cells are insufficient to mediate linked suppression. CD4(+)CD25(+) ...
Attempts were made to break the tolerance of lymph node B cells to deaggregated human gamma globulin. Using allotype-congenic mice, lymph node cells from virgin or tolerant (5 mg) CBA/Igb donors were transferred tonormal CBA/Iga recipients and the proportion of responding donor B cells estimated 1 and 13 days later. The response of the non-tolerant virgin cells diminished with time but was still detectable at 13 days whereas the response of the tolerant cells was tenfold lower than normal cells at day 1 and was not detectable at 13 days. This functional deletion of tolerant cells was not reversed by enzymatic stripping of the immuno-globulin receptors before transfer, nor by removing T cells-which might have had a suppressor action. In other experiments Igb mice were thymectomized or left as controls at various times before tolerance induction. Lymph node cells from these mice were transferred, together with ...
B cell knockout mice microMT/microMT were used to examine the requirement for B cell antigen (Ag) presentation in the establishment of CD4+ T cell tolerance. CD4+T cells from microMT mice injected with exogenous protein Ag in adjuvant responded to in vitro challenge by transcription of cytokine mRNA, cytokine secretion, and proliferation. Peripheral tolerance could be established in microMT mice with a single dose of deaggragated protein. This tolerance was manifested by a loss of T cell proliferation and cytokine production (including both T helper cell type 1 [Th1]- and Th2-related cytokines), indicating that B cells are not required for the induction of peripheral T cell tolerance and suggesting that the dual zone ...
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...
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 ...
Argyris, B F. and Lustro, F D., "Immunologic unresponsiveness of mouse spleen sensitized to allogeneic tumors." (1977). Subject Strain Bibliography 1977. 1705 ...
The tumor immune microenvironment (TIME) is the cellular environment in which tumors exist. This includes: surrounding blood vessels, immune cells, fibroblasts, bone marrow-derived inflammatory cells, lymphocytes, signaling molecules, immune checkpoint proteins and the extracellular matrix (ECM). The TIME plays a critical role in cancer progression and regulation. Tumors can influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the immune cells in the microenvironment can affect the growth and evolution of cancerous cells. The molecules and cells in the TIME influence disease outcome by altering the balance of suppressive versus cytotoxic responses in the vicinity of the tumor. Having a better understanding of the tumor immune microenvironment will pave the way for identifying new targets for immunotherapies that promote cancer elimination.
b,Tolerance and Autoimmunity:,/b, My laboratory explores the fundamental mechanisms of prevention and induction of autoimmune disease of clinical relevance, under four major topics. ,u,First,,/u, we investigate how Ag specific regulatory T cells bearing Foxp3 (Treg) control physiological self tolerance in normal mice. We discovered that regional lymph nodes of normal mice accumulate highly active Treg that suppress autoimmunity of the organ draining to it. We now want to know whether in this strategic location, Treg maintain self tolerance by preventing autoimmune disease triggered by endogenous danger signal. ,u,Second,/u,, we study sperm granuloma in unilaterally-vasectomized mice as endogenous danger signal. Unexpectedly, vx mice develop tolerance to testis Ag, which is terminated by depletion of Treg, ...
Conclusions Apoptosis of epithelial cells leads to translocation of SS-autoantigens and single-stranded hy1-RNA to apoptotic blebs and membrane particles. The apoptotic particles are internalized by pDCs, which in response mature and produce proinflammatory cytokines. Androgens affect to redistribution of autoantigens and diminish the particle-elicited increase of TLR expression in pDCs. Apoptosis of salivary gland cells lead to formation of apoptotic particles, which might affect immunotolerance, production of autoantibodies and onset of autoinflammation. This event might describe how the immunologic tolerance is broken in the early stages of SS. ...
TY - JOUR. T1 - Tolerance induced by inhaled antigen involves CD4+ T cells expressing membrane-bound TGF-β and FOXP3. AU - Ostroukhova, Marina. AU - Seguin-Devaux, Carole. AU - Oriss, Timothy B.. AU - Dixon-McCarthy, Barbara. AU - Yang, Liyan. AU - Ameredes, Bill. AU - Corcoran, Timothy E.. AU - Ray, Anuradha. PY - 2004/7. Y1 - 2004/7. N2 - Under normal circumstances, the respiratory tract maintains immune tolerance in the face of constant antigen provocation. Using a murine model of tolerance induced by repeated exposure to a low dose of aerosolized antigen, we show an important contribution by CD4+ T cells in the establishment and maintenance of tolerance. The CD4+ T cells expressed both cell surface and soluble TGF-β and inhibited the development of an allergic phenotype when adoptively transferred to ...
Incubation of unprimed spleen B cells with high concentrations of hapten-conjugates resulted in the induction of specific unresponsiveness or tolerance to a subsequent encounter with the hapten on a potentially immunogenic carrier. This process of tolerance induction could occur in the absence of extracellular calcium. In contrast B-cell activation to both proliferation and subsequent antibody secretion is known to be calcium dependent. This means that either (1) the decisions which determine immunity and tolerance in B cells are mediated through totally distinct signalling pathways, or that (2) if tolerance and immunity depend on same common signalling events, then the commitment of B cells to switch on or off must be determined at a very early stage.
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While emerging proof indicates that dendritic cells (DC) play a central part in the pathogenesis of multiple sclerosis (MS), their modulation with immunoregulatory providers provides potential customer as disease-modifying therapy. 1,25(Oh yea)2D3-treated DC nor their capability to induce Capital t cell hyporesponsiveness. In addition, the Capital t cell hyporesponsiveness caused by 1,25(Oh yea)2D3-treated DC is definitely antigen-specific and powerful since Capital t cells maintain their capability to react to an unconnected antigen and perform not really reactivate upon rechallenge with completely mature standard DC, respectively. These findings underline the medical potential of tolerogenic DC (tolDC) to right the immunological. ...
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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 ...
Epithelial ovarian cancer (EOC) is certainly a significant cause of cancer-related mortality in women, and there has been zero significant decrease in the death prices credited to EOC in the last 3 decades. into Treg was proven to take place in the growth as a outcome of TGF- IDO or arousal induction [65,66]. Treg generally mediate immunosuppression through cell-cell connections with DC or effector cells or by the release of immunosuppressive cytokines, including IL-10, IL-35 and TGF- [67]. Treg lead to DC tolerization remarkably, further lowering the effector T-cell account activation and growth thus. Strangely enough, association of growth regulatory T-cells with high threat proportion for loss of life and reduced success moments can be presently well noted in EOC Cerovive [23,36,42]. Besides Treg, DC are instrumental in building immunosupression in tumor. While DC had been known as the major orchestrators of the resistant response primarily, their role in the ...
(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
We have used a novel hu-mouse model expressing a human-specific surrogate self-Ag to formally demonstrate that developing human B cells use receptor editing as a mechanism of central B cell tolerance. Central B cell tolerance in hu-mice is stringent but incomplete. Although the selection of autoreactive B cells into the periphery is rare, variations in the extent of tolerance were observed and shown to depend on the amount of self-Ag as well as the individual genetics of the source of CB.. To date, most studies of human B cell tolerance have focused on limited repertoire analyses of B cell subsets present in peripheral blood (Meffre and Wardemann, 2008; Meffre, 2011). These studies have been invaluable in establishing the presence of ...
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 ...
Project ReportCharacterization of micro RNAs (mir 146a, 10a and 34a) involved in the thymic epithelial cell development Autoimmune diseases occur when the body...
The thymic medulla is dedicated for purging the T-cell receptor (TCR) repertoire of self-reactive specificities. Medullary thymic epithelial cells (mTECs) play a pivotal role in this process because they express numerous peripheral tissue-restricted self-antigens. Although it is well known that medulla formation depends on the development of single-positive (SP) thymocytes, the mechanisms underlying this requirement are incompletely understood. We demonstrate here that conventional SP CD4⁺ thymocytes bearing autoreactive TCRs drive a homeostatic process that fine-tunes medullary plasticity in adult mice by governing the expansion and patterning of the medulla. This process exhibits strict dependence on TCR-reactivity with self-antigens expressed by mTECs, as well as engagement of the CD28-CD80/CD86 costimulatory axis. These interactions induce the expression of lymphotoxin α in autoreactive CD4⁺ thymocytes and RANK in mTECs. Lymphotoxin in turn drives mTEC development in synergy with RANKL ...
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 ...
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 ...
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 ...
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 ...
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. ...
... 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. [32], 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 [33], extended these results by modifying the SC isolation method and adding a ...
Copyright 2002 by Katharine Lindner. All rights reserved. # This code is part of the Biopython distribution and governed by its # license. Please see the LICENSE file that should have been included # as part of this package. """ Immune system simulation based on ideas from Immunocomputing: a survey. I.Antoniou, S.Gutnikov, V.Ivanov, Yu.Melnikov, A.Tarakanov 12. Forrest S., Perelson A. Aleen L. and Cherukuri R. Self-nonself disctimination in a computer. Proc. of IEEE symposium on reseqrch in security and privacy. Oakland, USA, 1994, 202-212. Immune system simulation. Accepts an initial set of sequences to be protected. Creates a set of randomly scrambled sequences and uses a lazy check to remove those that trigger on members of the protected set. The detector for a suspicious sequence checks for a close match to a scrambled sequence. The detectors start out with equal weights. When a detector finds a suspicious antigen, its weight is incremented so its chances of being selected in the future ...
TY - JOUR. T1 - The selection of lymphocytes in the thymus. AU - Fabbi, M.. PY - 1995. Y1 - 1995. N2 - The thymus is the main site of T cell maturation. Upon seeding, thymus T cell precursors undergo a complex series of maturational events that involve antigen receptor gene assembly by somatic recombination of gene segments. This process is largely stochastic, therefore a mechanism must exist to shape this antigen receptor repertoire in order to achieve both self restriction (defined as the capacity of a T cell to recognise a peptide antigen in the context of self major histocompatibility complex molecules and self tolerance. This outcome is ensured via selection processes that promote the expansion of those thymocytes that see antigen(s) only in the context of self major histocompatibility gene products. In contrast, those cells that do not fulfill these recognition requirements or that recognise auto antigens with high affinity are deleted. This review ...
CD4+ Foxp3+ regulatory T (Treg) cells belong to a distinct T cell lineage which develops in the thymus and is essential for the prevention of self-reactivity by suppressing peripheral auto-reactive T cells that escape thymic negative selection. IL-2/IL-2R signaling is crucial and non-redundant for the development of thymic Treg cells, as well as the homeostasis and competitive fitness of peripheral Treg cells. The central role of IL-2 in Treg biology is exemplified by the uncontrolled massive lymphoproliferation associated with IL-2-/-, IL-2Rα-/- and IL-2Rβ-/- mice which typically die by 4-12 week of age. It is noteworthy that a restored normal percentage and number of peripheral Treg cells in Bim-/- IL-2-/- mice did not rescue these mice from severe autoimmunity. Instead, additional IL-2 was still required for the proper functioning of peripheral Bim-/- IL-2-/- Treg cells. Consistently, in the current studies, we found that ...
IA-2 is a tyrosine phosphatase-like protein with a single transmembrane (TM) region (residues 577-600) and extracellular and intracellular domains (Fig. 1) (1). IA-2 is enriched in the secretory granules of pancreatic islet cells and neuroendocrine cells, including peptidergic neurons, pituitary cells, and adrenal chromaffin cells (2). It is unclear why the immune system reacts against IA-2 as part of the autoimmune responses associated with type 1 diabetes (3-6). The IA-2 gene is also expressed in the human thymus (7) in a manner similar to other genes coding for self-molecules with tissue-restricted expression, including insulin and glutamic acid decarboxylase (GAD) (7-11), two other autoantigens in type 1 diabetes. Self-antigen expression in thymus may play a key role in promoting immunological self-tolerance, and variation in such expression may have dramatic effects on tolerance. We have also obtained ...
Title: IMMUNOLOGICAL SELF-TOLERANCE MAINTAINED BY ACTIVATED T-CELLS EXPRESSING IL-2 RECEPTOR ALPHA-CHAINS (CD25) - BREAKDOWN OF A SINGLE MECHANISM OF SELF-TOLERANCE CAUSES VARIOUS AUTOIMMUNE- ...
52. Sakaguchi S, Sakaguchi N, Shimizu J, Yamazaki S, Sakihama T, Itoh M, Kuniyasu Y, Nomura T, Toda M, Takahashi T. Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance. Immunol Rev. 2001;182:18-32. 53. Takahashi T, Sakaguchi S. Naturally arising CD25+CD4+ regulatory T cells in maintaining immunologic self-tolerance and preventing autoimmune disease. Curr Mol Med. 2003;3(8):693-706. 54. Afzali B, Lombardi G, Lechler RI, Lord GM. 36. Hayashi H, Maeda M, Murakami S, Kumagai N, Chen Y, Hatayama T, Katoh M, Miyahara N, Yamamoto S, Yoshida Y, Nishimura Y, Kusaka M, Fujimoto W, Otsuki T. Soluble interleukin-2 receptor as an indicator of immunological disturbance found in silicosis patients. Int J Immunopathol Pharmacol. 2009;22(1):53-62. 37. Kabelitz D, ...
Programmed death-1 (PD-1) is a receptor on T cells that has been shown to suppress activating signals from the T cell receptor when bound by either of its ligands, Programmed death-ligand 1 (PD-L1) or PD-L2. When PD-1 expressing T cells contact cells expressing its ligands, functional activities in response to antigenic stimuli, including proliferation, cytokine secretion, and cytotoxicity are reduced. PD-1/PD-Ligand interactions down regulate immune responses during resolution of an infection or tumor, or during the development of self tolerance.. Interference with the PD-1/PD-L1 interaction has also shown enhanced T cell activity in chronic infection systems. Chronic lymphocytic chorio meningitis virus infection of mice also exhibits improved virus clearance and restored immunity with blockade of PD-L1.. In addition to enhancing immunologic responses to chronic antigens, blockade of the PD-1/PD-L1 pathway has also been shown to enhance responses to ...
First described in 1973 by Ralf Steinman, dendritic cells have since attracted considerable attention. Their properties of antigen capture, presentation and T cell activation, place them both as a key bridge between the innate and adaptive immunity, as well as a switch between tolerance and immunity. Although, the human and mouse DC network share many similarities, one subset was discovered in mouse that had not yet found its equivalent in human: the CD8+ DC characterised by their ability produce IL-12, but most particularly to uptake dead cells and "cross-present" these exogenous antigens on MHC class I molecules. This function has been shown to be essential in the immune defense against many viruses, intracellular bacteria and tumors as well as for the maintenance of self tolerance. Four studies in J. Exp. Med provide insight into a potential human homologue to the mouse cross-presentation specialist CD8+ ...
The developmental pathway that TCRαβ+CD8αα+ intestinal intraepithelial lymphocytes (here called unconventional iIEL) follow has long remained a mystery. In their recent paper, McDonald et al. cloned and forced the expression of TCRs isolated from unconventional iIEL and came to the following conclusions. First, TCR specificity drives commitment to the unconventional iIEL lineage. Second, iIEL TCRs induce a pattern of thymic negative selection, with most cells expressing these TCR undergoing apoptosis but a small proportion of them escaping deletion and selectively maturing into unconventional iIEL. Third, the post-selection precursors to unconventional iIEL are the CD4loCD8lo(DPlo)CD69hiPD-1hi thymocytes, a population that largely overlaps with the general pool of MHC class I- or MHC class II-autoreactive thymocytes that undergo negative selection. By downregulating the expression of both CD4 and CD8b coreceptors, these cells largely lose their ability to recognize self ligands and, instead ...
Autoimmune regulator (Aire) is a transcriptional regulator of peripheral tissue antigens (PTAs) and microRNAs (miRNAs) in medullary thymic epithelial cells (mTECs). In this study, we tested the hypothesis that Aire also played a role as an upstream posttranscriptional controller in these cells and that variation in its expression might be associated with changes in the interactions between miRNAs and the mRNAs encoding PTAs. We demonstrated that downregulation of Aire in vivo in the thymuses of BALB/c mice imbalanced the large-scale expression of these two RNA species and consequently their interactions. The expression profiles of a large set of mTEC miRNAs and mRNAs isolated from the thymuses of mice subjected (or not) to small-interfering (siRNA)-induced Aire gene knockdown revealed that 87 miRNAs and 4,558 mRNAs were differentially expressed. The reconstruction of the miRNA-mRNA interaction networks demonstrated that interactions between these RNAs were under Aire influence and therefore ...
After receiving my Ph.D. studying the structure and function of eukaryotic genes, I chose to focus my research career in the field of Immunology. During my postdoctoral fellowship with Dr. Malcolm Gefter at MIT, I made important contributions to our understanding of the genetic basis for development of antibody diversity during primary and antigen-driven B cell development. My main research interest since that time has been to elucidate the molecular and cellular basis for immune memory and self tolerance in the B cell compartment. My laboratory has extensive utilized mouse model systems and mouse reversed genetics approaches to address these questions for over 25 years. In recent years, we have concentrated on the role of the germinal center in the antigen receptor diversification and selection events that culminate in the development of the memory B cell compartment. To begin to translate the discoveries we have made in mouse model systems to a better ...
Based on their ontogeny, tissue localization and functional specialization, monocyte-derived cells exhibit diverse phenotypic and functional properties. Monocyte-derived macrophages (moMAC) and dendritic cells (moDC) differentiate from common precursors in situ but carry out different regulatory functions in the periphery and the central nervous system (CNS). Under pathological conditions both moMACs and moDCs are known to be involved in inflammatory processes of the brain. The primary role of moDCs is to maintain self tolerance in the periphery as well as in the CNS and their subtypes and subsets are specialized for unique functional activities thus playing a pivotal role in bridging innate and adaptive immunity, orchestrating strictly controlled immune responses, and ensure restoration of the resting state or support the generation of regulatory, effector and memory T-lymphocytes. Depending on environmental cues, macrophages can be ...
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CD30 is a type I transmembrane glycoprotein of the TNF receptor superfamily. CD30 was originally identified as a cell surface antigen of Hodgkins and Reed-Sternberg cells using monoclonal antibody Ki-1. The ligand for CD30 is CD30L (CD153). The binding of CD30 to CD30L mediates pleiotropic effects including cell proliferation, activation, differentiation, and apoptotic cell death. CD30 has a critical role in the pathophysiology of Hodgkins disease and other CD30+ lymphomas. CD30 acts as a costimulatory molecule in thymic negative selection. In addition to its expression on Hodgkins and Reed-Sternberg cells, CD30 is also found in some non-Hodgkins lymphomas (including Burkitts lymphomas), virus-infected T and B cells, and on normal T and B cells after activation. In T cells, CD30 expression is present on a subset of T cells that produce Th2-type cytokines and on CD4+/CD8+ thymocytes that co-express CD45RO and the IL4 receptor. Soluble form of CD30 (sCD30) serves as a marker reflecting Th2 ...
antibody-antibodies.com is the marketplace for research antibodies. Find the right antibody for your research needs. Dependence of self-tolerance on TRAF6-directed development of thymic stroma.
The Division of Cancer Immunology aims at identifying novel strategies that can tip the balance to augmenting anti-tumor immune responses by focusing on anti-tumor immune responses and their suppressive mechanisms in a tumor microenvironment. Regulatory T (Treg) cells, actively engaged in the maintenance of immunological self-tolerance and homeostasis, are present in tumor tissues with higher frequencies compared with the periphery and inhibit the development of effective anti-tumor immune responses. We are now investigating the detailed mechanisms of Treg-cell infiltration/proliferation in tumor tissues to control them for a novel target of cancer immunotherapy.. ...
Autoantigenic peptides resulting from self-proteins such as proinsulin are important players in the development of type 1 diabetes mellitus (T1D). Self-proteins can be processed by cathepsins (Cats) within endocytic compartments and loaded to major h
The thymic epithelium forms specialized niches to enable thymocyte differentiation. While the common epithelial progenitor of medullary and cortical thymic epithelial cells (mTECs and cTECs) is well defined, early stages of mTEC lineage specification have remained elusive. Here, we utilized in vivo targeting of mTECs to resolve their differentiation pathways and to determine whether mTEC progenitors participate in thymocyte education. We found that mTECs descend from a lineage committed, podoplanin (PDPN)-expressing progenitor located at the cortico-medullary junction. PDPN(+) junctional TECs (jTECs) represent a distinct TEC population that builds the thymic medulla, but only partially supports negative selection and thymocyte differentiation. Moreover, conditional gene targeting revealed that abrogation of alternative NF-κB pathway signaling in the jTEC stage completely blocked mTEC development. Taken together, this study identifies jTECs as lineage-committed mTEC progenitors and shows that ...
Medullary thymic epithelial cells (mTECs) are critical in establishing and maintaining the appropriate microenvironment for negative selection and maturation of immunocompetent T cells with a self-tolerant T cell antigen receptor repertoire. Cues that direct proliferation and maturation of mTECs are provided by members of the tumor necrosis factor (TNF) superfamily expressed on developing thymocytes. Here we demonstrate a negative role of the morphogen TGF-β in tempering these signals under physiological conditions, limiting both growth and function of the thymic medulla. Eliminating TGF-β signaling specifically in TECs or by pharmacological means increased the size of the mTEC compartment, enhanced negative selection and functional maturation of medullary thymocytes as well as the production of regulatory T cells, thus reducing the autoreactive potential of peripheral T cells.
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 ...
Funding The authors wish to acknowledge the support of the IMI JU-funded project BeTheCure (contract no. 115142-2) and Pfizer (code: RA-IMI-037). LAT was financially supported by a VIDI grant from NWO-Zon-MW. RT was financially supported by a VICI grant from NWO-Zon-MW. JSD was financially supported by the Dutch Arthritis Foundation (project no. 13-3-401). MH (who is an employee of Pfizer) has been involved in technical discussions and scientific collaboration. The funders had no final role in study design, data collection and analysis, decision to publish or preparation of the manuscript. ...
Cortical (cTEC) and medullary (mTEC) thymic epithelial cells establish key microenvironments for T-cell differentiation and arise from thymic epithelial cell progenitors (TEP). However, the nature of TEPs and the mechanism controlling their stemness in the postnatal thymus remain poorly defined. Using TEC clonogenic assays as a surrogate to survey TEP activity, we found that a fraction of cTECs generates specialized clonal-derived colonies, which contain cells with sustained colony-forming capacity (ClonoTECs). These ClonoTECs are EpCAM+MHCII-Foxn1lo cells that lack traits of mature cTECs or mTECs but co-express stem-cell markers, including CD24 and Sca-1. Supportive of their progenitor identity, ClonoTECs reintegrate within native thymic microenvironments and generate cTECs or mTECs in vivo. Strikingly, the frequency of cTECs with the potential to generate ClonoTECs wanes between the postnatal and young adult immunocompetent thymus, but it is sustained in alymphoid Rag2-/-Il2rg-/- counterparts. ...
Danzl, Nichole M., Laura T. Donlin, and Konstantina Alexandropoulos. "Regulation of medullary thymic epithelial cell differentiation and function by the signaling protein Sin." The Journal of Cell Biology 189.3 (2010): i8. Web. 17 Feb. 2018. ...
Results 66 recombinant antibodies were generated from naïve B cells of 4 SS patients and compared to 45 clones from 2 HD. Analysis of the VH and VL gene usage showed no significant differences between SS and HD. Conversely, we observed accumulation of circulating autoreactive naïve B cells in SS as demonstrated by increased reactivity towards Hep2 cells (43.1% SS vs 25% HD) and ENA (19.6% SS clones vs none). Among ENA+ clones, 6 displayed reactivity towards Ro/SSA and/or La/SSB.. ...
Tolerance induction to self antigens in the peripheral lymphoid tissues: blood, lymph nodes, spleen, and mucosal-associated lymphoid tissues.
The clinical heterogeneity of the more than 80 autoimmune diseases presents a significant challenge with respect to the development of therapies designed to re-establish self-tolerance. The ITNs approach to tolerance in autoimmune diseases attempts to address these challenges through a coordinated program of clinical studies aimed at establishing proof-of-principle either in diseases where a self-antigen has been identified, the target organ is accessible for further study or the disease pathogenesis has been relatively well established. Given the complex nature of these diseases, and following the approaches being developed in the transplant and allergy portfolios, the ITN builds on results from ongoing trials by developing combination approaches affecting humoral and cellular, as well as adaptive and innate, immune responses. This includes combinations that ablate or anergize effector responses, deviate ...
Few immunogenic proteins have been identified for immunologic interventions in CRC. Furthermore, the biologic relevance of some of the most commonly exploited antigens in CRC, such as MUC-1 and CEA, is not well elucidated (13,14,16). Data presented here shows that existing microarray datasets provide a rapid method to identify genes upregulated in adenomas that maintain increased expression in carcinomas and that these genes encode proteins that are overexpressed in both adenoma and CRC. Silencing adenoma-CRC gene expression with siRNA in multiple cell lines suggests these proteins may impact cell viability, proliferation, and survival across all CRC phenotypes. Finally, we show that overexpressed proteins conserved from adenoma to CRC have the potential to stimulate an adaptive immune response in either control donors or CRC patients. This latter observation suggests that tolerance has been circumvented to these self-proteins and that boosting immunity ...
In a healthy individual, the immune system uses several different immune tolerance mechanisms in order to prevent the development of autoimmune disease. For T c...
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Dr Gray said one way your body protects against autoimmune disease is definitely by forcing most self-reactive immune cells to die throughout their development. If any self-reactive cells manage to reach maturity, your body normally has a second safeguard of switching these harmful cells into an inactive condition potentially, preventing them from causing autoimmune disease, he stated. Until now, theres been debate about how exactly important the death of self-reactive cells is really as a protection against autoimmune illnesses. Our research has determined two molecules that are needed for this process.This finding suggests that dogs might be an improved pet model for type 1 diabetes than rodents, the authors added. Dr. Joel Zonszein is director of the clinical diabetes middle at Montefiore INFIRMARY in NEW YORK. He stated, Although diabetes in the dog resembles type 1 in human beings, they dont have got the same inflammatory process we observe in type 1 in human beings. In dogs, we hardly ...
Bugs item #1178872, was opened at 2005-04-07 17:20 Message generated for change (Comment added) made by tjreedy You can respond by visiting: https://sourceforge.net/tracker/?func=detail&atid=105470&aid=1178872&group_id=5470 Category: Tkinter Group: Python 2.4 ,Status: Deleted ,Resolution: Duplicate Priority: 5 Submitted By: Emil (droun) Assigned to: Martin v. Löwis (loewis) Summary: Variable.__init__ uses self.set(), blocking specialization Initial Comment: in class Variable the constructor uses self.set() to set the value of the variable. This makes it hard and in some cases impossible to make a speciallization of Variable that performs some operation after changing the value. It would be preferable to use Tkinter.Variable.set(self, self._default) example: class ViewChanger(Tkinter.StringVar) : def __init__(self, views) : self.views = views Tkinter.StringVar.__init__(self) def set(self, newview) : self.views.activate(newview) Tkinter.StringVar.set(newview) get() and everything else will use ...
Regulatory CD4+CD25+ T (Treg) cells play a central role in the maintenance of immune self-tolerance and homeostasis. Although Treg cells operate through multiple mechanisms, it appears that the expression of the transcription ...
While the self is comprised of a long list of mental and physical features, the true self is primarily moral. Moral features contribute to perceived identity more than any other personal feature [1,2]. Moral traits are also considered to be the most deeply rooted, causally central aspect of a persons identity [3]. This pattern is quite robust. It shows up regardless of the context (changes brought on the aging process, medical interventions, supernatural events), and regardless of the type of moral feature (disposition, behavior, or belief); [4,5]).. The true self is not merely moral, but morally good. When asked which part of the self is responsible for a person becoming bad (e.g. a deadbeat dad), subjects attribute this change to the surface self, but becoming a better person (e.g. a loving father) is attributed to the true self [6]. This effect is contingent on the values of the person rendering the judgment: liberals think homosexual urges are part of the true self, but conservatives ...
Besides the cause of weight problems and relevant metabolic and immune-ailments, it has been proposed for BPA a part in the reduction of self-tolerance,
how can I say it, if not timidly like this: life is it self my self. Life is it self my self, and I dont understand what I say. And then I adore. -C.L.
self hatred - MedHelps self hatred Center for Information, Symptoms, Resources, Treatments and Tools for self hatred. Find self hatred information, treatments for self hatred and self hatred symptoms.
When this was said, Citta the elephant trainers son said to the Blessed One: "When there is a gross acquisition of a self, is it the case then that ones mind-made acquisition of a self and formless acquisition of a self are null & void, and only ones gross acquisition of a self is true? And when there is a mind-made acquisition of a self, is it the case then that ones gross acquisition of a self and formless acquisition of a self are null & void, and only ones mind-made acquisition of a self is true? And when there is a formless acquisition of a self, is it the case then that ones gross acquisition of a self and mind-made acquisition of a self are null & void, and only ones formless acquisition of a self is true ...
Japanese drugmaker Astellas and Swiss biotech Anokion have hooked up in a deal worth $760 million to create a new US-based firm focused on developing novel immune tolerance therapeutics. - News - PharmaTimes
Do you know the difference? I was confused for a long time and felt guilty when ever I would practice self care thinking I was being self indulgent! I was far from wrong. The definition of self care is Self Care - Actions and attitudes which...
We hear endless amounts about zero tolerance for drugs and drink driving, how about zero tolerance for violent men? Please tell me what does zero tolerance mean?????
I purchased an 8310 from at&t the other day and I am having a problem with the screen turning if self on intermittently. It seems that for no good reason the screen will just turn on and take awhile to turn it self off. I changed the Backlight timeout to 10 sec but the screen still comes on by it self after awhile. This is becoming quite a drain on the battery. I just switched from an 8703e on Verizon and never had a promblem like this. I have searched this forum, but still can t come up
What is self control?Self control is the ability to control ones feelings, emotions, impulses, and reactions. Effects of self control are seen everywhere, you can ...
... will publish up-to-date, structured reviews on diverse topics in autoimmunity, written by first-class experts in the field. The...
Answer to Describe how the cells of the acquired-immunity system develop so that they do not recognize self-antigens but do recognize foreign antigens.
My treatment centre said that Self-Esteem is what we think of ourselves..Self Worth is how we feel about ourselves..I think I got that right..so, positive thinking.....
Hotcourses has 122 of the best Self Development courses & professionally qualified Brent training - Start the top Self Development courses today
Swinging appears to be on the rise, and it might be happening right next door. SELF reports on whether it revives or ruins relationships.
Got runners trots? Heres why running makes you poop, and what you can do to control it, or prevent it from happening in the first place.
Stadniks growth spurt started at age 14 after a brain operation apparently stimulated his pituitary gland, which produces the human growth hormone.

Myelin-reactive T cells have been identified in individuals with multiple sclerosis - Heat Shock Proteins & Heat Shock ResponseMyelin-reactive T cells have been identified in individuals with multiple sclerosis - Heat Shock Proteins & Heat Shock Response

host disease (20 21 and MS (22). However defects in peripheral tolerance mechanisms alone do not explain the pathology of MS in ... is thought to be an autoimmune disease where activated myelin-reactive T cells migrate into the central nervous system (CNS) ... deficient mice developed a normal Th17 response in peripheral lymphoid organs but failed to develop EAE (17-19). Additionally ...
more infohttp://neuroart2006.com/?p=1207

JCI Insight -
Combination central tolerance and peripheral checkpoint blockade unleashes antimelanoma immunityJCI Insight - Combination central tolerance and peripheral checkpoint blockade unleashes antimelanoma immunity

Moreover, pharmacologic blockade of central T cell tolerance and peripheral checkpoint blockade in combination enhanced ... Together, these findings suggest that Aire-mediated central tolerance constrains the efficacy of peripheral checkpoint ...
more infohttps://insight.jci.org/articles/view/93265/pdf

T-cell tolerance: central and peripheral.  - PubMed - NCBIT-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 ... Recent advances in mechanistic studies of central and peripheral T-cell tolerance are promoting the development of therapeutic ... Cell types in central tolerance. (Top) T cells are positively selected in the thymic cortex. Negative selection via clonal ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/22661634

JCI Insight -
Combination central tolerance and peripheral checkpoint blockade unleashes antimelanoma immunityJCI 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 ... Moreover, pharmacologic blockade of central T cell tolerance and peripheral checkpoint blockade in combination enhanced ... Together, these findings suggest that Aire-mediated central tolerance constrains the efficacy of peripheral checkpoint ... Central T cell tolerance mechanisms protect against the development of autoimmunity, but also limit antitumor immunity (9-11). ...
more infohttps://insight.jci.org/articles/view/93265

Induction of Tolerance: Overview, Central (Intrathymic) Mechanisms of Tolerance, Peripheral (Nonthymic) Mechanisms of ToleranceInduction of Tolerance: Overview, Central (Intrathymic) Mechanisms of Tolerance, Peripheral (Nonthymic) Mechanisms of Tolerance

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 [33] (from Latin prope "near") or minimal immunosuppression tolerance. ...
more infohttps://emedicine.medscape.com/article/430449-overview

B cell signalling in mechanisms of central and peripheral tolerance  - Enlighten: ThesesB 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 ... Hence during B cell development, a number of central and peripheral developmental checkpoints ensure the deletion of self- ... 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. ...
more infohttp://theses.gla.ac.uk/1375/

Ex-vivo expanded DC induce donor-specific central and peripheral tolerance and prolong the acceptance of donor skin allograftsEx-vivo expanded DC induce donor-specific central and peripheral tolerance and prolong the acceptance of donor skin allografts

... 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 ... 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 ...
more infohttps://www.garvan.org.au/research/publications/10946

PPT - Molecular mechanisms of immune tolerance Central tolerance induction in the B cell and T cell compartment Immune toleran...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 ... Peripheral naive CD4+ T cell precursor cells (THp) can differentiate into three subsets of effector T cells (TH1, TH2 and TH-17 ... 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 ...
more infohttps://www.slideserve.com/gene/molecular-mechanisms-of-immune-tolerance-central-tolerance-induction-in-the-b-cell-and-t-cell-compartment-immune-toleran

Central and Peripheral Autoantigen Presentation in Immune Tolerance - PubMedCentral 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 ... and peripheral lymphoid tissues suggests that they may play a role in insulin presentation in both the central and peripheral ...
more infohttps://pubmed.ncbi.nlm.nih.gov/15027898/

Keystone Symposia | Scientific Conferences on Biomedical and Life Science TopicsKeystone Symposia | Scientific Conferences on Biomedical and Life Science Topics

Combinatorial Defects in Central and Peripheral Tolerance Checkpoints Precipitate Autoimmune Pancreatitis and Sialadenitis. ... Specific Issues: • Translating results from studies of animal models to human studies • Peripheral and central tolerance • T ... Short Talk: Lymphatic Endothelial Cells Mediate CD8+ T Cell Peripheral Tolerance by Direct Antigen Presentation that is ... Elegant studies of central T and B cell tolerance have been performed, leading to the identification of multiple mechanisms ...
more infohttps://www.keystonesymposia.org/index.cfm?e=web.Meeting.Program&meetingid=1048

Keystone Symposia | Scientific Conferences on Biomedical and Life Science TopicsKeystone Symposia | Scientific Conferences on Biomedical and Life Science Topics

Combinatorial Defects in Central and Peripheral Tolerance Checkpoints Precipitate Autoimmune Pancreatitis and Sialadenitis. ... Specific Issues: • Translating results from studies of animal models to human studies • Peripheral and central tolerance • T ... Short Talk: Lymphatic Endothelial Cells Mediate CD8+ T Cell Peripheral Tolerance by Direct Antigen Presentation that is ... Elegant studies of central T and B cell tolerance have been performed, leading to the identification of multiple mechanisms ...
more infohttp://keystonesymposia.org/index.cfm?e=web.Meeting.Program&meetingid=1048

Keystone Symposia | Scientific Conferences on Biomedical and Life Science TopicsKeystone Symposia | Scientific Conferences on Biomedical and Life Science Topics

Mechanisms of Peripheral and Central Tolerance Meeting has ended...abstracts no longer viewable online. ... While significant progress has been made in understanding the basic processes of both central and peripheral tolerance, the ... MicroRNA Regulation of Thymic Epithelial Cell Biology and Central Tolerance. Yong Fan, University of Pittsburgh, USA ID-TEC and ... Short Talk: The Type 1 Diabetes-Associated Gene CLEC16A Modulates Thymic Epithelial Cell Function and Impacts Central Tolerance ...
more infohttp://keystonesymposia.org/index.cfm?e=Web.Meeting.Program&MeetingID=1217&pTime=ampm

Anderson MS[au] - PubMed - NCBIAnderson MS[au] - PubMed - NCBI

Citations may include links to full-text content from PubMed Central and publisher web sites. ... Combination central tolerance and peripheral checkpoint blockade unleashes antimelanoma immunity.. Bakhru P, Zhu ML, Wang HH, ... Pulling RANK on Cancer: Blocking Aire-Mediated Central Tolerance to Enhance Immunotherapy. ... Tolerance checkpoint bypass permits emergence of pathogenic T cells to neuromyelitis optica autoantigen aquaporin-4. ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed?cmd=search&term=Anderson+MS%5Bau%5D&dispmax=50

Systemic lupus erythematosus - WikipediaSystemic lupus erythematosus - Wikipedia

Kanta H, Mohan C (March 2009). "Three checkpoints in lupus development: central tolerance in adaptive immunity, peripheral ... Neuropsychiatric syndromes can result when SLE affects the central or peripheral nervous system. The American College of ... West SG (September 1996). "Lupus and the central nervous system". Curr Opin Rheumatol. 8 (5): 408-14. doi:10.1097/00002281- ... B and T cell tolerance for apoptotic cells is abrogated, and the lymphocytes get activated by these autoantigens; inflammation ...
more infohttps://en.wikipedia.org/wiki/Systemic_lupus_erythematosus

Frontiers | Plasmacytoid dendritic cells: development, functions, and role in atherosclerotic inflammation | PhysiologyFrontiers | Plasmacytoid dendritic cells: development, functions, and role in atherosclerotic inflammation | Physiology

2012). Plasmacytoid dendritic cells transport peripheral antigens to the thymus to promote central tolerance. Immunity 36, 338- ... Like cDCs, thymic pDCs acquire advanced ability to endocytose, process, and present peripheral antigens to central tolerance. ... Tregs and promoting central tolerance. TSLP-activated pDCs produce chemokines CCl17 and CCL21 essential for attraction of ... from naïve T cells responsible for maintaining peripheral tolerance. pDC also imprint specific homing properties on T cells ...
more infohttps://www.frontiersin.org/articles/10.3389/fphys.2014.00279/full

The Role of Autoimmune Regulator (AIRE) in Peripheral Tolerance. - Free Online LibraryThe Role of Autoimmune Regulator (AIRE) in Peripheral Tolerance. - Free Online Library

... in Peripheral Tolerance. by Journal of Immunology Research; Health, general Antigens Autoimmunity Gene mutation T cells ... In summary, similar to central tolerance, peripheral DCs that express AIRE can regulate peripheral tolerance through two ... Through the peripheral expression of different TSA groups, eTACs can lead to the tolerance of central antigen specific T cells ... The peripheral functions of AIRE may even be more diverse than its central functions are. First, the types of peripheral ...
more infohttps://www.thefreelibrary.com/The+Role+of+Autoimmune+Regulator+

Frontiers | Precise Delineation and Transcriptional Characterization of Bovine Blood Dendritic-Cell and Monocyte Subsets |...Frontiers | Precise Delineation and Transcriptional Characterization of Bovine Blood Dendritic-Cell and Monocyte Subsets |...

Plasmacytoid dendritic cells transport peripheral antigens to the thymus to promote central tolerance. Immunity (2012) 36:438- ... Steady-state entry into lymph nodes may be important in regard to peripheral tolerance induction (67, 68). In terms of central ... Iberg CA, Jones A, Hawiger D. Dendritic cells as inducers of peripheral tolerance. Trends Immunol. (2017) 38:793-804. doi: ... Grage-Griebenow E, Flad HD, Ernst M. Heterogeneity of human peripheral blood monocyte subsets. J Leukoc Biol. (2001) 69:11-20. ...
more infohttps://www.frontiersin.org/articles/10.3389/fimmu.2018.02505/full

others  Flashcards by Anthos Christofides | Brainscapeothers Flashcards by Anthos Christofides | Brainscape

central tolerance tolerance to self antigens within tha thymus peripheral tolerance tolerance acquired outside the ... in the peripheral lymphoid organs (such as spleen and lymph nodes) where it contributes to peripheral tolerance ... and very high or very low doses of antigens may result in tolerance) ...
more infohttps://www.brainscape.com/flashcards/others-5178666/packs/7620266

Thymic Dendritic Cell Subsets Display Distinct Efficiencies and Mechanisms of Intercellular MHC Transfer | The Journal of...Thymic Dendritic Cell Subsets Display Distinct Efficiencies and Mechanisms of Intercellular MHC Transfer | The Journal of...

Plasmacytoid dendritic cells transport peripheral antigens to the thymus to promote central tolerance. Immunity 36: 438-450. ... peripheral SIRPα+ cDC and pDC laden with self-antigen migrate to the thymus and contribute to central tolerance (13-15). ... Central tolerance to tissue-specific antigens mediated by direct and indirect antigen presentation. J. Exp. Med. 200: 1039-1049 ... T cell central tolerance entails both clonal deletion of thymocytes expressing TCR with increased affinity for self-antigen, ...
more infohttp://www.jimmunol.org/content/198/1/249

The Plasmacytoid Dendritic Cell as the Swiss Army Knife of the Immune System: Molecular Regulation of Its Multifaceted...The Plasmacytoid Dendritic Cell as the Swiss Army Knife of the Immune System: Molecular Regulation of Its Multifaceted...

Plasmacytoid dendritic cells transport peripheral antigens to the thymus to promote central tolerance. Immunity 36: 438-450. ... pDC contribute to peripheral T cell tolerance in transplantation (70), tumor escape (71), oral tolerance (72), and mucosal ... correlating with reduced ability to prime tolerance (74). In humans, a similar tolerance-inducing pDC subset has yet to be ... Tolerance. In the immature state, pDC have a poor ability to support T cell proliferation (67) and even suppress T cell ...
more infohttp://www.jimmunol.org/content/193/12/5772

A novel isoform of the Ly108 gene ameliorates murine lupus | JEMA novel isoform of the Ly108 gene ameliorates murine lupus | JEM

Three checkpoints in lupus development: central tolerance in adaptive immunity, peripheral amplification by innate immunity and ... Although activation of both T and B cells was affected by the presence of Ly108-H1, we focused on the role of peripheral CD4+ T ... Regulation of B cell tolerance by the lupus susceptibility gene Ly108. Science. 312:1665-1669. doi:10.1126/science.1125893. ... Sle1 on murine chromosome 1 leads to a selective loss of tolerance to H2A/H2B/DNA subnucleosomes. J. Clin. Invest. 101:1362- ...
more infohttp://jem.rupress.org/content/208/4/811

PP of Autoimmune Diseases Flashcards by  | BrainscapePP of Autoimmune Diseases Flashcards by | Brainscape

central tolerance: elimination of self-reactive T cells and B cells in central lymphoid organs. - peripheral tolerance:. some ... central tolerance failure, peripheral tolerance failrure. - molecular mimicry. - abnormal presentation of self ags. - epitope ... peripheral activation of T cells requires 2 signals -. recognition of peptide Ag w/ MHCs on the APCs and secondary ... loss of self tolerance w/ development of autoabs is characteristic of number of autoimmune disease: hyperthyroidism in graves ...
more infohttps://www.brainscape.com/flashcards/pp-of-autoimmune-diseases-5240174/packs/7744300

Plus itPlus it

CENTRAL AND PERIPHERAL TOLERANCE. The concept of breaking of tolerance is fundamental to the development of autoimmunity. The ... it has been proposed that tolerance to such proteins can only be achieved through mechanisms of peripheral tolerance. Indeed, ... Peripheral tolerance occurs in secondary lymphoid organs (i.e., lymph nodes and spleen) and regulates the activation of naïve T ... These observations underline the importance of central tolerance in controlling the generation of autoimmunity. ...
more infohttps://diabetes.diabetesjournals.org/content/57/11/2872

IRF4 Deficiency Abrogates Lupus Nephritis Despite Enhancing Systemic Cytokine Production | American Society of NephrologyIRF4 Deficiency Abrogates Lupus Nephritis Despite Enhancing Systemic Cytokine Production | American Society of Nephrology

Three checkpoints in lupus development: Central tolerance in adaptive immunity, peripheral amplification by innate immunity and ... Constitutive ablation of dendritic cells breaks self-tolerance of CD4 T cells and results in spontaneous fatal autoimmunity. J ... 1 The pathogenesis of SLE is based on variable combinations of genetic polymorphisms that promote loss of tolerance or tissue ...
more infohttps://jasn.asnjournals.org/node/7069.full.print

Science Signaling Podcast: 26 June 2012 | Science SignalingScience Signaling Podcast: 26 June 2012 | Science Signaling

Autoreactive T cells that escape central tolerance are suppressed or eliminated by mechanisms of peripheral tolerance. ... Most autoreactive T cells are eliminated by mechanisms of central tolerance in the bone marrow or thymus before they enter the ... An inhibitory receptor blocks proliferation of autoreactive T cells to promote tolerance in the periphery. ... An inhibitory receptor blocks proliferation of autoreactive T cells to promote tolerance in the periphery. ...
more infohttp://stke.sciencemag.org/content/5/230/pc14
  • These recent advances are bringing about a paradigm shift in our views about tolerance to self-molecules with tissue-restricted expression. (nih.gov)
  • 1 The pathogenesis of SLE is based on variable combinations of genetic polymorphisms that promote loss of tolerance or tissue inflammation. (asnjournals.org)
  • 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)