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.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.Immune System: The body's defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components.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.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.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.Mice, Inbred C57BLGlucose 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).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.Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.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).Hemophilia A: The classic hemophilia resulting from a deficiency of factor VIII. It is an inherited disorder of blood coagulation characterized by a permanent tendency to hemorrhage.Mice, Inbred BALB CLymphocyte 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.Indoleamine-Pyrrole 2,3,-Dioxygenase: A dioxygenase with specificity for the oxidation of the indoleamine ring of TRYPTOPHAN. It is an extrahepatic enzyme that plays a role in metabolism as the first and rate limiting enzyme in the kynurenine pathway of TRYPTOPHAN catabolism.Forkhead Transcription Factors: A subclass of winged helix DNA-binding proteins that share homology with their founding member fork head protein, Drosophila.Autoantigens: Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.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.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.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.Immunity, Innate: The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.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.Factor VIII: Blood-coagulation factor VIII. Antihemophilic factor that is part of the factor VIII/von Willebrand factor complex. Factor VIII is produced in the liver and acts in the intrinsic pathway of blood coagulation. It serves as a cofactor in factor X activation and this action is markedly enhanced by small amounts of thrombin.Spleen: An encapsulated lymphatic organ through which venous blood filters.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.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.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).Immunity, Cellular: Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.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.Immune System Diseases: Disorders caused by abnormal or absent immunologic mechanisms, whether humoral, cell-mediated, or both.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.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.Cancer Vaccines: Vaccines or candidate vaccines designed to prevent or treat cancer. Vaccines are produced using the patient's own whole tumor cells as the source of antigens, or using tumor-specific antigens, often recombinantly produced.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.Antigens: Substances that are recognized by the immune system and induce an immune reaction.Antibody Formation: The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.Adaptive Immunity: Protection from an infectious disease agent that is mediated by B- and T- LYMPHOCYTES following exposure to specific antigen, and characterized by IMMUNOLOGIC MEMORY. It can result from either previous infection with that agent or vaccination (IMMUNITY, ACTIVE), or transfer of antibody or lymphocytes from an immune donor (IMMUNIZATION, PASSIVE).Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.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.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.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.HLA-G Antigens: Class I human histocompatibility (HLA) surface antigens encoded by alleles on locus B of the HLA complex. The HLA-G antigens are considered non-classical class I antigens due to their distinct tissue distribution which differs from HLA-A; HLA-B; and HLA-C antigens. Note that several isoforms of HLA-G antigens result from alternative splicing of messenger RNAs produced from the HLA-G*01 allele.Clonal 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.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.Chimerism: The occurrence in an individual of two or more cell populations of different chromosomal constitutions, derived from different individuals. This contrasts with MOSAICISM in which the different cell populations are derived from a single individual.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.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).Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily.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.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.Antigens, Heterophile: Antigens stimulating the formation of, or combining with heterophile antibodies. They are cross-reacting antigens found in phylogenetically unrelated species.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.Factor IX: Storage-stable blood coagulation factor acting in the intrinsic pathway. Its activated form, IXa, forms a complex with factor VIII and calcium on platelet factor 3 to activate factor X to Xa. Deficiency of factor IX results in HEMOPHILIA B (Christmas Disease).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.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.Transplantation, Heterotopic: Transplantation of tissue typical of one area to a different recipient site. The tissue may be autologous, heterologous, or homologous.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.Leukocyte Transfusion: The transfer of leukocytes from a donor to a recipient or reinfusion to the donor.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.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.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.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.Vaccines, DNA: Recombinant DNA vectors encoding antigens administered for the prevention or treatment of disease. The host cells take up the DNA, express the antigen, and present it to the immune system in a manner similar to that which would occur during natural infection. This induces humoral and cellular immune responses against the encoded antigens. The vector is called naked DNA because there is no need for complex formulations or delivery agents; the plasmid is injected in saline or other buffers.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.Immune Evasion: Methods used by pathogenic organisms to evade a host's immune system.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Hypersensitivity, Delayed: An increased reactivity to specific antigens mediated not by antibodies but by cells.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.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)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.Transplantation, Homologous: Transplantation between individuals of the same species. Usually refers to genetically disparate individuals in contradistinction to isogeneic transplantation for genetically identical individuals.Th1 Cells: Subset of helper-inducer T-lymphocytes which synthesize and secrete interleukin-2, gamma-interferon, and interleukin-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, Th1 cells are associated with vigorous delayed-type hypersensitivity reactions.Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by ANTIGEN injection or infection with microorganisms containing the antigen.Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.Immunity, Mucosal: Nonsusceptibility to the pathogenic effects of foreign microorganisms or antigenic substances as a result of antibody secretions of the mucous membranes. Mucosal epithelia in the gastrointestinal, respiratory, and reproductive tracts produce a form of IgA (IMMUNOGLOBULIN A, SECRETORY) that serves to protect these ports of entry into the body.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.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.Lymph Nodes: They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Desensitization, Immunologic: Immunosuppression by the administration of increasing doses of antigen. Though the exact mechanism is not clear, the therapy results in an increase in serum levels of allergen-specific IMMUNOGLOBULIN G, suppression of specific IgE, and an increase in suppressor T-cell activity.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.Tumor Escape: The ability of tumors to evade destruction by the IMMUNE SYSTEM. Theories concerning possible mechanisms by which this takes place involve both cellular immunity (IMMUNITY, CELLULAR) and humoral immunity (ANTIBODY FORMATION), and also costimulatory pathways related to CD28 antigens (ANTIGENS, CD28) and CD80 antigens (ANTIGENS, CD80).Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Mice, Inbred C3HGene 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.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.Pregnancy: The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.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.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Transplantation Immunology: A general term for the complex phenomena involved in allo- and xenograft rejection by a host and graft vs host reaction. Although the reactions involved in transplantation immunology are primarily thymus-dependent phenomena of cellular immunity, humoral factors also play a part in late rejection.Immunity: Nonsusceptibility to the invasive or pathogenic effects of foreign microorganisms or to the toxic effect of antigenic substances.Epitopes: Sites on an antigen that interact with specific antibodies.Heart Transplantation: The transference of a heart from one human or animal to another.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.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.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Isoantibodies: Antibodies from an individual that react with ISOANTIGENS of another individual of the same species.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Killer Cells, Natural: Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.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.Th2 Cells: Subset of helper-inducer T-lymphocytes which synthesize and secrete the interleukins IL-4, IL-5, IL-6, and IL-10. These cytokines influence B-cell development and antibody production as well as augmenting humoral responses.Coagulants: Agents that cause clotting.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.Adjuvants, Immunologic: Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.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.Salt-Tolerance: The ability of organisms to sense and adapt to high concentrations of salt in their growth environment.Antigens, Neoplasm: Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.Immunologic Factors: Biologically active substances whose activities affect or play a role in the functioning of the immune system.Glycogen Storage Disease Type II: An autosomal recessively inherited glycogen storage disease caused by GLUCAN 1,4-ALPHA-GLUCOSIDASE deficiency. Large amounts of GLYCOGEN accumulate in the LYSOSOMES of skeletal muscle (MUSCLE, SKELETAL); HEART; LIVER; SPINAL CORD; and BRAIN. Three forms have been described: infantile, childhood, and adult. The infantile form is fatal in infancy and presents with hypotonia and a hypertrophic cardiomyopathy (CARDIOMYOPATHY, HYPERTROPHIC). The childhood form usually presents in the second year of life with proximal weakness and respiratory symptoms. The adult form consists of a slowly progressive proximal myopathy. (From Muscle Nerve 1995;3:S61-9; Menkes, Textbook of Child Neurology, 5th ed, pp73-4)Genetic Vectors: DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.Lymphocyte 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.Maternal-Fetal Exchange: Exchange of substances between the maternal blood and the fetal blood at the PLACENTA via PLACENTAL CIRCULATION. The placental barrier excludes microbial or viral transmission.Mice, Inbred CBAPhotopheresis: A process in which peripheral blood is exposed in an extracorporeal flow system to photoactivated 8-methoxypsoralen (METHOXSALEN) and ultraviolet light - a procedure known as PUVA THERAPY. Photopheresis is at present a standard therapy for advanced cutaneous T-cell lymphoma; it shows promise in the treatment of autoimmune diseases.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.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.Interleukin-2: A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.Dose-Response Relationship, Immunologic: A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.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.alpha-Glucosidases: Enzymes that catalyze the exohydrolysis of 1,4-alpha-glucosidic linkages with release of alpha-glucose. Deficiency of alpha-1,4-glucosidase may cause GLYCOGEN STORAGE DISEASE TYPE II.Immune Complex Diseases: Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides SERUM SICKNESS and the ARTHUS REACTION, evidence supports a pathogenic role for immune complexes in many other IMMUNE SYSTEM DISEASES including GLOMERULONEPHRITIS, systemic lupus erythematosus (LUPUS ERYTHEMATOSUS, SYSTEMIC) and POLYARTERITIS NODOSA.Adaptation, Physiological: The non-genetic biological changes of an organism in response to challenges in its ENVIRONMENT.Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER 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)Lipopolysaccharides: Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen.H-2 Antigens: The major group of transplantation antigens in the mouse.Genetic Therapy: Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions.Toll-Like Receptors: A family of pattern recognition receptors characterized by an extracellular leucine-rich domain and a cytoplasmic domain that share homology with the INTERLEUKIN 1 RECEPTOR and the DROSOPHILA toll protein. Following pathogen recognition, toll-like receptors recruit and activate a variety of SIGNAL TRANSDUCING ADAPTOR PROTEINS.Injections, Intraperitoneal: Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall.Lymphocyte Culture Test, Mixed: Measure of histocompatibility at the HL-A locus. Peripheral blood lymphocytes from two individuals are mixed together in tissue culture for several days. Lymphocytes from incompatible individuals will stimulate each other to proliferate significantly (measured by tritiated thymidine uptake) whereas those from compatible individuals will not. In the one-way MLC test, the lymphocytes from one of the individuals are inactivated (usually by treatment with MITOMYCIN or radiation) thereby allowing only the untreated remaining population of cells to proliferate in response to foreign histocompatibility antigens.Autografts: Transplant comprised of an individual's own tissue, transferred from one part of the body to another.Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.Cell Line: Established cell cultures that have the potential to propagate indefinitely.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, 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.Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis.Blood Glucose: Glucose in blood.Recombinant Proteins: Proteins prepared by recombinant DNA technology.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.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.Antibodies, Blocking: Antibodies that inhibit the reaction between ANTIGEN and other antibodies or sensitized T-LYMPHOCYTES (e.g., antibodies of the IMMUNOGLOBULIN G class that compete with IGE antibodies for antigen, thereby blocking an allergic response). Blocking antibodies that bind tumors and prevent destruction of tumor cells by CYTOTOXIC T-LYMPHOCYTES have also been called enhancing antibodies. (Rosen et al., Dictionary of Immunology, 1989)Islets of Langerhans Transplantation: The transference of pancreatic islets within an individual, between individuals of the same species, or between individuals of different species.Mice, Inbred DBADroughts: Prolonged dry periods in natural climate cycle. They are slow-onset phenomena caused by rainfall deficit combined with other predisposing factors.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.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.Myeloid Cells: The classes of BONE MARROW-derived blood cells in the monocytic series (MONOCYTES and their precursors) and granulocytic series (GRANULOCYTES and their precursors).Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Up-Regulation: A positive 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.Administration, Oral: The giving of drugs, chemicals, or other substances by mouth.CD40 Ligand: A membrane glycoprotein and differentiation antigen expressed on the surface of T-cells that binds to CD40 ANTIGENS on B-LYMPHOCYTES and induces their proliferation. Mutation of the gene for CD40 ligand is a cause of HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 1.Rats, Inbred LewInterleukin-4: A soluble factor produced by activated T-LYMPHOCYTES that induces the expression of MHC CLASS II GENES and FC RECEPTORS on B-LYMPHOCYTES and causes their proliferation and differentiation. It also acts on T-lymphocytes, MAST CELLS, and several other hematopoietic lineage cells.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).Immunologic Memory: The altered state of immunologic responsiveness resulting from initial contact with antigen, which enables the individual to produce antibodies more rapidly and in greater quantity in response to secondary antigenic stimulus.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.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.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.Dependovirus: A genus of the family PARVOVIRIDAE, subfamily PARVOVIRINAE, which are dependent on a coinfection with helper adenoviruses or herpesviruses for their efficient replication. The type species is Adeno-associated virus 2.Allergens: Antigen-type substances that produce immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE).RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.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.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.Decidua: The hormone-responsive glandular layer of ENDOMETRIUM that sloughs off at each menstrual flow (decidua menstrualis) or at the termination of pregnancy. During pregnancy, the thickest part of the decidua forms the maternal portion of the PLACENTA, thus named decidua placentalis. The thin portion of the decidua covering the rest of the embryo is the decidua capsularis.Intestinal Mucosa: Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Interleukin-17: A proinflammatory cytokine produced primarily by T-LYMPHOCYTES or their precursors. Several subtypes of interleukin-17 have been identified, each of which is a product of a unique gene.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.Cell SeparationHomeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable.Th17 Cells: Subset of helper-effector T-lymphocytes which synthesize and secrete IL-17, IL-17F, and IL-22. These cytokines are involved in host defenses and tissue inflammation in autoimmune diseases.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.Antibodies, Antinuclear: Autoantibodies directed against various nuclear antigens including DNA, RNA, histones, acidic nuclear proteins, or complexes of these molecular elements. Antinuclear antibodies are found in systemic autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, polymyositis, and mixed connective tissue disease.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.Histocompatibility Antigens Class I: Membrane glycoproteins consisting of an alpha subunit and a BETA 2-MICROGLOBULIN beta subunit. In humans, highly polymorphic genes on CHROMOSOME 6 encode the alpha subunits of class I antigens and play an important role in determining the serological specificity of the surface antigen. Class I antigens are found on most nucleated cells and are generally detected by their reactivity with alloantisera. These antigens are recognized during GRAFT REJECTION and restrict cell-mediated lysis of virus-infected cells.HLA Antigens: Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases.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.Models, Animal: Non-human animals, selected because of specific characteristics, for use in experimental research, teaching, or testing.Hemophilia B: A deficiency of blood coagulation factor IX inherited as an X-linked disorder. (Also known as Christmas Disease, after the first patient studied in detail, not the holy day.) Historical and clinical features resemble those in classic hemophilia (HEMOPHILIA A), but patients present with fewer symptoms. Severity of bleeding is usually similar in members of a single family. Many patients are asymptomatic until the hemostatic system is stressed by surgery or trauma. Treatment is similar to that for hemophilia A. (From Cecil Textbook of Medicine, 19th ed, p1008)Cell Line, Tumor: A cell line derived from cultured tumor cells.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Tumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.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.Bone Marrow Transplantation: The transference of BONE MARROW from one human or animal to another for a variety of purposes including HEMATOPOIETIC STEM CELL TRANSPLANTATION or MESENCHYMAL STEM CELL TRANSPLANTATION.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.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.Lymphocyte Count: The number of LYMPHOCYTES per unit volume of BLOOD.Immunity, Humoral: Antibody-mediated immune response. Humoral immunity is brought about by ANTIBODY FORMATION, resulting from TH2 CELLS activating B-LYMPHOCYTES, followed by COMPLEMENT ACTIVATION.Bone Marrow Cells: Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.Intestines: The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.Phagocytosis: The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).Gene Transfer Techniques: The introduction of functional (usually cloned) GENES into cells. A variety of techniques and naturally occurring processes are used for the gene transfer such as cell hybridization, LIPOSOMES or microcell-mediated gene transfer, ELECTROPORATION, chromosome-mediated gene transfer, TRANSFECTION, and GENETIC TRANSDUCTION. Gene transfer may result in genetically transformed cells and individual organisms.Cell Communication: Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Antigens, Surface: Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.Peptides: 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.
Clusters of Pneumocystis carinii pneumonia: analysis of person-to-person transmission by genotyping. (1/6947)Genotyping at the internal transcribed spacer (ITS) regions of the nuclear rRNA operon was performed on isolates of P. carinii sp. f. hominis from three clusters of P. carinii pneumonia among eight patients with haematological malignancies and six with HIV infection. Nine different ITS sequence types of P. carinii sp. f. hominis were identified in the samples from the patients with haematological malignancies, suggesting that this cluster of cases of P. carinii pneumonia was unlikely to have resulted from nosocomial transmission. A common ITS sequence type was observed in two of the patients with haematological malignancies who shared a hospital room, and also in two of the patients with HIV infection who had prolonged close contact on the ward. In contrast, different ITS sequence types were detected in samples from an HIV-infected homosexual couple who shared the same household. These data suggest that person-to-person transmission of P. carinii sp. f. hominis may occur from infected to susceptible immunosuppressed patients with close contact within hospital environments. However direct transmission between patients did not account for the majority of cases within the clusters, suggesting that person-to-person transmission of P. carinii sp. f. hominis infection may be a relatively infrequent event and does not constitute the major route of transmission in man. (+info)
Development and function of autospecific dual TCR+ T lymphocytes. (2/6947)Recent studies have challenged the long held concept that each T lymphocyte expresses on its surface only a single, unique alphabetaTCR. Dual TCR+ T cells have been recognized, however, their origin and potential to escape screening for self-reactivity remain obscure. We now report the thymic generation of dual alphabetaTCR+ T cells in the H-2Db/H-Y-specific TCR transgenic (Tg) mouse. Dual TCR+ thymocytes were positively selected less efficiently than single TCR+ thymocytes, although a subset attained maturity. Importantly, when TCR Tg mice were bred onto a negatively selecting background, auto-specific cells survived central deletion and matured as CD4+ dual TCR+ cells. These cells were autoreactive when CD8 expression was restored. The existence of autospecific, dual TCR+ T cells may have implications for the maintenance of self tolerance. (+info)
Immunosurveillance of alglucerase enzyme therapy for Gaucher patients: induction of humoral tolerance in seroconverted patients after repeat administration. (3/6947)Alglucerase, a macrophage-targeted enzyme replacement therapy for Gaucher disease, has been successfully used for several years to improve clinical symptoms and reverse disease progression. As part of an immunosurveillance program, 1,122 Gaucher patients were monitored for antibody response to glucocerebrosidase, the active component of alglucerase. Seroconversion was detected in 142 patients (12.8%) by enzyme-linked immunosorbent assay (ELISA) and confirmed by radioimmunoprecipitation. The majority (75%) of the seroconverted population had no detectable levels of circulating inhibitory antibody as assessed by in vitro inhibition of enzymatic activity of the therapeutic molecule. Of the remaining patients with putative inhibitory antibodies, the majority had only low levels of serum inhibitory activity, which was transient. A very small number of patients were identified as developing true neutralizing antibodies, as defined by the development of antibodies that impacted clinical efficacy. Many of the patient antibody responses were also diminished with time. Eighty-two of the 142 seroconverted patients have stopped producing antibody to the molecule and appear tolerized. The mean time for humoral tolerization was 28 months from initiation of therapy. Of 64 seroconverted patients followed for at least 30 months of therapy, the tolerization rate was 93%. These results show that although 12.8% of the patients on therapy developed antibodies to the molecule, 90% of these patients became tolerized over time. (+info)
Tolerance to antigen-presenting cell-depleted islet allografts is CD4 T cell dependent. (4/6947)Pretreatment of pancreatic islets in 95% oxygen culture depletes graft-associated APCs and leads to indefinite allograft acceptance in immunocompetent recipients. As such, the APC-depleted allograft represents a model of peripheral alloantigen presentation in the absence of donor-derived costimulation. Over time, a state of donor-specific tolerance develops in which recipients are resistant to donor APC-induced graft rejection. Thus, persistence of the graft is sufficient to induce tolerance independent of other immune interventions. Donor-specific tolerance could be adoptively transferred to immune-deficient SCID recipient mice transplanted with fresh immunogenic islet allografts, indicating that the original recipient was not simply "ignorant" of donor antigens. Interestingly, despite the fact that the original islet allograft presented only MHC class I alloantigens, CD8+ T cells obtained from tolerant animals readily collaborated with naive CD4+ T cells to reject donor-type islet grafts. Conversely, tolerant CD4+ T cells failed to collaborate effectively with naive CD8+ T cells for the rejection of donor-type grafts. In conclusion, the MHC class I+, II- islet allograft paradoxically leads to a change in the donor-reactive CD4 T cell subset and not in the CD8 subset. We hypothesize that the tolerant state is not due to direct class I alloantigen presentation to CD8 T cells but, rather, occurs via the indirect pathway of donor Ag presentation to CD4 T cells in the context of host MHC class II molecules. (+info)
IL-4 and IL-10 are both required for the induction of oral tolerance. (5/6947)Protection from the development of experimental autoimmune uveitis (EAU) can be induced by feeding mice interphotoreceptor retinoid binding protein before uveitogenic challenge with the same protein. Two different regimens are equally effective in inducing protective tolerance, although they seem to do so through different mechanisms: one involving regulatory cytokines (IL-4, IL-10, and TGF-beta), and the other with minimal involvement of cytokines. Here we studied the importance of IL-4 and IL-10 for the development of oral tolerance using mice genetically engineered to lack either one or both of these cytokines. In these animals we were able to protect against EAU only through the regimen inducing cytokine-independent tolerance. When these animals were fed a regimen that in the wild-type animal is thought to predominantly induce regulatory cells and is associated with cytokine secretion, they were not protected from EAU. Interestingly, both regimens were associated with reduced IL-2 production and proliferation in response to interphotoreceptor retinoid binding protein. These findings indicate that both IL-4 and IL-10 are required for induction of protective oral tolerance dependent on regulatory cytokines, and that one cytokine cannot substitute for the other in this process. These data also underscore the fact that oral tolerance, manifested as suppression of proliferation and IL-2 production, is not synonymous with protection from disease. (+info)
Altered helper T lymphocyte function associated with chronic hepatitis B virus infection and its role in response to therapeutic vaccination in humans. (6/6947)Theradigm-hepatitis B virus (HBV) is an experimental lipopeptide vaccine designed to stimulate induction of HBV-specific CTL responses in HLA-A2 individuals. Previous studies had demonstrated high immunogenicity in healthy volunteers, but comparatively weak CTL responses in chronically infected HBV patients. Herein, we examined helper T lymphocyte (HTL) responses in chronically infected patients. Despite normal proliferation and IL-2 secretion, IL-12 and IFN-gamma secretion in vitro in response to the vaccine was reduced compared with healthy volunteers. A similar pattern of cytokine secretion was observed following mitogen stimulation, suggesting a general altered balance of Th1/Th2 responses. Further analysis indicated that HTL recall responses to whole tetanus toxoid protein were reduced in chronically infected subjects, and reduced responsiveness correlated with the outcome of Theradigm-HBV immunization. Finally, experiments in HBV transgenic mice indicated that the nonnatural Pan DR HTL epitope, PADRE, is capable of inducing high levels of IFN-gamma secretion and that its inclusion in a lipopeptide incorporating an immunodominant Ld-restricted CTL epitope resulted in breaking tolerance at the CTL level. Overall, our results demonstrate an alteration in the quality of HTL responses induced in chronically infected HBV patients and suggest that use of a potent HTL epitope may be important to overcome CTL tolerance against specific HBV Ags. (+info)
Activation in vivo of retroperitoneal fibromatosis-associated herpesvirus, a simian homologue of human herpesvirus-8. (7/6947)Retroperitoneal fibromatosis-associated herpesvirus of rhesus macaques (RFHVMm) is a gammaherpesvirus closely related to human herpesvirus-8 (HHV-8), which is thought to be a necessary cofactor for the development of Kaposi's sarcoma (KS) in humans. Here, RFHVMm infection of rhesus macaques exposed to the D-type retrovirus simian retrovirus-2 (SRV-2) is described. Development of SRV-2 viraemia, infection with simian immunodeficiency virus or administration of cyclosporin A could result in persistent RFHVMm viraemia. From this, it is concluded that productive retrovirus infection or otherwise-induced immune suppression has the ability to activate this herpesvirus in vivo. Elevated levels of circulating interleukin-6, a cytokine that plays a central role in KS, were found in RFHVMm-viraemic animals. In viraemic animals, RFHVMm was found in tissues that are common sites for the development of AIDS-associated KS, especially the oral cavity. Together, these data suggest a common biology between RFHVMm infection of macaques and HHV-8 infection and pathogenesis in humans. (+info)
B7-2 expressed on EL4 lymphoma suppresses antitumor immunity by an interleukin 4-dependent mechanism. (8/6947)For T cells to become functionally activated they require at least two signals. The B7 costimulatory molecules B7-1 and B7-2 provide the "second signal" pivotal for T cell activation. In this report, we studied the relative roles of B7-1 and B7-2 molecules in the induction of antitumor immunity to the T cell thymoma, EL4. We generated EL4 tumor cells that expressed B7-1, B7-2, and B7-1+B7-2 by transfecting murine cDNAs. Our results demonstrate that EL4-B7-1 cells are completely rejected in syngeneic mice. Unlike EL4-B7-1 cells, we find that EL4-B7-2 cells are not rejected but progressively grow in the mice. A B7-1- and B7-2-EL4 double transfectant was generated by introducing B7-2 cDNA into the EL4-B7-1 tumor line that regressed in vivo. The EL4-B7-1+B7-2 double transfectant was not rejected when implanted into syngeneic mice but progressively grew to produce tumors. The double transfectant EL4 cells could costimulate T cell proliferation that could be blocked by anti-B7-1 antibodies, anti-B7-2 antibodies, or hCTLA4 immunoglobulin, showing that the B7-1 and B7-2 molecules expressed on the EL4 cells were functional. In vivo, treatment of mice implanted with double-transfected EL4 cells with anti-B7-2 monoclonal antibody resulted in tumor rejection. Furthermore, the EL4-B7-2 and EL4-B7-1+B7-2 cells, but not the wild-type EL4 cells, were rejected in interleukin 4 (IL-4) knockout mice. Our data suggests that B7-2 expressed on some T cell tumors inhibits development of antitumor immunity, and IL-4 appears to play a critical role in abrogation of the antitumor immune response. (+info)
Frontline Science: Endotoxin-induced immunotolerance is associated with loss of monocyte metabolic plasticity and reduction of...
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 responses to ex vivo stimulation. Next, the effects of altered cellular metabolism on monocyte functions were validated in vitro. Ex vivo ...
Immune tolerance - Wikipedia
Immune tolerance, or immunological tolerance, or immunotolerance, is a state of unresponsiveness of the immune system to substances or tissue that have the capacity to elicit an immune response in given organism. It contrasts with conventional immune-mediated elimination of foreign antigens (see Immune response). Tolerance is classified into central tolerance or peripheral tolerance depending on where the state is originally induced-in the thymus and bone marrow (central) or in other tissues and lymph nodes (peripheral). The mechanisms by which these forms of tolerance are established are distinct, but the resulting effect is similar. Immune tolerance is important for normal physiology. Central tolerance is the main way the immune system learns to discriminate self from non-self. Peripheral tolerance is key to preventing over-reactivity of the immune system to various environmental entities (allergens, gut microbes, etc.). Deficits in central or peripheral tolerance also cause autoimmune ...
Afweerysteem Algemeen miR142 Effect Lord 2019 - 1500
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 regulator of intracellular cAMP, controlling Treg suppressive function. Mir142 was associated with a super enhancer bound by the Treg lineage-determining transcription factor ...
Short course immune induction therapy - Wikipedia
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 tolerance can be defined as the ability of the immune system to distinguish between self and non-self, or harmless and harmful. T-cells are able to distinguish between self and ...
Correlation of tolerogenicity of a viral antigen with its immunogenicity. - The Jenner Institute
Induction of B cell tolerance or activation was analyzed with vesicular stomatitis virus (VSV) glycoprotein (G) expressed as a neo-self Ag. A membrane form of VSV-G expressed in all tissues, including the bone marrow, induced unresponsiveness at both the Th and B cell level, whereas a soluble form of VSV-G expressed peripherally in liver and kidney did not tolerize B cells and only reversibly anergized Th cells. Interestingly, a similar correlation was found for activation of mature lymphocytes. When mature normal spleen cells were transferred into the two transgenic mouse lines, the membrane form of VSV-G was strongly immunogenic for both Th and B cells, and high VSV-G-specific IgG Ab titers were induced in these transgenic mice. In contrast, spleen cells transferred into mice expressing the soluble form of VSV-G were not activated, and no VSV-G specific Abs were induced. These results indicate that highly immunogenic Ags are strongly tolerogenic for both immature B and T cells.
Neonatal Tolerance Revisited: Turning on Newborn T Cells with Dendritic Cells | Zenodo
For some time it has been thought that antigenic challenge in neonatal life is a tolerogenic rather than immunogenic event. Reexamination of the classic neonatal tolerance experiments of Billingham, Brent, and Medawar showed that tolerance is not an intrinsic property of the newborn immune system, but that the nature of the antigen-presenting cell determines whether the outcome is neonatal tolerance or immunization.
Oral tolerance induction is defective during the neonatal period in the mouse (39.42) | The Journal of Immunology
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 than donor T cells in adults. These ...
Current RFPs | Immune Tolerance Network
The Immune Tolerance Network seeks to provide funding and strategic support for clinical trials designed to induce immune tolerance in allergy and asthma, autoimmune disease, transplantation, and type 1 diabetes. The ITN is currently seeking proposals for clinical trials of immune tolerance in transplantation using deceased-donor organs.
"Immunologic unresponsiveness of mouse spleen sensitized to allogeneic " by B F. Argyris and F D. Lustro
THU0270 Activation of Plasmacytoid Dendritic Cells by Apoptotic Particles - Mechanism for The Loss of Immunologic Tolerance in...
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. ...
Tolerance induced by inhaled antigen involves CD4<sup>+</sup> T cells expressing membrane-bound TGF-β and...
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 naive recipient mice. While cells expressing cell surface TGF-β were detectable in mice with inflammation, albeit at a lower frequency compared with that in tolerized mice, only those from ...
Differences in calcium requirements for B-cell tolerance and immunity. - Oxford Neuroscience
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.
Glutamate (EAAT) Transporters
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. ...
Wissenschaftliche Publikationen des Instituts | Max-Planck-Institut für Kolloid- und Grenzflächenforschung
Details of N01AI15416-26-0-4: Immune tolerance network: type 1 diabetes
The Immune Tolerance Network is dedicated to the clinical evaluation of novel tolerance-inducing therapies that will ¿re-educate¿ the immune system to eliminate injurious immune responses. The ITN is conducting clinical trials in autoimmune diseases such as Type 1 Diabetes. In addition, to understand the underlying mechanisms of action of the candidate therapies and to monitor tolerance, the ITN has established state of the art core laboratory facilities to conduct integrated mechanistic studi...
The lollipop plot above illustrates recurrent (observed in 3 or more out of 4440 TCGA tumor samples from 15 cancer types) and therefore potentially oncogenic missense mutations (click on Show Cancer Mutations). The bar plot below shows the proportion of tumor samples that have any kind of altering mutation(s) in the given protein. ...
Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor-initiated cell death, is involved in tumor suppression as well as survival of several cancers, is required for oxygen radical production by NADPH oxidase and acts as positive or negative regulator in platelet functional responses. Negatively regulates B cell proliferation and also has an important function in self-antigen induced B cell tolerance induction. Upon DNA damage, activates the promoter of the death-promoting transcription factor BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis. In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53. In the case of ER stress or DNA damage-induced ...
Searching For The Secrets Of Drug-Free Transplants: University Of Pittsburgh, Through Immune Tolerance Network, To Develop...
4th Antigen Specific Immune Tolerance Digital Summit
Immune suppressive mechanisms in HCV infection. HCV mut | Open-i
Uncovering the role of the placenta in pregnancy immune tolerance - AgBioResearch
Astellas sets up immune tolerance JV in $760m deal - PharmaTimes
CD1D | Cancer Genetics Web
Immune responses and their modulation within the liver are critical to the outcome of liver malignancies. In late-stage tumors, secreted TGF-β promotes oncogenic functions and can confer tolerogenicity to some immune cells like DCs. The TGF-β signaling pathway is involved in the control of several biological processes, including immunosurveillance. The aim of the present study was to assess CD1a(+) and CD83(+) DCs and to evaluate the impact of TGF-β pathway on DCs maturation and distribution in the liver metastases from gastric and colorectal tumors. The percentage of CD83(+) DCs in the liver tissue, surrounding metastasis and in the metastasis-free liver was measured by flow cytometry, and TGF-β levels were assessed in the tissue supernatant from the peritumoral liver after mononuclear cell isolation and in the sera of the same patients. CD1a(+) and CD83(+) DCs were observed in the tumor stroma and border. Out of 73 patients, there was cytoplasmic reactivity: of TGF-β1 in 37 (50.7%); of ...
peripheral tolerance induction to self antigen QuickView - Correlation Engine
JCI - An integrated view of suppressor T cell subsets in immunoregulation
Furthermore, it has also been shown that a distinct population of antigen-specific, non-Qa-1-restricted CD8+CD28- cells can suppress immune responses by directly interacting with antigen-presenting DCs and rendering these cells tolerogenic (64-66). The suppression involves the upregulation of inhibitory Ig-like transcript 3 (ILT3) and ILT4 receptors expressed on the DCs. APCs tolerized by CD8+ T cells show reduced expression of costimulatory molecules and induce antigen-specific unresponsiveness in CD4+ T helper cells. The precise function of these cells in vivo is not clear, and it is not known whether they interact with the Qa-1-restricted CD8+ suppressor cells or, alternatively, whether Qa-1-restricted T cells induce tolerogenic DCs.. Finally, the Qa-1-dependent regulatory CD8 pathway has begun to be translated from mice to humans with the in vitro findings that human CD8+ T cells can be induced to differentiate into regulatory cells whose function is dependent on HLA-E, the human homolog of ...
Peripheral CD8+ T Cell Tolerance - Linda Sherman
Speakers | Antigen Specific Immune Tolerance | Feb 25-27 | Boston
The roles of Synoviolin in immune tolerance and autoimmunity - Deyu Fang
The immune system exists to protect the host against pathogenic organisms and highly complex pathways of recognition, response, elimination and memory have evolved in order to fulfil this role. The immune system also acts to ensure tolerance to self, to food and other environmental components, and to commensal bacteria. A breakdown in the tolerogenic pathways can also lead to inflammatory diseases. The prevalence of inflammatory diseases, including atopic disorders, has increased over the last 60 years. The development of tolerance is the result of active immune mechanisms and both development and maintenance of tolerance are lifelong processes which start very early in life, even prenatally. Profound immunologic changes occur during pregnancy, involving a polarization of T helper (Th) cells towards a dominance of Th2 and regulatory T cell effector responses in both mother and fetus. This situation is important to maintain pregnancy through avoidance of the rejection of the immunologically ...
Who We Are | RESTARRT
JCI - microRNA-142-mediated repression of phosphodiesterase 3B critically regulates peripheral immune tolerance
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. Pharmacological inhibition and genetic ablation of PDE3B prevented autoimmune disease and reversed the ...
Can Botulism Cause a Coma? Otto Warmbier Is In An Unresponsive State
Sustained suppression by Foxp3+ regulatory T cells is vital for infectious transplantation tolerance. - Nuffield Department of...
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 Foxp3(+) cells sustain tolerance by converting naive T cells into the next generation of Foxp3(+) cells. Empowering Foxp3(+) regulatory T cells in vivo offers a tractable
Collaborative Network for Clinical Research on Immune Tolerance - Offcampus Portion | Global Research Projects
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:. ...
Ex-vivo expanded DC induce donor-specific central and peripheral tolerance and prolong the acceptance of donor skin allografts
Dendritic cells (DCs) are known to regulate immune responses by inducing both central and peripheral tolerance. DCs play a vital role in negative selection of developing thymocytes by deleting T cells with high-affinity for self-peptide-major histocompatibility complexes. In the periphery, DCs mediate peripheral tolerance by promoting regulatory T-cell development, induction of T-cell unresponsiveness, and deletion of activated T cells. We studied whether allogeneic DCs, obtained from bone marrow cultured with either Flt3L (FLDCs) or granulocyte-macrophage colony-stimulating factor (GMDCs), could induce allospecific central and peripheral tolerance after IV injection; B cells were used as a control. The results showed that only FLDCs reached the thymus after injection and that these cells induced both central and peripheral tolerance to donor major histocompatibility complexes. For central tolerance, injection of FLDCs induced antigen-specific clonal deletion of both CD8 and CD4 single-positive
Neuroantigen-specific, tolerogenic vaccines: GM-CSF is a fusion partner that facilitates tolerance rather than immunity to...
Background Vaccination strategies that elicit antigen-specific tolerance are needed as therapies for autoimmune disease. This study focused on whether cytokine-neuroantigen (NAg) fusion proteins could inhibit disease in chronic murine models of experimental autoimmune encephalomyelitis (EAE) and thus serve as potential therapeutic modalities for multiple sclerosis. Results A fusion protein comprised of murine GM-CSF as the N-terminal domain and the encephalitogenic MOG35-55 peptide as the C-terminal domain was tested as a tolerogenic, therapeutic vaccine (TTV) in the C57BL/6 model of EAE. Administration of GMCSF-MOG before active induction of EAE, or alternatively, at the onset of EAE blocked the development and progression of EAE. Covalent linkage of the GM-CSF and MOG35-55 domains was required for tolerogenic activity. Likewise, a TTV comprised of GM-CSF and PLP139-151 was a tolerogen in the SJL model of EAE. Conclusion These data indicated that fusion proteins containing GM-CSF coupled to ...
Intranasal Immunization With an Apolipoprotein B-100 Fusion Protein Induces Antigen-Specific Regulatory T Cells and Reduces...
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 induction of anterior chamber associated immune deviation with Type II collagen (P1045) | The Journal of Immunology
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 efferent Tregs in the spleen. CII-mediated ACAID induction ...
Delivery of alloantigens via apoptotic cells generates dendritic cells with an immature tolerogenic phenotype
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 histocompatibility complex antigens of class II, CD86, and CD80 molecules and the secretion of a tolerogenic cytokine pattern. Furthermore, we showed that VD3DCs ...
Mechanism of immune tolerance induction in antigen-specific human autoimmune disease.
Multiple sclerosis (MS) is an inflammatory disease that affects the central nervous system and is considered to be a T-cell mediated autoimmune disease. The "ideal" method in treating MS would be an antigen-specific therapy that does not require generalized immunosuppression. To date there are no definitive treatments for MS but there are several licensed therapies such as -interferon. Unfortunately the effect of interferon (IFN) is reduced by the development of neutralizing antibodies (NAbs) in up to 35% of MS patients within two years of starting treatment. An immunization schedule was developed in the BALB/c mice by subcutaneous administration of recombinant human IFN, and this resulted in development of high incidence of NAbs to the protein in the BALB/c model termed "NAbs model". The mechanism of NAbs formation in this model is believed to be similar to that observed in IFN-treated MS patients with NAbs, which is as a result of an immune response to the protein. We elected ...
Essential requirement for major histocompatibility complex recognition in T-cell tolerance induction. - The Kennedy Institute...
The induction of T-cell responses involves the recognition of extrinsic antigen in association with antigens of the major histocompatibility complex (MHC), in mice and man, with different T cells recognizing antigen in association with either class I (H-2K/D, HLA-A, B, C) or class II (Ia, HLA-D/DR) MHC antigens. However, the requirement of MHC recognition in the induction of immunological tolerance remains ill defined. With human T helper clones recognizing synthetic peptides of influenza haemagglutinin (HA-1), we have investigated the nature of antigen-induced stimulation, and antigen-induced antigen-specific unresponsiveness, immunological tolerance. Tolerance is not due to cell death, as the cells remain responsive to interleukin-2 and is associated with the loss of T3 antigen from the cell surface. Using monoclonal antibodies to the non-polymorphic regions of human class II antigens to inhibit the induction of T-cell tolerance we report here that induction of tolerance requires the recognition of
Liver-expressed Igκ superantigen induces tolerance of polyclonal B cells by clonal deletion not κ to λ receptor editing
Little is know about the nature of peripheral B cell tolerance or how it may vary in distinct lineages. Although autoantibody transgenic studies indicate that anergy and apoptosis are involved, some studies claim that receptor editing occurs. To model peripheral B cell tolerance in a normal, polyclonal immune system, we generated transgenic mice expressing an Igκ-light chain-reactive superantigen targeted to the plasma membrane of hepatocytes (pAlb mice). In contrast to mice expressing κ superantigen ubiquitously, in which κ cells edit efficiently to λ, in pAlb mice, κ B cells underwent clonal deletion. Their κ cells failed to populate lymph nodes, and the remaining splenic κ cells were anergic, arrested at a semi-mature stage without undergoing receptor editing. In the liver, κ cells recognized superantigen, down-regulated surface Ig, and expressed active caspase 3, suggesting ongoing apoptosis at the site of B cell receptor ligand expression. Some, apparently mature, κ B1 and ...
Frontiers | Transplantation Tolerance Induction: Cell Therapies and Their Mechanisms | Immunology
Cell based therapies have been studied extensively in the context of transplantation tolerance induction. The most successful protocols have relied on transfusion of bone marrow prior to the transplantation of a renal allograft. However, it is not clear that stem cells found in bone marrow are required in order to render a transplant candidate immunologically tolerant. Accordingly, mesenchymal stem cells, regulatory myeloid cells, T regulatory cells, and other cell types, are being tested as possible routes to tolerance induction, in the absence of donor derived stem cells. Early data with each of these cell types have been encouraging. However, the induction regimen capable of achieving consistent tolerance, whilst avoiding unwanted sided effects, and which is scalable to the human patient, has yet to be identified. Here we present the status of investigations of various tolerogenic cell types and the mechanistic rationale for their use in in tolerance induction protocols.
Interleukin-15 is not required for the induction or maintenance of orally induced peripheral tolerance - Strathprints
Orally induced tolerance is a physiologically relevant form of peripheral tolerance, which is believed to be important for the prevention of pathological immune responses in the gut. Of several mechanisms proposed to mediate oral tolerance, one that has received much attention recently is the concept of regulatory CD4+ T cells. As recent studies have suggested that interleukin (IL)-15 may be important for the differentiation and maintenance of regulatory CD4+ T cells, we have examined the role of IL-15 in oral tolerance, using a soluble form of the IL-15 receptor (sIL-15R) which blocks the biological effects of IL-15 in vivo. Oral tolerance induced by feeding mice ovalbumin (OVA) in a low-dose regimen believed to induce regulatory T cell activity was not affected by the administration of sIL-15R during either the induction or maintenance phase of tolerance. Thus, oral tolerance does not involve an IL-15-dependent mechanism.. ...
The Use of Oral Tolerance in the Therapy of Chronic Inflamma... : Journal of Pediatric Gastroenterology and Nutrition
Although oral tolerance was first described in 1911 (1), it was not until the later 1970s that investigators started to address the mechanisms involved (2-4). An expansion of interest has evolved in the past 20 years as various laboratories have attempted to use this form of induced immunosuppression to counteract various chronic inflammatory/autoimmune diseases. A clearer understanding of the parameters regulating oral tolerance has emerged. First and foremost is the observation that multiple forms of tolerance exist. Initial studies by Challacombe et al. (2), Mowat et al. (3), and Waksman et al (4) all documented that regulatory CD8+ T cells existed in the spleen following oral antigen administration and that these cells, but not CD4+ T cells, could transfer the tolerant state to a naive animal. The mechanism whereby these CD8+ T cells were activated was not elucidated. Richman et al. (5) and Santos et al. (6) subsequently demonstrated that tolerance could also be transferred with Peyers ...
KAKEN - Research Projects | Oral Tolerance Induction by Type V Collagen in Lung Transplantation (KAKENHI-PROJECT-15591466)
Receptor editing and genetic variability in human autoreactive B cells | JEM
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 tolerance checkpoints, but they have been limited to a poorly defined set of self-Ags without a clear understanding of how these Ags directly affect B cells in vivo. In fact, although a significant reduction in the frequency of autoreactive clones in the human B ...
TGF-beta-induced myelin peptide-specific regulatory T cells mediate antigen-specific suppression of induction of experimental...
Cytokines and peripheral tolerance to alloantigen. - Physiology, Anatomy and Genetics
The induction of peripheral tolerance to alloantigen is accompanied in many cases by a decrease in the production of cytokines such as IL-2 and IFN gamma, yet a sustained production of cytokines such as IL-10 and IL-4. Whether or not this altered pattern of cytokine production in tolerant animals is causally related to the induction and/or maintenance of the tolerant state has yet to be fully determined, although experiments blocking selectively the action of IL-2 with CD25 antibodies suggest that manipulation of cytokine production may at least be a route to tolerance. Alternative methods for directly influencing the cytokine balance are sought and recent experiments on the CD28/CTLA-4-B7 interaction suggest a possible approach.
Real-time immune cell interactions in target tissue during autoimmune-induced damage and graft tolerance | JEM
Control of immune damage at the effector phase is a crucial and perhaps the most realistic therapeutic target in clinical intervention of immune-mediated diseases (Chatenoud, 2011). Improvement of therapeutic interventions will require in-depth understanding of the immune cell behavior in target tissues and of the reaction of target tissue cells in response to insult. The current study suggests that the contact-dependent mode of immune cell interaction in the target tissue is a critical part of pathophysiology at the effector phase of immune responses, and immune tolerance induction may be facilitated by promoting intimacy between pathogenic and protective immune cells. In this regard, it is highly relevant that tissue antigen-specificity, as opposed to bystander killing (Tite and Janeway, 1984), shapes tissue fate in the effector phase.. With the tools currently available for longitudinal imaging of antigen-specific T cells in target tissues, we uncovered some basic behaviors of different ...
Probe ordered into non-responsiveness of dial 100 helpline | Delhi News - Times of India
Comparative study of clinical grade human tolerogenic dendritic cells - pdf descargar
Comparative study of clinical grade human tolerogenic dendritic cells. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Specific Immunosuppressive Mechanisms that Have Been Identified in Recent Years | Immunopaedia
David H Sachs, MD | CUMC
Dr. Sachs major areas of research are the following:. A. Induction of transplantation tolerance:. A major thrust of transplantation research in this laboratory has been directed toward induction of tolerance as a means of permitting transplantation of organs to be achieved without a requirement for immunosuppressive drugs. Two major models for tolerance induction are studied:. 1) Regulatory tolerance: Using miniature swine with defined MHC haplotypes (see below), Dr. Sachs and colleagues demonstrated that a short course of immunosuppression with a high-dose of calcineurin inhibitors is capable of inducing long-term tolerance in juvenile animals. This phenomenon has become and remains an important basic model for the study of tolerance induction across MHC barriers in a large animal model. Among active studies being carried out in this model are: a) the role of the thymus in permitting regulatory tolerance to develop; b) the dependence of tolerance on T regulatory cells; c) the adoptive transfer ...
Seminario INCLIVA - Fernando Macian | INCLIVA
El seminario titulado Mecanismos moleculares que regulan la tolerancia en los linfocitos T. Relevancia para el desarrollo de inmunoterapia será impartido por el Dr. Fernando Macian el próximo lunes 7 de septiembre de 2015 a partir de las 13.00 h. en el Salón de Actos del edificio del Instituto de Investigación Sanitaria INCLIVA. Macian Lab (overview): The antigen receptors of T cells recognize not only antigens derived from pathogenic cells and organisms, but also self-antigens expressed on the bodys own tissues. In healthy individuals, self-antigens do not elicit a significant immune response. Self-reactive lymphocytes are clonally eliminated during development and cells that survive this process are rendered tolerant in the periphery. Two of the major of the mechanisms responsible for peripheral T cell tolerance are anergy, an intracellular process in which antigen receptors become uncoupled from their downstream signaling pathways, and regulatory T cells, a population of T cells with the
Translating tolerogenic therapies to the clinic - where do we stand and what are the barriers? | Frontiers Research Topic
This Research Topic is a call for papers to provide an up to date assessment of current attempts to introduce tolerogenic therapies into clinical practice. Tolerance has been a highly sought after goal in the field of organ transplantation for over half a century, and is now readily achievable in rodent models, but considerable barriers remain to successfully translating tolerogenic treatments to the clinic. The initial call for this Research Topic has been aimed to provide an overview of recent advances made within the European RISET and American ITN networks with regard to tolerogenic strategies in clinical transplantation, autoimmune disease, and allergy. Articles will also cover the barriers to clinical tolerance induction and new emerging approaches to overcome such barriers. 1. Collaborative networks working towards the goal of therapeutic tolerance induction 2. Prope tolerance and minimization of immunosuppression 3. Lessons from operationally tolerant patients 4.
CD3+ T cells in severe combined immunodeficiency (scid) mice. II. Transplantation of dm2 lymphoid cells into semi-allogeneic...
AB0022 Accumulation of circulating autoreactive naïve b cells reveal defects of early b cell tolerance checkpoints in patients...
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.. ...
MALT1 protease: equilibrating immunity versus tolerance | The EMBO Journal
The reported duality of the MALT1 protease to promote cell intrinsic T‐cell effector functions and to suppress activated T cells in a Treg‐dependent manner raises a number of interesting questions. Even though the adoptive transfer demonstrates the potential of Tregs to counteract the autoimmunity, it remains open, if the reduced number of Tregs is indeed sufficient to cause the inflammatory phenotype. In the adoptive transfer experiment, only very few Tregs are sufficient to rescue the autoimmune phenotype raising the possibility that MALT1C472A/C472A Tregs may be less functional. In addition, the increase in IFN‐γ and IL‐4 production in MALT1 protease mutant mice may also indicate that deregulated T‐cell effector functions could also be involved in the early onset of gastritis, which is no longer counteracted due to the loss of peripheral T‐cell tolerance. In this respect, it remains an unresolved question why the autoimmune phenotype is manifested as gastritis. One can speculate ...
Modulation of antigen-specific T-cells as immune therapy for chronic infectious diseases and cancer.
T-cell responses are induced by antigen presenting cells (APC) and signals from the microenvironment. Antigen persistence and inflammatory microenvironments in chronic infections and cancer can induce a tolerant state in T-cells resulting in hyporesponsiveness, loss of effector function, and weak biochemical signaling patterns in response to antigen stimulation. Although the mechanisms of T-cell tolerance induced in chronic infection and cancer may differ from those involved in tolerance to self-antigen, the impaired proliferation and production of IL-2 in response to antigen stimulation are hallmarks of all tolerant T cells. In this review, we will summarize the evidence that the immune responses change from non-self to "self"-like in chronic infection and cancer, and will provide an overview of strategies for re-balancing the immune response of antigen-specific T cells in chronic infection and cancer without affecting the homeostasis of the immune system ...
Surprise disrupts cognition via a fronto-basal ganglia suppressive mechanism
Surprising events markedly affect behaviour and cognition, yet the underlying mechanism is unclear. Surprise recruits a brain mechanism that globally suppresses motor activity, ostensibly via the subthalamic nucleus (STN) of the basal ganglia. Here, we tested whether this suppressive mechanism exten …
Currently Enrolling Trials in Liver Transplantation | Immune Tolerance Network
Tolerance and immune suppression in the tumor microenvironment
The concept of immunological tolerance has guided and permeated much of modern immunology. Ray Owens ground-breaking observations in twin cattle provided the first mechanistic explanation for tolerance to self-molecules and established tolerance as a beneficial process that protects the host agains …
Myoungsun Son, PhD | The Feinstein Institute for Medical Research
The main interest of Dr. Son is to address relevant questions and make significant contributions to the understanding of lupus and autoimmune disease, as well as to the development of effective therapies. In addition, she would like to bring her expertise and enthusiasm to guide young scientists.. Dr. Son pursued her PhD at Ewha Womans University in Seoul, Korea where she carried out studies of T-cell homeostasis as well as peripheral T cell tolerance. Dr. Son identified a novel gene, LIME, and characterized its function in T cells in vitro and in vivo in the lab of Dr. Yungdae Yun of the Division of Life Science.. After receiving her PhD degree, Dr. Son remained in the Dr. Yuns lab to continue her research as a Post-doctoral research fellow. After two years, she was promoted to Research Professor. During that time, Dr. Son focused on designing a peptide fragment of LIME capable of inducing activation induced cell death in an animal model of autoimmune disease. She had the opportunity to mentor ...
Health Effects of Vitamins: The role of Vitamin A in tolerance and immunity??
According to the study of "The role of retinoic acid in tolerance and immunity" by Hall JA, Grainger JR, Spencer SP, Belkaid Y., posted in US National Library of Medicine National Institutes of Health, researchers indicated that we will prvide a crucial contributions of RA to both immunological tolerance and the elicitation of adaptive immune responses and acomprehensive overview of the cell types and factors that control the production of RA and discuss how host perturbations may affect the ability of this metabolite to control tolerance and immunity or to instigate pathology ...
Generating Immune Tolerance for the Embryo/Fetus - Hold the Sugar, Pass the Fat
Immunologic Tolerance as Taught by Allografts | SpringerLink
Ignorance, the Surprising Key to Your Success
Piglit] [PATCH 2/9] arb direct state access: Added glTransformFeedbackBufferBase tests
On Fri, Feb 27, 2015 at 1:04 PM, Laura Ekstrand ,laura at jlekstrand.net, wrote: , You only need to compute tolerance once, but you need to call equal() , lots of times. You should make a static variable tolerance at the top of , the file and call piglit_compute_probe_tolerance in piglit_init to , initialize it. Otherwise, this seems inefficient. FWIW theres also an extern float piglit_tolerance. All that function does is a helper for dealing with various funky formats (like luminance/alpha). I think you can just use piglit_tolerance directly ...
How not to promote bad practice - Drafting Standards, GD&T & Tolerance Analysis - Eng-Tips
self tolerance - oi
Lack of Immune Supression Capability
Category - Immune Support - NaturalWellBeing.com
Word of the day! Fresh! Fresh! Fresh!: Tolerance
Maternal physiological changes in pregnancy
Immune toleranceEdit. Main article: Immune tolerance in pregnancy. The fetus inside a pregnant woman may be viewed as an ... Insulin tolerance test. Response increases during first half of pregnancy and then normalizes until several weeks postpartum ... Glucose tolerance test. Peak glucose increases, and glucose concentration remains elevated for longer ...
CS1 maint: Multiple names: authors list (link) Steinman, Ralph M. (2004). "Dendritic Cells and Immune Tolerance". The ... 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 ...
Regulatory T cell
The contribution of these populations to self-tolerance and immune homeostasis is less well defined. Foxp3 can be used as a ... Sakaguchi S, Yamaguchi T, Nomura T, Ono M (2008). "Regulatory T cells and immune tolerance". Cell. 133 (5): 775-87. doi:10.1016 ... The immune system must be able to discriminate between self and non-self. When self/non-self discrimination fails, the immune ... Sakaguchi S (2004). "Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune ...
Immune tolerance. Main article: Immune tolerance. The body naturally does not launch an immune system attack on its own ... Immune tolerance therapies seek to reset the immune system so that the body stops mistakenly attacking its own organs or cells ... Immune suppression dampens an abnormal immune response in autoimmune diseases or reduces a normal immune response to prevent ... Rotrosen D, Matthews JB, Bluestone JA (July 2002). "The immune tolerance network: a new paradigm for developing tolerance- ...
These selection processes allow for tolerance of self by the immune system. Typical T cells that leave the thymus (via the ... The T lymphocyte activation pathway: T cells contribute to immune defenses in two major ways; some direct and regulate immune ... "Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape". Cancer ... bridge the adaptive immune system with the innate immune system. Unlike conventional T cells that recognize peptide antigens ...
The placenta and fetus are thus treated as sites of immune privilege, with immune tolerance. ... Further information: Immune tolerance in pregnancy. The placenta and fetus may be regarded as a foreign body inside the mother ... This is the same mechanism used by parasitic nematodes to avoid detection by the immune system of their host. ... However, the Placental barrier is not the sole means to evade the immune system, as foreign fetal cells also persist in the ...
It is one method of immune tolerance. Frank Macfarlane Burnet proposed autoreactive cells would be terminated before maturation ... Thus, the host develops a tolerance for this antigen, or a self tolerance. B and T lymphocytes are tested for their affinity ... Central tolerance prevents B and T lymphocytes from reacting to self. Thus, clonal deletion can help protect individuals ... This prevents recognition and destruction of self host cells, making it a type of negative selection or central tolerance. ...
History and naming of human leukocyte antigens
For more information please see immune tolerance). Where this goes wrong is when tissues are transferred to another person. ... In generating an immune response to an antigen, the B-cells go through a process of maturation, from surface IgM production, to ... These cells were later found to be one of two types of immune cells, the T-cells (named for their origin, the thymus). The ... The biggest weakness in Burnet's theory was that he had no explanation for how the body selected for immune cells that only ...
Bertoletti A, Gehring A. Immune response and tolerance during chronic hepatitis B virus infection. Hepatology Research. 2007;37 ... See also: Immune system. The body's first line of defence against viruses is the innate immune system. This comprises cells and ... Not all virus infections produce a protective immune response in this way. HIV evades the immune system by constantly changing ... Viral infections in animals provoke an immune response that usually eliminates the infecting virus. Immune responses can also ...
Mature sperm (and their antigens) arise long after immune tolerance is established in infancy. Therefore, since sperm are ... The function of the blood-testis barrier (red highlight in diagram above) may be to prevent an auto-immune reaction. ... Thus, the blood-testis barrier may reduce the likelihood that sperm proteins will induce an immune response, reducing fertility ... Injection of sperm antigens causes inflammation of the testis (auto-immune orchitis) and reduced fertility. ...
Tolerance is a fundamental property of the immune system. Tolerance involves non-self discrimination which is the ability of ... Autoimmunity can thus be defined simply as exceptions to the tolerance "rules." By doing this, an immune response is generated ... Tolerance is also produced in T cells. There are also various processes which lead to B cell tolerance. Just as in T cells, ... B cell tolerance then must occur within the periphery after the induction of B cell tolerance within the thymus as a more ...
Butyrophilin, subfamily 1, member A1
Lu M, Varley AW, Munford RS (2013). "Persistently active microbial molecules prolong innate immune tolerance in vivo". PLOS ... 2012). "Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA ... The LPS-exposed mice develop strikingly high titers of polyclonal antibodies, prolonged hepatomegaly, and innate immune " ... "tolerance" that gives them slow and inadequate responses to bacterial challenge. AOAH has been highly conserved through ...
CD4+ T cells and antitumor immunity
Their main functions involve maintaining self-tolerance and immune homeostasis. Treg differentiation is induced by expression ... Paradoxical effects of cytokines in tumor immune surveillance and tumor immune escape. Cytokine and Growth Factor Reviews 18, ... These T cells produce high levels of IL-10 and TGF-β, thereby suppressing the immune system and allowing for evasion by the ... Immune interferon: a pleiotropic lymphokine with multiple effects. Immunology Today 6:4, pp. 131-136 Wang, Rong-Fu., 2001. The ...
Nadeau's laboratory is working on scientific investigations of immune tolerance. Areas of research include: Primary immune ... During this time, she also did a postdoctoral fellowship in human immune tolerance mechanisms in asthma and allergy.[citation ... NIH 2014 National Scientific Committee of the Immune Tolerance Network, NIH 2015 Elected into American Society of Clinical ... Environmental effects on tolerance - Ambient air pollution, specifically polycyclic aromatic hydrocarbons found in diesel ...
C. Garrison Fathman
Co-Chairman of the Autoimmunity Committee of the Immune Tolerance Network; Naomi M. Kanof Award for Distinguished Achievement ... He was instrumental in helping develop the Human Immune Monitoring Center at Stanford University. Dr. Fathman received his M.D ... The Human Immune Monitoring Center - Research - Institute for Immunity, Transplantation and Infection - Stanford University ... Chairman NIH Immunological Sciences and Hyper-accelerated Award/Mechanisms in Immune Disease Study Sections, HHMI Review Panel ...
Rupert E. Billingham
It may thus be regarded as insufficient immune tolerance in pregnancy. Generally rhesus disease becomes worse with each ... Fetal blood (or umbilical cord blood) The direct Coombs test is used to confirm that the fetus or neonate has an immune ... The use of Rh immune globulin to prevent the disease in babies of Rh negative mothers has become standard practice, and the ... The mother has an intramuscular injection of anti-Rh antibodies (Rho(D) immune globulin). This is done so that the fetal rhesus ...
"Operational tolerance vs immune suppression, targeting the αβ TCR with TOL101". American Journal of Transplantation. 10 (Suppl ... but are also capable of modulating many other aspects of the immune system, often resulting in long-term broad spectrum immune ... Chatenoud L (2010). "Immune therapy for type 1 diabetes mellitus-what is unique about anti-CD3 antibodies?". Nature Reviews ... Beetz S, Wesch D, Marischen L, Welte S, Oberg HH, Kabelitz D (2008). "Innate immune functions of human gammadelta T cells". ...
Walter and Eliza Hall Institute of Medical Research
Macfarlane developed the ideas of clonal selection and acquired immune tolerance. Later, Professor Donald Metcalf discovered ... with its scientists making important discoveries in the control of immune system responses, cell cycle regulation and malaria. ... that he was awarded the Nobel Prize for Medicine in 1960 with Sir Peter Medawar for the discovery of immunological tolerance. ...
Immune tolerance therapies seek to reset the immune system so that the body stops mistakenly attacking its own organs or cells ... Immune suppression dampens an abnormal immune response in autoimmune diseases or reduces a normal immune response to prevent ... "The immune tolerance network: a new paradigm for developing tolerance-inducing therapies". The Journal of Allergy and Clinical ... Other drugs modulate immune responses. The body naturally does not launch an immune system attack on its own tissues. ...
The main reason for this success is increased immune tolerance during pregnancy. Immune tolerance is the concept that the body ... 1-4. doi:10.1007/0-387-34944-8. ISBN 978-0-387-34944-2. Williams, Zev (2012-09-20). "Inducing Tolerance to Pregnancy". New ... This is from factors including underdeveloped lungs of newborns, infection due to underdeveloped immune system, feeding ... is able to not mount an immune system response against certain triggers. Pregnancy is typically broken into three periods, or ...
These selection processes allow for tolerance of self by the immune system. Typical T cells that leave the thymus (via the ... bridge the adaptive immune system with the innate immune system. Unlike conventional T cells that recognize peptide antigens ... Their major role is to shut down T cell-mediated immunity toward the end of an immune reaction and to suppress autoreactive T ... Haynes BF, Markert ML, Sempowski GD, Patel DD, Hale LP (2000). "The role of the thymus in immune reconstitution in aging, bone ...
Liu K, Iyoda T, Saternus M, Kimura Y, Inaba K, Steinman RM (Oct 2002). "Immune tolerance after delivery of dying cells to ... Kim R, Emi M, Tanabe K (May 2007). "Cancer immunoediting from immune surveillance to immune escape". Immunology. 121 (1): 1-14 ... He reasoned, the immune system would be able to play a factor via a 'bystander effect' in eradicating chemotherapy-resistant ... Syn, Nicholas L; Teng, Michele W L; Mok, Tony S K; Soo, Ross A. "De-novo and acquired resistance to immune checkpoint targeting ...
Type 1 regulatory T cells (Tr1 cells)
... a new mechanism of peripheral immune tolerance". Cellular & Molecular Immunology. 12 (5): 566-571. doi:10.1038/cmi.2015.44. ... The suppressing and tolerance-inducing effect of Tr1 cells is mediated mainly by cytokines. The other mechanism as cell to cell ... Cytolysis indirectly suppresses immune response by reducing numbers of myeloid-origin antigen presenting cells. Tr 1 cells are ... Tr1 cells are self or non-self antigen specific and their key role is to induce and maintain peripheral tolerance and suppress ...
2015) Fezf2 Orchestrates a Thymic Programs of Self-Antigen Expression for Immune Tolerance. Cell 163, 975 - 987 Thymus ... If these peripheral tolerance mechanisms also fail, autoimmunity may arise. Thymus transplantation results in that T cells are ... If T cells bearing these T cell receptors were to enter the periphery, they would be capable of activating an immune response ... Additional mechanisms of peripheral tolerance active in the periphery exist to silence these cells such as anergy, deletion, ...
"Mechanisms of peripheral immune tolerance: Conversion of the immune to the unresponsive phenotype". Immunologic Research. 28 (3 ... December 1990). "Mechanisms of Autoimmunity in the Context of T-Cell Tolerance: Insights from Natural and Transgenic Animal ... Gupta, Sudhir; Paul, William E.; DeFranco, Anthony; Perlmutter, Roger (2013). Mechanisms of Lymphocyte Activation and Immune ...
No animal species is immune to the acute toxic effects of aflatoxins. Adult humans have a high tolerance for aflatoxin exposure ... Adults have a higher tolerance to exposure, but are also at risk. No animal species is immune. Aflatoxins are among the most ... Aflatoxin B1 can cause immune suppression, and exposure to it is associated with an increased viral load in HIV positive ...
T细胞 - 维基百科，自由的百科全书
Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer ... Autonomous role of medullary thymic epithelial cells in central CD4(+) T cell tolerance. Nature Immunology. 2010-06, 11 (6): ... Glycans in the immune system and The Altered Glycan Theory of Autoimmunity. J Autoimmun. 2015, 57 (6): 1-13. PMC 4340844. PMID ... Immunobiology: the immune system in health and disease 5th ed. New York: Garland Pub. 2001. ISBN 978-0-8153-3642-6. OCLC ...
drug sensitization or reverse tolerance - the escalating effect of a drug resulting from repeated administration at a given ... 2001). Immunobiology 5: The Immune System in Health and Disease. New York: Garland Pub., ISBN 0-8153-3642-X ... tolerance - the diminishing effect of a drug resulting from repeated administration at a given dose ... the opposite of drug tolerance). Such sensitization involves changes in brain mesolimbic dopamine transmission, as well as a ...
Marchand F, Perretti M, McMahon SB (July 2005). "Role of the immune system in chronic pain". Nat. Rev. Neurosci. 6 (7): 521-32 ... DuPen A, Shen D, Ersek M (September 2007). "Mechanisms of opioid-induced tolerance and hyperalgesia". Pain Manag Nurs. 8 (3): ... This seems to occur via immune cells interacting with the peripheral nervous system and releasing pain-producing chemicals ( ... As it can be difficult to distinguish from tolerance, opioid-induced hyperalgesia is often compensated for by escalating the ...
Faktor aktivacije B-ćelija
Antibody - Simple English Wikipedia, the free encyclopedia
10.0 10.1 10.2 Market E & Papavasiliou FN (2003). "V(D)J recombination and the evolution of the adaptive immune system". PLoS ... Nemazee D (2006). "Receptor editing in lymphocyte development and central tolerance". Nat Rev Immunol 6 (10): 728-40. doi: ... Using this binding mechanism, an antibody can tag a microbe or an infected cell for attack by other parts of the immune system ... Each of these variants can bind to a different antigen. This enormous diversity of antibodies allows the immune system to ...
T細胞 - 維基百科，自由的百科全書
顆粒白血球 - 維基百科，自由的百科全
White blood cell
Inherited immune deficiency - severe combined immunodeficiency, common variable immune deficiency, ataxia-telangiectasia, ... White blood cells (also called leukocytes or leucocytes and abbreviated as WBCs) are the cells of the immune system that are ... This article is about the cells of the immune system also known as white blood cells. For the album by the band the White ... Immune dysfunction - arthritis, systemic lupus erythematosus, Sjögren syndrome, myasthenia gravis, systemic vasculitis, Behcet- ...
T independent antigen (TI)
Immature B cells are anergized, so they do not elicit any immune response. That may explain why children up to 5 years are not ... The most commonly released isotype of antibodies in this type of immune reaction is low affinity IgM. ... This part of immune response may be important in some early stages of infection by extracellular pathogens, because it is ...
Urinary tract infection
Long-term tolerance is also an issue with gastrointestinal upset occurring in more than 30%. Cranberry juice is thus ... Coli are able to attach to the bladder wall and form a biofilm that resists the body's immune response. ... "The nature of immune responses to urinary tract infections". Nature Reviews. Immunology. 15 (10): 655-663. doi:10.1038/nri3887 ...
List of atheists in science and technology
He won the Nobel Prize in 1960 for predicting acquired immune tolerance and was best known for developing the theory of clonal ... "His tolerance and good humour enabled him to disagree strongly without giving or taking offence, for example with his brother ... He is best known for his research into the immune system. Mechnikov received the Nobel Prize in Medicine in 1908, shared with ... Sir Peter Medawar (1915-1987): Nobel Prize-winning British scientist best known for his work on how the immune system rejects ...
While tolerance may limit the maximal effects of certain drugs, evidence suggests that tolerance develops irregularly for ... mainly expressed in cells of the immune system. The psychoactive effects of THC are primarily mediated by the activation of ... this form of tolerance appears to be irregular throughout mouse brain areas. THC, as well as other cannabinoids that contain a ...
... function of the immune system (ID 134), function of the immune system during and after extreme physical exercise (ID 144), non- ... September 13, 2010). Ascorbate-Glutathione Pathway and Stress Tolerance in Plants. Springer. p. 324. ISBN 978-9-048-19403-2. . ... Wintergerst ES, Maggini S, Hornig DH (2006). "Immune-enhancing role of vitamin C and zinc and effect on clinical conditions". ... Vitamin C distributes readily in high concentrations into immune cells, has antimicrobial and natural killer cell activities, ...
Each antibody is specifically produced by the immune system to match an antigen after cells in the immune system come into ... as the quality of the T cell pool that is available for these antigens is not affected by central T cell tolerance. Technology ... It first initiates an innate immune response, which then causes the activation of the adaptive immune response. An antigen ... In order to induce an immune response, it needs to be attached to a large carrier molecule such as a protein (a complex of ...
Immune systemEdit. Though most attention is focused on PrP's presence in the nervous system, it is also abundant in immune ... could stem from the tolerance for PrPSc. ... PrP immune cells include hematopoietic stem cells, mature ... "The role of the cellular prion protein in the immune system". Clin. Exp. Immunol. 146 (1): 1-8. doi:10.1111/j.1365-2249.2006. ...
When immune cells encounter the allergenic protein, IgE antibodies are produced; this is similar to the immune system's ... Tolerance of a cow's milk-based hydrolyzed formula in patients with eosinophilic esophagitis triggered by milk. Allergy; 68: ... A food allergy is an abnormal immune response to food. The symptoms of the allergic reaction may range from mild to severe.[ ... Glucocorticoid steroids are used to calm down the immune system cells that are attacked by the chemicals released during an ...
Although it is not yet well understood, IgE may play an important role in the immune system's recognition of cancer, in ... Erb KJ (2007). "Helminths, allergic disorders and IgE-mediated immune responses: where do we stand?". Eur. J. Immunol. 37 (5): ... to allow other immune cells to gain access to tissues, but which can lead to a potentially fatal drop in blood pressure as in ... IgE is utilized during immune defense against certain protozoan parasites such as Plasmodium falciparum. ...
Kasutaja:Mariina/Lapseea aktiivsus- ja tähelepanuhäire - Vikipeedia
Posttraumatic stress disorder
His resentment fed his discontent with official policies of tolerance; from 302 on, he probably urged Diocletian to enact a ... "Gaul was immune" (immunis est Gallia) from the persecutions under Constantius. The death of Saint Alban, the first British ... still had tendencies towards religious tolerance.[notes 13] Galerius, by contrast, was a devoted and passionate pagan. ...
Single cell sequencing
The single-cell yeast study sought to characterize the heterogeneous stress tolerance in isogenic yeast cells before and after ... "Pathogen Cell-to-Cell Variability Drives Heterogeneity in Host Immune Responses". Cell. 162 (6): 1309-21. doi:10.1016/j.cell. ... "Predicting bacterial infection outcomes using single cell RNA-sequencing analysis of human immune cells". Nature ...
... , also known as hay fever, is a type of inflammation in the nose which occurs when the immune system ... thereby inducing specific long-term tolerance. Allergy immunotherapy can be administered orally (as sublingual tablets or ... Immune mechanisms of allergen-specific sublingual immunotherapy. Revue française d'allergologie et d'immunologie clinique. 2006 ...
An improperly functioning immune system can cause discomfort, disease or even death. The type of malfunction falls into one or ... Therefore, one of the most important roles of the thymus is the induction of central tolerance. The thymus is largest and most ... No other immune cell lineages are affected by the congenital absence of the thymus. DiGeorge syndrome is the most common ... The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, T cells mature. T cells are ...
Immune tolerance - Wikipedia
Immune Tolerance Network International Conference on Immune Tolerance Immune tolerance at the US National Library of Medicine ... Immune tolerance is important for normal physiology. Central tolerance is the main way the immune system learns to discriminate ... Immune tolerance, or immunological tolerance, or immunotolerance, is a state of unresponsiveness of the immune system to ... see Immune response). Tolerance is classified into central tolerance or peripheral tolerance depending on where the state is ...
Astellas sets up immune tolerance JV in $760m deal - PharmaTimes
760 million to create a new US-based firm focused on developing novel immune tolerance therapeutics. - News - PharmaTimes ... The firm will utilise Anokions tolerance-inducing technology shown to induce immune tolerance to protein drugs and autoimmune ... Astellas sets up immune tolerance JV in $760m deal. 3rd June 2015. ... 760 million to create a new US-based firm focused on developing novel immune tolerance therapeutics. ...
Uncovering the role of the placenta in pregnancy immune tolerance - AgBioResearch
Margaret Petroff believes that decoding additional secrets to immune tolerance could lead to treatment breakthroughs for a ... His research eventually homed in on immune tolerance, the biological process that allows the hosts immune system to accept ... "If we can better understand the function of the placenta during pregnancy and how that promotes immune tolerance, we can combat ... Uncovering the role of the placenta in pregnancy immune tolerance. Margaret Petroff believes that decoding additional secrets ...
Searching For The Secrets Of Drug-Free Transplants: University Of Pittsburgh, Through Immune Tolerance Network, To Develop...
Through Immune Tolerance Network, To Develop Tests Predictive Of Transplant Tolerance ... searching-secrets-drug-free-transplants-university-pittsburgh-immune-tolerance-network-develop-tests-transplant-tolerance ... Through Immune Tolerance Network, To Develop Tests Predictive Of Transplant Tolerance. PITTSBURGH, November 1, 2000 - ... Transplant tolerance, which refers to the state by which a patients immune system has fully accepted a transplanted organ, is ...
... immune stimulus) or group of antigens to which a person is normally responsive. Immune tolerance can result from a number of ... Immune tolerance in pregnancy - or gestational/maternal immune tolerance is the absence of a maternal immune response against ... Tolerance (disambiguation) - Tolerance may refer to:* Tolerance, a virtue or value * Religious tolerance, tolerance toward ... Immune tolerance - or immunological tolerance is the process by which the immune system does not attack an antigen. It can ...
4th Antigen Specific Immune Tolerance Digital Summit
The 4th Antigen Specific Immune Tolerance Digital Summit (ASIT) brings together industry representatives from the fields of ... 4th Antigen Specific Immune Tolerance Digital Summit. ×. 4th Antigen Specific Immune Tolerance Digital Summit Gallery. ... Antigen Specific Immune Tolerance Summit Team. Phone:. N/A. E-mail:. [email protected] Filed in:. Things to do near Dearing ... The 4th Antigen Specific Immune Tolerance Digital Summit (ASIT) brings together industry representatives from the fields of ...
Speakers | Antigen Specific Immune Tolerance | Feb 25-27 | Boston
... to realizing the commercial potential of antigen specific immunotherapies with a focus on novel approaches to tolerance ... 2:00 pm , The Importance of Tolerance Delivery Systems in Antigen-Specific Immune Tolerance ... He is Co-Founder of Cellerys AG, a company developing a cell based therapy to induce immune tolerance in MS. The group has ... Within the antigen-specific immune tolerance space, he has been involved as PI or mentor in three proof-of-concept clinical ...
Details of N01AI15416-26-0-4: Immune tolerance network: type 1 diabetes
... the immune system to eliminate injurious immune responses. The ITN is conducting clinical trials in autoimmune diseases such as ... In addition, to understand the underlying mechanisms of action of the candidate therapies and to monitor tolerance, the ITN has ... The Immune Tolerance Network is dedicated to the clinical evaluation of novel tolerance-inducing therapies that will ¿re- ... Immune Tolerance Network: Multiple Sclerosis. California Univ San Franc. 2012. $6,691,934. Immune Tolerance Network: Type 1 ...
The development of tolerance is the result of active immune mechanisms and both development and maintenance of tolerance are ... The immune system also acts to ensure tolerance to self, to food and other environmental components, and to commensal ... immune maturation and immune responses. Through these mechanisms it is possible that nutrition early in life might affect later ... If the neonatal immune system is not able to down-regulate the pre-existing Th2 dominance effectively then an allergic ...
Immune tolerance - Wikipedia
Immune tolerance, or immunological tolerance, or immunotolerance, is a state of unresponsiveness of the immune system to ... Tradeoffs between immune tolerance and resistance. Immune tolerance contrasts with resistance. Upon exposure to a foreign ... International Conference on Immune Tolerance. *Immune+tolerance at the US National Library of Medicine Medical Subject Headings ... Immune tolerance is important for normal physiology. Central tolerance is the main way the immune system learns to discriminate ...
Immune tolerance in pregnancy - Wikipedia
Immune tolerance in pregnancy or gestational/maternal immune tolerance is the absence of a maternal immune response against (in ... and a chronic insufficient tolerance may cause infertility. Other examples of insufficient immune tolerance in pregnancy are Rh ... The increased immune tolerance is believed to be a major contributing factor to an increased susceptibility and severity of ... immune tolerance towards) the fetus and placenta during pregnancy, which thus may be viewed as unusually successful allografts ...
Category:Immune tolerance - Wikimedia Commons
Media in category "Immune tolerance". The following 25 files are in this category, out of 25 total. ... Native-cellulose-nanofibrills-induce-immune-tolerance-in-vitro-by-acting-on-dendritic-cells-srep31618-s2.ogv 12 s, 1,440 × ... Native-cellulose-nanofibrills-induce-immune-tolerance-in-vitro-by-acting-on-dendritic-cells-srep31618-s3.ogv 12 s, 640 × 480; ... Native-cellulose-nanofibrills-induce-immune-tolerance-in-vitro-by-acting-on-dendritic-cells-srep31618-s4.ogv 12 s, 1,440 × ...
... is a state in which the immune system does not reject the donor organ while still responding to challenges ... We are translating basic studies into two clinical trials of tolerance in liver transplantation: the Liver Immune Tolerance ... In the Liver Immune Tolerance Marker Utilization Study (LITMUS, NCT NCT02541916), we gradually wean patients off their ... Liver Immune Tolerance Marker Utilization Study (LITMUS, NCT NCT02541916). Studies with random withdrawal of immunosuppression ...
Gut Immune Tolerance | Science Signaling
... the gut is an important site of immune tolerance. By studying specific intestinal immune cell populations in genetically ... Myeloid cells, innate lymphoid cells, and the cytokines they secrete cooperate to maintain immune tolerance in the gut. ... Myeloid cells, innate lymphoid cells, and the cytokines they secrete cooperate to maintain immune tolerance in the gut. ... a population of cells known to be critical for maintaining immune tolerance in the gut. ...
New MS Treatment 'Tricks' Immune System | Myelin Tolerance | Live Science
"Therefore, rather than inducing an immune response, they actually induce tolerance.". The patients in the study received ... the researchers found that patients who received the highest doses of the treatment showed enhanced immune tolerance for myelin ... "The immune system has evolved in such a way that apoptotic cells are not seen as a threat," Miller said. " ... Myelin is made of different proteins, and which ones are targeted by the immune system can vary in different MS patients, and ...
Antigen-specific immune tolerance drug development summit | EurekAlert! Science News
Immune Tolerance Induction Study - Full Text View - ClinicalTrials.gov
Immune Tolerance Induction Study. The safety and scientific validity of this study is the responsibility of the study sponsor ... An Exploratory Study of the Safety and Efficacy of Immune Tolerance Induction (ITI) in Patients With Pompe Disease Who Have ... safety and clinical benefit of 2 Immune Tolerance Induction (ITI) regimens in combination with Myozyme. Eligible patients who ...
Research institute acquires Immune Tolerance Institute - CenterWatch News Online
Home » News » R&D Trends » Research institute acquires Immune Tolerance Institute Research institute acquires Immune Tolerance ... The David H. Murdock Research Institute (DHMRI) has acquired the Immune Tolerance Institute (ITI) as part of the North Carolina ... "Advancing immune science will lead to new approaches to investigate the biological mechanisms of disease and functional ... Institutes mission to accelerate the discovery and development of breakthrough treatments for a range of immune-related ...
Immune tolerance ensures that the immune system responds to foreign molecules and not to self-molecules. When tolerance breaks ... Immune Tolerance. Subject Area(s): Human Biology and Disease; Immunology and Vaccines. Edited by Diane J. Mathis, Harvard ... Central B-Cell Tolerance: Where Selection Begins. Roberta Pelanda and Raul M. Torres. Natural Killer Cell Tolerance: Control by ... Understanding the mechanisms involved in establishing and maintaining immune tolerance is essential for effectively treating ...
Review major scientific findings in Immune Tolerance and how our cell isolation and cell separation products support these ... Central Tolerance Peripheral Tolerance Central Tolerance. Multiple mechanisms of central tolerance take place in the thymus, ... Central tolerance prevents the maturation and egress of autoreactive immune cells, for example via clonal deletion of T cells ... Immune tolerance is critical to prevent the development of autoimmune and inflammatory diseases. There are several mechanisms ...
Tolerance and immune suppression in the tumor microenvironment
Ray Owens ground-breaking observations in twin cattle provided the first mechanistic explanation for tolerance to self- ... molecules and established tolerance as a beneficial process that protects the host agains … ... The concept of immunological tolerance has guided and permeated much of modern immunology. ... Tolerance and immune suppression in the tumor microenvironment Cell Immunol. 2016 Jan;299:23-9. doi: 10.1016/j.cellimm.2015.09. ...
Immune Tolerance - Fraunhofer IZI
Pregnancy: tolerance and suppression of immune responses.
Presence of foreign tissue in a hosts body would immediately lead to a strong immune response directed to destroy the ... Immune Tolerance / immunology*. Isoantigens / immunology*. Killer Cells, Natural / immunology. Mast Cells / immunology. ... the semiallogeneic fetus is allowed to grow within the maternal uterus due to multiple mechanisms of immune tolerance, which ... Presence of foreign tissue in a hosts body would immediately lead to a strong immune response directed to destroy the ...
Celiac disease might be cured by restoring immune tolerance to gliadin | EurekAlert! Science News
Loss of tolerance to gliadin is caused by a failure in the regulation of gliadin-specific T lymphocytes within the immune ... These predispositions may lead to the loss of immune tolerance to gliadin during childhood, adolescence or adulthood. ... Celiac disease might be cured by restoring immune tolerance to gliadin. University of Helsinki ... Gliadin nanoparticle treatment also induced gene expression profiles associated with immune tolerance. These findings support ...
Rituximab and immune tolerance in severe hemophilia A: a consecutive national cohort. - PubMed - NCBI
Rituximab and immune tolerance in severe hemophilia A: a consecutive national cohort.. Collins PW1, Mathias M, Hanley J, ... resistant to standard immune tolerance is challenging. There have been recent case reports of the successful use of rituximab ... of patients as part of rescue immune tolerance regimens. Because case reports and small series are prone to the potential bias ... combined with FVIII is a potentially useful treatment for patients with inhibitors resistant to standard immune tolerance, ...
Patente US9295756 - Methods for inducing immune tolerance to organ transplants - Google Patentes
The immune tolerance is achieved by selective ablation of the inner lining of the blood vessels of the organ or tissue, in a ... Accordingly, the present invention relates to novel methods for inducing immune tolerance to tissue or organ transplants by ... Methods for inducing immune tolerance to organ transplants. ... Methods for inducing immune tolerance to organ transplants. US ... For example, the tolerance may be assessed by monitoring subject-specific leukocyte or T-lymphocyte infiltration of the graft, ...
NIH Guide: COLLABORATIVE NETWORK FOR CLINICAL RESEARCH ON IMMUNE TOLERANCE
COLLABORATIVE NETWORK FOR CLINICAL RESEARCH ON IMMUNE TOLERANCE Release Date: January 22, 1999 RFP AVAILABLE: NIH-NIAID-DAIT-99 ... coordinate and manage a Collaborative Network for Clinical Research on Immune Tolerance. The goals of this Collaborative ... maintenance and loss of tolerance as an integral part of Network-sponsored clinical trials, as well as clinical trials ... design a long-term research agenda to accelerate the application of tolerogenic approaches for the treatment of multiple immune ...
Implication of Regulatory Cells on Immune Tolerance - Nova Science Publishers
Home / Shop / Books / Science and Technology / Life Sciences / Implication of Regulatory Cells on Immune Tolerance. ... Implication of Regulatory Cells on Immune Tolerance. Carol Aristimuño, Roseta Teijeiro, Clara de Andrés and Silvia Sánchez- ... Central tolerance occurs very early in the development at the primary lymphoid organs, the thymus and the bone marrow for T and ... ISBN: N/A Categories: Immunology and Immune System Disorders, Cell Biology Research Progress, Cell Biology, Biology, Life ...
JCI - microRNA-142-mediated repression of phosphodiesterase 3B critically regulates peripheral immune tolerance
Tregs play a fundamental role in immune tolerance via control of self-reactive effector T cells (Teffs). This function is ... In this study, we demonstrate that peripheral immune tolerance is critically dependent on posttranscriptional repression of the ... microRNA-142-mediated repression of phosphodiesterase 3B critically regulates peripheral immune tolerance. ... microRNA-142-mediated repression of phosphodiesterase 3B critically regulates peripheral immune tolerance. ...
JCI - Mechanisms of immune tolerance to allergens: role of IL-10 and Tregs
The demonstration of T cell tolerance, particularly that mediated by the immune-suppressive functions of IL-10, led to a major ... Mechanisms of immune tolerance to allergens: role of IL-10 and Tregs. ... Mechanisms of immune tolerance to allergens: role of IL-10 and Tregs. ... Currently, the known essential components of allergen tolerance include the induction of allergen-specific regulatory subsets ...
'immune tolerance' Protocols and Video...
... immune tolerance include Isolation of Sertoli Cells and Peritubular Cells from Rat Testes, Sexual Transmission of American ... Human In Vitro Suppression as Screening Tool for the Recognition of an Early State of Immune Imbalance, A Mouse Model of in ... Immune Tolerance: The specific failure of a normally responsive individual to make an immune response to a known antigen. It ... Human In Vitro Suppression as Screening Tool for the Recognition of an Early State of Immune Imbalance. Jill Waukau1, Jeffrey ...
Browsing Publications by Subject "Immune Tolerance"
Medical Xpress - immune tolerance
Study reveals how to reprogram cells in our immune system. When the immune system is imbalanced, either due to overly-active ... For a pregnancy to proceed to term, early modulation of the immunologic response is required to induce tolerance to the fetus. ... have devised a novel DNA vaccine approach through molecular design to improve the immune responses elicited against one of the ... Researchers have identified a brain mechanism that could be a drug target to help prevent tolerance and addiction to opioid ...
Interactions among dendritic cells, macrophages, and epithelial cells in the gut: implications for immune tolerance. - PubMed ...
Interactions among dendritic cells, macrophages, and epithelial cells in the gut: implications for immune tolerance.. Rescigno ... clear that this tolerance is a complex process that derives from the coordinated action of both canonical immune and non-immune ... Understanding how tolerance is achieved at mucosal sites may thus be exploited to re-establish tissue homeostasis. ... Additionally, tolerance to ingested antigens promotes the development of systemic unresponsiveness towards the same antigens. ...
Adenovirus-Mediated CCR7 and BTLA Overexpression Enhances Immune Tolerance and Migration in Immature Dendritic Cells
Our study provides a basis for further studies on imDCs in immune tolerance, with the goal of developing effective cellular ... In the present study, we aimed to investigate whether BTLA overexpression was sufficient to preserve immune tolerance in imDCs ... Adenovirus-Mediated CCR7 and BTLA Overexpression Enhances Immune Tolerance and Migration in Immature Dendritic Cells. Haiming ... All these results indicated that adenovirus-mediated CCR7 and BTLA overexpression could enhance immune tolerance and migration ...
E3 Ligases in T Cell Anergy-Turning Immune Responses into Tolerance | Science Signaling
E3 Ligases in T Cell Anergy-Turning Immune Responses into Tolerance Message Subject. (Your Name) has forwarded a page to you ... Peripheral tolerance is an important strategy used by the immune system to prevent self-reactive lymphocytes from attacking ... A variety of mechanisms contribute to peripheral tolerance, among them activation-induced cell death, suppression by regulatory ...
Prostaglandin E2 and SOCS1 have a role in intestinal immune tolerance. | Sigma-Aldrich
Prostaglandin E2 and SOCS1 have a role in intestinal immune tolerance.. [Takatoshi Chinen, Kyoko Komai, Go Muto, Rimpei Morita ... Here, we identify suppressor of cytokine signalling 1 (SOCS1) as an essential mediator of immune tolerance in the intestine. ... Additionally, we find an essential role for prostaglandin E2 (PGE2) in the maintenance of tolerance within the intestine in the ... Thus, we propose that SOCS1 and PGE2, potentially interacting together, act as an alternative intestinal tolerance mechanism ...
AntigensImmunologicalAntigen-specificInduceTransplantationCellsResponseInductionSystemPhysiologicalResponsesAutoimmune DiseasesLymphocytesRegulatoryInduce immune toleranceAutoimmunityType 1 DiabetImmunologyTransplantationTumorTherapeuticsAntigen-specific immune toleranceSystem'sImmunityTransplantImmunosuppressionPathwaysRestores immune toClinicalTregHumansImmunotherapyTumorsCell toleranceMiceInhibitorsSpecific immuneMechanisms of immuneTolerogenicEfficacyIntestinalInduction therapyEstablishment of Immune ToleranceAllergensSuppressorDiseasesAntibodies
- The 4th Antigen Specific Immune Tolerance Digital Summit (ASIT) brings together industry representatives from the fields of autoimmunity, allergy, immuno-oncology and transplantation to tackle the complexities behind autoimmune disorders head on. (eventsnearhere.com)
- Across 3 packed days, thought leaders from Novartis, ImCyse, Harvard Medical School, Toleranzia, Toralgen will reveal insight, data, and lessons learned from the last 12 months to enable you to hurdle the roadblocks preventing the development of clinically safe and effective antigen-specific immunotherapies for autoimmune and immune mediated disorders. (eventsnearhere.com)
- His work has focused on the study of the cellular and molecular mechanisms underlying treatment of established T cell-mediated autoimmune diseases using antigen-specific immune tolerance. (as-immunetolerance.com)
- He is Co-Founder of Cellerys AG, a company developing a cell based therapy to induce immune tolerance in MS. The group has recently closed a successful phase Ib trial using myelin-peptide coupled red blood cells to induce immune tolerance in MS patients and is continuing the clinical development the approach for treatment of MS. (as-immunetolerance.com)
- 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. (utmb.edu)
- We propose a model of antigen-induced tolerance that involves cell-cell contact with regulatory CD4 + T cells that coexpress membrane-bound TGF-β and FOXP3. (utmb.edu)
- It is used to describe the phenomenon underlying discrimination of self from non-self, suppressing allergic responses, allowing chronic infection instead of rejection and elimination, and preventing attack of fetuses by the maternal immune system. (wikipedia.org)
- The basic premise of the eu-FEDS hypothesis is that both soluble and cell surface associated glycoproteins, present in the reproductive system and expressed on gametes, suppress any potential immune responses, and inhibit rejection of the fetus. (wikipedia.org)
- Pregnancy: tolerance and suppression of immune responses. (biomedsearch.com)
- Currently, the known essential components of allergen tolerance include the induction of allergen-specific regulatory subsets of T and B cells, the immune-suppressive function of secreted factors, such as IL-10 and TGF-β, the production of IgG4 isotype allergen-specific blocking antibodies, and decreased allergic inflammatory responses by mast cells, basophils, and eosinophils in inflamed tissues. (jci.org)
- This Research Topic focuses on such targeted antigen delivery approaches aimed at promoting immune tolerance in autoimmune diseases, transplantation, allergy, and immunogenic responses to biologics. (frontiersin.org)
- However, important questions remain about the events that lead to the loss of B- and T-cell tolerance and the inadequacy of regulatory mechanisms to restrain β-cell-specific responses. (diabetesjournals.org)
- Although the timing of such responses remains unclear, mounting evidence implicates the formation of neoepitopes as a relevant means of disrupting β-cell tolerance. (diabetesjournals.org)
- The GFP/luc signals serve a dual purpose: they act as potent neoantigens capable of stimulating leukemia-specific immune responses and a bioluminescent reporter for the highly sensitive detection of minimal residual disease (MRD). (chop.edu)
- The immune system 's reaction to antigen depends on (a) the relative frequencies of responding T and B cells and on the thresholds of the binding affinity that their receptors display, (b) the levels of antigen present, and (c) the period during which the antigen remains in secondary lymphoid tissue, where primary immune responses are initiated. (fitness-vip.com)
- SUMMARY: Modern dietary changes are clearly implicated in the rising propensity for inflammatory immune responses. (diva-portal.org)
- Therefore, nanoparticles entering the body, after interaction with proteins, will be either recognized as self-agents or detected by the immune system, encompassing immunostimulation or immunosuppression responses. (spie.org)
- Additionally, it opens up the possibility to modulate the immune response in order to suppress unwanted responses resulting from autoimmunity, or allergy or to stimulate protective responses against pathogens. (spie.org)
- and understand how Egr2 and 3 expressions are regulated under tumour microenvironment, which may provide the potential bio-marks for tumour immune responses, and new strategy for individual immunotherapy of cancer patients. (findaphd.com)
- HSPs may play yet more fundamental roles in immune responses because of a series of surprising findings that they can modulate the functions of DCs in a receptor-dependent manner. (aacrjournals.org)
- The initial clues were derived largely from the analysis of the responses of the immune system to a purified endoplasmic reticular HSP, gp96 ( 26 ). (aacrjournals.org)
- The immune system has evolved regulatory mechanisms in order to balance the effects of deleterious immune responses. (dissertations.se)
- As T1D mainly affects children and young adults, any candidate immune therapy must be safe, and it must avoid a sustained depression of immune responses with all its attendant problems of recurrent infection and drug toxicity. (soc-bdr.org)
- Vaccination with a heat-killed recombinant yeast expressing the tumor-associated antigen CEA induces CEA-specific immune responses, reduces tumor burden, and extends overall survival in CEA-Tg mice. (aacrjournals.org)
- It has been shown that S. cerevisiae and other yeast species initiate immune responses by inducing maturation of dendritic cells. (aacrjournals.org)
- Because of this ability to induce robust immune responses, several studies have been conducted using S. cerevisiae as a vaccine vehicle. (aacrjournals.org)
- Rapamycin (R) and prednisone (P) are immunosuppressants with a regulatory T-cell sparing effect, and both are used clinically to suppress cytotoxic immune responses. (queensu.ca)
- It is known that ultraviolet B light(UV) impairs the induction phase of contact hypersensitivity responses(CHS) and subsequently induces tolerance. (nii.ac.jp)
- Innate immune responses are evolutionarily conserved processes that provide crucial protection against invading organisms. (biomedcentral.com)
- Gene expression profiling revealed that Drosophila Nub negatively regulates many genes that are involved in immune and stress responses, while it is a positive regulator of genes involved in differentiation and metabolism. (biomedcentral.com)
- We suggest that Nub protein plays an ancient role, shared with mammalian Oct/POU transcription factors, to moderate responses to immune challenge, thereby increasing the tolerance to biotic stress. (biomedcentral.com)
- Understanding the mechanisms involved in establishing and maintaining immune tolerance is essential for effectively treating these autoimmune diseases. (cshlpress.com)
- The goals of this Collaborative Network are to: (1) design a long-term research agenda to accelerate the application of tolerogenic approaches for the treatment of multiple immune system diseases, including autoimmune diseases, asthma and allergic diseases, and graft rejection on solid organ, cell and tissue transplantation. (nih.gov)
- Tolerance assays could support a number of clinical trials and might provide important clues to understanding how tolerance impacts autoimmune diseases as well as allergy and asthma,' said Adriana Zeevi, Ph.D., professor of pathology and surgery at the university's Starzl Institute and co-principal investigator with Dr. Thomson. (upmc.com)
- The Immune Tolerance Institute (ITI) is a 501 (c)(3) non-profit corporation founded to fill critical unmet needs for translating fundamental scientific discoveries into new therapies for the broad range of diseases related to the human immune system, including autoimmune diseases, allergy, asthma, cancer, and cardiovascular and infectious diseases. (bio-medicine.org)
- While GARP is implicated in immune invasion in cancer, the roles of the GARP-TGF-β axis in systemic autoimmune diseases are unknown. (jci.org)
- However, these discoveries, and the host of allograft experiments and observations of twin chimerism they inspired, were seminal for the theories of immune tolerance formulated by Sir Frank McFarlane Burnet and Frank Fenner , who were the first to propose the deletion of self-reactive lymphocytes to establish tolerance, now termed clonal deletion . (wikipedia.org)
- Loss of tolerance to gliadin is caused by a failure in the regulation of gliadin-specific T lymphocytes within the immune system, leading to the destruction of the intestinal mucosa. (eurekalert.org)
- These findings support the concept that it may be possible to "reprogram" the immune system in celiac patients, and to instruct T lymphocytes to tolerate gluten again. (eurekalert.org)
- This thesis work is based on investigations of different tolerance mechanisms induced in CD4+ T lymphocytes in vivo. (dissertations.se)
- It is caused by an immune-mediated inflammation, involving autoreactive CD4 + and CD8 + T lymphocytes that infiltrate the islets and initiate insulitis. (soc-bdr.org)
- However, successful translation of novel mechanistic discoveries into effective immunotherapy was hindered by a number of obstacles, among them the ability of tumors to tolerize host lymphocytes rendering them functionally incompetent and the tumors ability to evade antigen-specific immune recognition through a variety of genetic, epigenetic, and stromal factors. (eurekaselect.com)
- Csf-2, in turn, induces myeloid cells (including dendritic cells and macrophages) to produce regulatory factors like retinoic acid and IL-10, which support the conversion and expansion of regulatory T cells, a population of cells known to be critical for maintaining immune tolerance in the gut. (sciencemag.org)
- Multiple mechanisms of central tolerance take place in the thymus, where self-reactive T cells undergo clonal deletion or differentiation into regulatory T cells (Tregs) 1 . (stemcell.com)
- Interleukin 10 (IL-10) and regulatory T cells (Tregs) maintain tolerance to intestinal microorganisms. (sigmaaldrich.com)
- However, important unanswered questions remain regarding the events that surround the initial loss of tolerance and subsequent failure of regulatory mechanisms to arrest autoimmunity and preserve functional β-cells. (diabetesjournals.org)
- Within the tumor stroma VEGF-C recruited a more regulatory immune cell infiltrate including increased regulatory T cells (CD25+FoxP3+) and M2 macrophages (CD11b+CD80-CD206+) and decreased antigen specific cytotoxic T cells (CD8+Trp2+). (aacrjournals.org)
- The main role is played by T regulatory (Treg) cells, which attempt to regulate and adapt the immune system of the mother to the new conditions of pregnancy. (hindawi.com)
- The cornerstone of the relationship between the immune system in pregnancy and the immune system in SLE is represented by T regulatory (Treg) cells. (hindawi.com)
- Another mechanism of immune tolerance is derived from regulatory T cells (Treg). (fitness-vip.com)
- Dr. Thomson's research interests have focused on the role of dendritic cells in tolerance, while Dr. Zeevi has been performing genetic analyses of key regulatory proteins within the immune system, where small changes in the code may reveal a patient's potential for rejection. (upmc.com)
- Increased macrophage phagocytosis of antibody-coated platelet as well as decreased number and/or impaired function of CD4 + CD25 + Foxp3 + regulatory T (Treg) cells have been shown to participate in the pathogenesis of immune thrombocytopenia (ITP). (bloodjournal.org)
- To pin down those details, the two scientists began looking at the immune system's T regulatory cells (Tregs) in a strain of inbred mice that are all genetically identical-except for one seemingly tiny detail. (scitech-news.com)
- The work described in the PNAS article, "Pregnancy induces a fetal antigen-specific maternal T regulatory cell response that contributes to tolerance," was supported in part by a research grant from the Skirball Foundation. (scitech-news.com)
- We have also shown that CD4+ T cells with regulatory functions may be induced after tolerance induction in vivo. (dissertations.se)
- However, whether PD-1 expression by the Treg cells is required for their immune regulatory function, especially in autoimmune settings, is still unclear. (nii.ac.jp)
- Foxp3 hCD2 reporter mouse line and an ablative anti-hCD2 antibody to ask if CD4 + FOXP3 + regulatory T cells (Treg) are required for coreceptor and costimulation blockade-induced immune tolerance. (biomedcentral.com)
Induce immune tolerance4
- Allergen immunotherapy is, under the control of the allergen (antigen) physician administered to the patient, in an attempt to induce immune tolerance and, with respect to food allergies (Patent Document 1 and 2) oral immunotherapy, mite allergic to pollen (Patent Document 3) immunotherapy sublingual, and transdermal immunotherapy known (Patent Document 4). (go.jp)
- The purpose of this study is to evaluate whether a concentrate containing both FVIII and von Willebrand Factor (VWF) given at a high dose will induce immune tolerance in subjects who have already experienced and failed ITI with VWF-free FVIII concentrates. (checkorphan.org)
- Both types of concentrates are commonly used to induce immune tolerance in patients with Hemophilia A. Retrospective studies on subjects who were treated with VWF containing Factor VIII concentrates after failing ITI with pure factor VIII concentrates, have shown that tolerance can be achieved in a large percentage of patients. (checkorphan.org)
- This study will access prospectively whether treatment with a FVIII concentrate containing VWF given at a high dose (200 units per kilogram) daily for up to 33 months is able to induce immune tolerance after previous attempts with concentrates containing only FVIII have failed. (checkorphan.org)
- PD-1 (programmed-death 1), an immune-inhibitory receptor required for immune self-tolerance whose deficiency causes autoimmunity with variable severity and tissue specificity depending on other genetic factors, is expressed on activated T cells, including the transcription factor FoxP3(+) Treg cells known to play critical roles in maintaining immune tolerance. (nii.ac.jp)
- Autoimmunity results from a failure or breakdown of the mechanisms normally responsible for maintaining self-tolerance in B cells, T cells, or both. (slideserve.com)
- In this renewal application, we describe the scientific and operational framework that we propose to enable the ITN to successfully accelerate the development of tolerance therapies in transplantation, autoimmunity, and allergy. (grantome.com)
Type 1 Diabet5
- Prior to the onset of type 1 diabetes, there is progressive loss of immune self-tolerance, evidenced by the accumulation of islet autoantibodies and emergence of autoreactive T cells. (diabetesjournals.org)
- Studies of samples from patients with type 1 diabetes and of murine disease models have generated important insights about genetic and environmental factors that contribute to susceptibility and immune pathways that are important for pathogenesis. (diabetesjournals.org)
- Our Epitope-Specific Immuno-Therapy™ (ESIT™) platform provides a precision medicine approach to restoring immune tolerance across a range of diseases, including celiac disease and type 1 diabetes. (globenewswire.com)
- Reestablishing immune tolerance in type 1 diabetes (T1D), a chronic autoimmune disease, is a major goal. (soc-bdr.org)
- Targeted immune interventions for type 1 diabetes: not as easy as it looks! (soc-bdr.org)
- What we are doing is essentially tricking the immune system," into thinking myelin is no longer a threat, said study researcher Stephen Miller, a professor of microbiology and immunology at Northwestern University Feinberg School of Medicine in Chicago. (livescience.com)
- This article briefly traces the early history of the field of tumor immunology with respect to tolerance, and then focuses on a relatively recently identified population of cells called myeloid-derived suppressor cells (MDSCs). (nih.gov)
- The aim of the project is to understand the mechanisms of Egr2 and 3 mediated T cell tolerance in tumour immunology. (findaphd.com)
- Brief report: Autologous stem cell transplantation restores immune tolerance in experimental arthritis by renewal and modulation of the Teff cell compartment. (sigmaaldrich.com)
- PITTSBURGH, November 1, 2000 - Researchers at the University of Pittsburgh's Thomas E. Starzl Transplantation Institute have been awarded $728,000 through the Immune Tolerance Network to study a group of transplant patients who are completely off immunosuppressive drugs to see if clues can yield simple laboratory tests predictive of transplant tolerance, the most elusive goal in the field of transplantation. (upmc.com)
- The Immune Tolerance Network envisions findings of this study to have application to other areas of clinical research, from pancreatic islet transplantation to the treatment of multiple sclerosis. (upmc.com)
- All of the above contribute to the MDSC-related immune tolerance in transplantation. (eurekaselect.com)
- Sykes M. Immune tolerance in recipients of combined haploidentical bone marrow and kidney transplantation. (eurekaselect.com)
- Transplantation is a life-saving intervention for organ failure, but it comes with a significant burden and risk, in each area, pre-clinical studies show that immune tolerance should be an achievable therapeutic prospect for many affected individuals. (grantome.com)
- They are present in most individuals with cancer and because of their potent immune suppressive activity are a major deterrent to natural anti-tumor immunity and a significant obstacle to immunotherapy. (nih.gov)
- The upregulation of IDO1 strongly correlated with increases in other immune checkpoint markers (LAG3 and PD1) and tumor proliferation markers (Ki67), providing targetable immune checkpoint components for drug development and therapy. (cancer.gov)
- This study demonstrates yet another unknown divergence in tumor micro-environments which have implications in patient treatment, providing a rationale for immune checkpoint inhibition in poor outcome ER+ breast cancer. (cancer.gov)
- Such progress helped to better define the cellular, molecular, and epigenetic networks involved in the immune response in the tumor microenvironment and renewed the enthusiasm towards the potential power of cancer immunotherapy. (eurekaselect.com)
- Immune tolerance in cancer mediates tumor escape from the immune system. (global-summit.com)
- Inflammation mediates tumor-induced tolerance. (global-summit.com)
- 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. (pharmatimes.com)
- Medeor Therapeutics is developing a novel cell-based therapy to reprogram the past recipients' immune system to accept the transplanted kidney without the concurrent need for long term use of immunosuppressive drugs. (clinicaltrials.gov)
- We have made significant strides in the discovery and development of immune tolerizing therapeutics that have the potential to transform how we treat patients with autoimmune disorders. (globenewswire.com)
- This is a cornerstone of the Immune Tolerance Network (ITN) approach - clinical assessment of novel tolerance therapeutics, while simultaneously evaluating the cellular, genetic and immunologic mechanisms of disease and how they are altered in response to therapy. (grantome.com)
Antigen-specific immune tolerance3
- Anokion is a biotechnology company that develops products based on proprietary technology for the induction of antigen-specific immune tolerance. (manufacturingchemist.com)
- I am pleased to enter into this agreement with Anokion, under which we will be developing unique and innovative products for antigen-specific immune tolerance,' said Dr Kenji Yasukawa, Senior Vice President and Chief Strategy Officer of Astellas. (manufacturingchemist.com)
- A research collaboration with US-based Janssen Biotech, Inc. supported the translation of the antigen specific immune tolerance induction (ASITI) technology as a treatment for rheumatoid arthritis through to the end of a first-in-human clinical trial. (uniquest.com.au)
- 119-28 ) under the title "Human Her-2 DNA Vaccines Containing Heterologous Rat Neu Sequence Overcome Immune Tolerance to Induce Elevated Antitumor Immunity" was published by mistake in the January 1, 2010 issue of Cancer Research ( 1 ). (aacrjournals.org)
- The coordinated response by the innate immunity and the adaptive immunity is essential for efficient immune response. (aacrjournals.org)
- Many cases of spontaneous abortion may be described in the same way as maternal transplant rejection, and a chronic insufficient tolerance may cause infertility. (wikipedia.org)
- Our study provides a basis for further studies on imDCs in immune tolerance, with the goal of developing effective cellular immunotherapies for transplant recipients. (hindawi.com)
- It is important to understand immune tolerance to grafts in transplant pathology. (hindawi.com)
- The purpose of the current Phase 2 study is to demonstrate the efficacy and safety of MDR-103 for the induction of transplant immune tolerance in a prospective, multicenter clinical trial. (clinicaltrials.gov)
- MDR-103 is intended to induce mixed lymphohematopoietic chimerism and donor specific immune tolerance in order to preserve transplant kidney function, avert transplant kidney rejection, and eliminate the cumulative and serious side effects associated with immunosuppressive drugs. (clinicaltrials.gov)
- The new project will enable further study of these patients, and potentially others, to determine how it is that their transplanted organs continue to be accepted by their immune systems without the aid of drugs, and to identify potential tests that can be predictive of who physicians can wean successfully, tests that may determine and be indicative of transplant tolerance. (upmc.com)
- Treg appear to mainly promote chemotactic and ubiquitin-dependent protein catabolism during transplant rejection while seeming to harness proliferative and immunosuppressive function during tolerance. (biomedcentral.com)
- We also demonstrate that this form of acquired transplant tolerance is associated with increased proliferation and PD-1 expression by Treg. (biomedcentral.com)
- Immune tolerance also does not usually refer to artificially induced immunosuppression by corticosteroids, lymphotoxic chemotherapy agents, sublethal irradiation, etc. (wikipedia.org)
- Among 624 patients receiving transplants between 1977-1997 at Huddinge Hospital, 254 patients surviving more than 12 months, were retrospectively analysed regarding clinical tolerance, that was defined as the absence of GVHD or rejection after withdrawal of immunosuppression. (avhandlingar.se)
Restores immune to1
- An exploratory, open-labeled study of patients with Pompe disease, who have previously received Myozyme (alglucosidase alfa) treatment, to evaluate the efficacy, safety and clinical benefit of 2 Immune Tolerance Induction (ITI) regimens in combination with Myozyme. (clinicaltrials.gov)
- Specifically, the Contractor shall design and conduct clinical trials at all phases to evaluate the safety, toxicity and efficacy of promising tolerance induction strategies in these disease areas, and design and conduct studies of the underlying mechanisms involved in the induction, maintenance and loss of tolerance as an integral part of Network-sponsored clinical trials, as well as clinical trials supported by other Federal and private organizations and companies. (nih.gov)
- Driven by a mission to accelerate the discovery and development of breakthrough treatments for the range of immune-related diseases, the DHMRI provides integrated, state-of-the-art genomic, cellular, proteomic and bioinformatics technology platforms as a major resource for a range of academic and industry partners undertaking both preclinical and clinical research. (bio-medicine.org)
- With the integration of the Immune Tolerance Institute, the Institute is now supporting numerous clinical trials of immunomodulatory therapies and approaches with advanced flow cytometry, immunoassay and gene expression methods across a range of immune-related studies. (bio-medicine.org)
- An innovative immune tolerance technology, the first to target the underlying cause of autoimmune disease rather than treat its inflammatory symptoms, has entered first-in-human clinical trials. (uniquest.com.au)
- In multivariate analysis, a high donor age, donation from an immunised female donor to a male recipient, and acute GVHD grades II-IV were associated with longer time to clinical tolerance. (avhandlingar.se)
- Bringing together microarray data from Alliance/Alliance for Clinical Trials in Oncology neo-adjuvant aromatase inhibitor trials (Z1031), Dr. Ellis and Dr. Zhang examined whether aggressive LumB, endocrine-therapy-resistant tumors were able to progress by developing immune tolerance mechanisms. (cancer.gov)
- The Immune Tolerance Network (ITN) has initiated eight clinical trials of immunomodulatory therapies in recent-onset T1D over the past decade. (soc-bdr.org)
- We also perform genome-wide single-cell RNA-sequencing to interrogate Treg during immune rejection and tolerance and to indicate possible mechanisms involved in sustaining Treg function. (biomedcentral.com)
- We show that Treg are indispensable for tolerance induced by coreceptor and costimulation blockade as depletion of which with an anti-hCD2 antibody resulted in rejection of hESC-derived pancreatic islets in NOD. (biomedcentral.com)
- Our results suggest that short-term coreceptor and costimulation blockade mediates immune tolerance to hESC-derived pancreatic islets by promoting Treg proliferation through engagement of PD-1. (biomedcentral.com)
- Fucoidan could prevent the development of autoimmune diabetes in NOD mice via regulating DC/Treg induced immune tolerance, improving gut microecology, down-regulating TLR4 signaling pathway, and maintaining pancreatic internal environment. (biomedcentral.com)
- During the past 20 years, major advances have been made in understanding the molecular and cellular mechanisms of allergen tolerance in humans. (jci.org)
- The next step, Kahn adds, is to look at Tregs and their role in pregnancy tolerance in humans-a line of research that may lead to new insights into such pregnancy-related conditions as preeclampsia, in which high blood pressure and other symptoms develop in the second half of pregnancy. (scitech-news.com)
- The primary objective of this study is to demonstrate the safety and efficacy of cellular immunotherapy with MDR-103 for induction of functional immune tolerance in past recipients of human leukocyte antigen (HLA)-matched, living donor kidney transplants. (clinicaltrials.gov)
- Allergen immunotherapy, immune therapy safely for allergen starting from a low dose, the dose gradually increased, at this time, the amount of administered allergen exceeds the threshold value can be immediately severe risk of allergy symptoms. (go.jp)
- science, Dr. Matthew Ellis, Co-Principal Investigator of the CPTAC Proteogenomic Translational Research Center and Dr. Bing Zhang, Principal Investigator of the CPTAC Proteogenomic Data Analysis Center, both at Baylor College of Medicine, recently released a study focused on the immune environment of Luminal B (LumB) breast cancer tumors on October 30th, 2019 in the Journal of the National Cancer Institute (advanced version online). (cancer.gov)
- Natural Killer Cell Tolerance: Control by Self or Self-Control? (cshlpress.com)
- The demonstration of T cell tolerance, particularly that mediated by the immune-suppressive functions of IL-10, led to a major conceptual change in this area. (jci.org)
- Short courses of treatment with nonlytic anti-CD4 and anti-CD8 antibodies targeted at both T-cell subsets can induce long-term peripheral T-cell tolerance in primed mice. (nih.gov)
- T cell activation or tolerance has been experimentally induced in TCR-transgenic mice in order to study T cell tolerance both at the cellular and molecular level. (dissertations.se)
- By studying specific intestinal immune cell populations in genetically modified mice, Mortha et al . (sciencemag.org)
- However, Il10(-/-)Rag2(-/-) mice, which lack IL-10 and Tregs, remain healthy, suggesting the existence of other mechanisms of tolerance. (sigmaaldrich.com)
- The purpose of this study is to test the feasibility of neonatal immune tolerance induction in mice to enable long-term pharmacokinetic studies with immunogenic therapeutic monoclonal antibodies (mAb). (springer.com)
- Neonatal immune tolerance was induced by transfer of a mAb to neonatal mice via colostrum from nursing mother mice treated with two subcutaneous doses of a tolerogen starting within the first 24 h after delivery. (springer.com)
- Overall, the present study demonstrated the suitability of neonatal immune tolerance induction for a 4-week single dose study in adult mice with a human therapeutic mAb that is otherwise immunogenic in laboratory animals. (springer.com)
- The immune tolerance to OVA antigen topically applied to the conjunctiva measured by cutaneous delayed type hypersensitivity (DTH) reaction, OVA-specific T cell proliferation, Foxp3 induction, and IFN-γ production observed in WT mice was lost in the Spdef-KO mice. (jci.org)
- Experimental results obtained in the 1990s showed that a short-term CD3 antibody treatment in recently diagnosed diabetic non-obese diabetic (NOD) mice induced permanent remission of the disease by restoring self-tolerance. (soc-bdr.org)
- To check for its involvement in UV-induced tolerance, mice whose CHS were impaired by UV were left untreated for 14 days and then resensitized and rechallenged, resulting that CHS was significantly suppressed as compared to unexposed animals, indicating that tolerance was induced. (nii.ac.jp)
- However, the vaccines failed to elicit immune protection in Δ16HER2 transgenic mice because of tolerogenic mechanisms towards the human HER2 self-antigen, a scenario commonly seen in HER2+ patients. (aacrjournals.org)
- SUMMARY BACKGROUND AND OBJECTIVES: he management of patients with severe hemophilia A and inhibitors to factor VIII (FVIII) resistant to standard immune tolerance is challenging. (nih.gov)
- These data suggest that the use of rituximab combined with FVIII is a potentially useful treatment for patients with inhibitors resistant to standard immune tolerance, although sustained inhibitor eradication is uncommon. (nih.gov)
- The usual treatment of patients with FVIII inhibitors involves what is called "immune tolerance induction" (ITI). (checkorphan.org)
- Background/Purpose: To review the efficiency and tolerance of different proton pump inhibitors (PPIs) in various dosages for sufferers with duodenal ulcers. (immune-source.com)
- One of the leading methods of addressing the development of inhibitors is known as immune tolerance induction, or ITI, therapy. (aspcares.com)
- If immune tolerance therapy is successful, the body stops generating antibodies (inhibitors) and replacement factor concentrates become effective again. (aspcares.com)
- These limitations have sparked investigation into strategies for achieving more specific immune modulation. (frontiersin.org)
- Most pharmaceutical companies were cautious to commit funds to antigen-specific immune tolerising induction therapy, which they considered to still be at an early stage of development. (uniquest.com.au)
Mechanisms of immune1
Establishment of Immune Tolerance1
- Serum pro-inflammatory IL-2, anti-inflammatory IL-4 concentrations and the CD4(+)T/CD8(+)T ratio were measured at 1, 3, 7, 14 and 21 d after surgery to verify the establishment of immune tolerance. (physiciansweekly.com)
- is, processing the natural allergen (component extraction, heat treatment, chemical modifications, such as a sustained release formulation) by, which is capable of inducing immune tolerance while maintaining such allergens, immediate symptoms with reduced risk of inducing the present invention. (go.jp)
- The placenta does not block maternal IgG antibodies, which thereby may pass through the human placenta, providing immune protection to the fetus against infectious diseases. (wikipedia.org)
- The David H. Murdock Research Institute (DHMRI) has acquired the Immune Tolerance Institute (ITI) as part of the North Carolina-based Institute's mission to accelerate the discovery and development of breakthrough treatments for a range of immune-related diseases. (centerwatch.com)
- When tolerance breaks down, severe, self-destructive diseases such as rheumatoid arthritis, lupus, and multiple sclerosis may develop. (cshlpress.com)
- Immune tolerance is critical to prevent the development of autoimmune and inflammatory diseases. (stemcell.com)
- Immune complex - Diseases An immune complex is formed from the integral binding of an antibody to a soluble antigen. (academic.ru)
- The precise events that initiate disease remain unknown, but the most current evidence indicates that antibodies that recognize either insulin or glutamic acid decarboxylase (GAD65) are the earliest evidence of loss of self-tolerance ( 1 , 2 ). (diabetesjournals.org)
- After a single intravenous injection of the same mAb as used for tolerance induction, the pharmacokinetics of the mAb and formation of anti-drug antibodies (ADA) in plasma were assessed using ELISA. (springer.com)