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Central Tolerance
In immunology, central tolerance (also known as negative selection) is the process of eliminating any ''developing'' T or B lymphocytes that are autoreactive, i.e. reactive to the body itself. Through elimination of autoreactive lymphocytes, tolerance ensures that the immune system does not attack self peptides. Lymphocyte maturation (and central tolerance) occurs in primary lymphoid organs such as the bone marrow and the thymus. In mammals, B cells mature in the bone marrow and T cells mature in the thymus. Central tolerance is not perfect, so peripheral tolerance exists as a secondary mechanism to ensure that T and B cells are not self-reactive once they leave primary lymphoid organs. Peripheral tolerance is distinct from central tolerance in that it occurs once developing immune cells exit primary lymphoid organs (the thymus and bone-marrow), prior to their export into the periphery. Function of central tolerance Central tolerance is essential to proper immune cell functi ...
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Immunology
Immunology is a branch of medicineImmunology for Medical Students, Roderick Nairn, Matthew Helbert, Mosby, 2007 and biology that covers the medical study of immune systems in humans, animals, plants and sapient species. In such we can see there is a difference of human immunology and comparative immunology in veterinary medicine and animal biosciences. Immunology measures, uses charts and differentiate in context in medicine the studies of immunity on cell and molecular level, and the immune system as part of the physiological level as its functioning is of major importance. In the different states of both health, occurring symptoms and diseases; the functioning of the immune system and immunological responses such as autoimmune diseases, allergic hypersensitivities, or in some cases malfunctioning of immune system as for example in immunological disorders or in immune deficiency, and the specific transplant rejection) Immunology has applications in numerous disciplines of ...
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Receptor Editing
Receptor editing is a process that occurs during the maturation of B cells, which are part of the adaptive immune system. This process forms part of central tolerance to attempt to change the specificity of the antigen receptor of self reactive immature B-cells, in order to rescue them from programmed cell death, called apoptosis. It is thought that 20-50% of all peripheral naive B cells have undergone receptor editing making it the most common method of removing self reactive B cells. During maturation in the bone marrow, B cells are tested for interaction with self antigens, which is called negative selection. If the maturing B cells strongly interact with these self antigens, they undergo death by apoptosis. Negative selection is important to avoid the production of B cells that could cause autoimmune diseases An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, ...
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Legend For T Cell Selection Figures
A legend is a genre of folklore that consists of a narrative featuring human actions, believed or perceived, both by teller and listeners, to have taken place in human history. Narratives in this genre may demonstrate human values, and possess certain qualities that give the tale verisimilitude. Legend, for its active and passive participants may include miracles. Legends may be transformed over time to keep them fresh and vital. Many legends operate within the realm of uncertainty, never being entirely believed by the participants, but also never being resolutely doubted. Legends are sometimes distinguished from myths in that they concern human beings as the main characters rather than gods, and sometimes in that they have some sort of historical basis whereas myths generally do not. The Brothers Grimm defined ''legend'' as "folktale historically grounded". A by-product of the "concern with human beings" is the long list of legendary creatures, leaving no "resolute doubt" tha ...
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FOXP3
FOXP3 (forkhead box P3), also known as scurfin, is a protein involved in immune system responses. A member of the FOX protein family, FOXP3 appears to function as a master regulator of the regulatory pathway in the development and function of regulatory T cells. Regulatory T cells generally turn the immune response down. In cancer, an excess of regulatory T cell activity can prevent the immune system from destroying cancer cells. In autoimmune disease, a deficiency of regulatory T cell activity can allow other autoimmune cells to attack the body's own tissues. While the precise control mechanism has not yet been established, FOX proteins belong to the forkhead/winged-helix family of transcriptional regulators and are presumed to exert control via similar DNA binding interactions during transcription. In regulatory T cell model systems, the FOXP3 transcription factor occupies the promoters for genes involved in regulatory T-cell function, and may inhibit transcription of key gene ...
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Regulatory T Cell
The regulatory T cells (Tregs or Treg cells), formerly known as suppressor T cells, are a subpopulation of T cells that modulate the immune system, maintain tolerance to self-antigens, and prevent autoimmune disease. Treg cells are immunosuppressive and generally suppress or downregulate induction and proliferation of effector T cells. Treg cells express the biomarkers CD4, FOXP3, and CD25 and are thought to be derived from the same lineage as naïve CD4+ cells. Because effector T cells also express CD4 and CD25, Treg cells are very difficult to effectively discern from effector CD4+, making them difficult to study. Research has found that the cytokine transforming growth factor beta (TGF-β) is essential for Treg cells to differentiate from naïve CD4+ cells and is important in maintaining Treg cell homeostasis. Mouse models have suggested that modulation of Treg cells can treat autoimmune disease and cancer and can facilitate orga ...
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FEZF1
FEZ family zinc finger 1 is a protein that in humans is encoded by the FEZF1 gene. Clinical significance FEZF1 is a gene that encodes for transcriptional repressors, and it has been shown to repress the transcription factor HES5. In the mouse, FEZF1 is expressed in the forebrain in early development of the embryo. This suppression of HES5 helps to control the differentiation of neural stem cells. FEZF1 also helps to divide the caudal forebrain into three distinct parts during development: the prethalamus, the thalamus, and the pretectum. Mice lacking FEZF1 had no prethalamus and had a smaller thalamus. A loss of function mutation in FEZF1 causes Kallmann Syndrome. As axons are developing and migrating in the early embryo, FEZF1 allows the axons of olfactory neurons to attach to the central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the re ...
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Autoimmune Regulator
The autoimmune regulator (''AIRE'') is a protein that in humans is encoded by the ''AIRE'' gene. It is a 13kb gene on chromosome 21q22.3 that has 545 amino acids. AIRE is a transcription factor expressed in the medulla (inner part) of the thymus. It is part of the mechanism which eliminates self-reactive T cells that would cause autoimmune disease. It exposes T cells to normal, healthy proteins from all parts of the body, and T cells that react to those proteins are destroyed. Each T cell recognizes a specific antigen when it is presented in complex with a major histocompatibility complex (MHC) molecule by an antigen presenting cell. This recognition is accomplished by the T cell receptors expressed on the cell surface. T cells receptors are generated by randomly shuffled gene segments which results in a highly diverse population of T cells - each with a unique antigen specificity. Subsequently, T cells with receptors that recognize the body's own proteins need to be eliminat ...
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T Cell Negative Selection
T, or t, is the twentieth letter in the Latin alphabet, used in the modern English alphabet, the alphabets of other western European languages and others worldwide. Its name in English is ''tee'' (pronounced ), plural ''tees''. It is derived from the Semitic Taw 𐤕 of the Phoenician alphabet, Phoenician and Paleo-Hebrew script (Aramaic alphabet, Aramaic and Hebrew alphabet, Hebrew Taw ת/𐡕/, Syriac alphabet, Syriac Taw ܬ, and Arabic script, Arabic ت Tāʼ) via the Greek letter tau, τ (tau). In English, it is most commonly used to represent the voiceless alveolar plosive, a sound it also denotes in the International Phonetic Alphabet. It is the most commonly used consonant and the second most commonly used letter in English-language texts. History ''Taw'' was the last letter of the Western Semitic alphabets, Semitic and Hebrew alphabets. The sound value of Semitic ''Taw'', Greek alphabet Tαυ (''Tau''), Old Italic alphabet, Old Italic and Latin T has remained fair ...
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T Helper Cell
The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considered essential in B cell antibody class switching, breaking cross-tolerance in dendritic cells, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages and neutrophils. CD4+ cells are mature Th cells that express the surface protein CD4. Genetic variation in regulatory elements expressed by CD4+ cells determines susceptibility to a broad class of autoimmune diseases. Structure and function Th cells contain and release cytokines to aid other immune cells. Cytokines are small protein mediators that alter the behavior of target cells that express receptors for those cytokines. These cells help polarize the immune response depending on the nature of the immunological insult ...
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Cytotoxic T Cell
A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pathogens (such as viruses or bacteria), or cells that are damaged in other ways. Most cytotoxic T cells express T-cell receptors (TCRs) that can recognize a specific antigen. An antigen is a molecule capable of stimulating an immune response and is often produced by cancer cells, viruses, bacteria or intracellular signals. Antigens inside a cell are bound to class I MHC molecules, and brought to the surface of the cell by the class I MHC molecule, where they can be recognized by the T cell. If the TCR is specific for that antigen, it binds to the complex of the class I MHC molecule and the antigen, and the T cell destroys the cell. In order for the TCR to bind to the class I MHC molecule, the former must be accompanied by a glycoprotein ...
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MHC Class II
MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on professional antigen-presenting cells such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial cells, and B cells. These cells are important in initiating immune responses. The antigens presented by class II peptides are derived from extracellular proteins (not cytosolic as in MHC class I). Loading of a MHC class II molecule occurs by phagocytosis; extracellular proteins are endocytosed, digested in lysosomes, and the resulting epitopic peptide fragments are loaded onto MHC class II molecules prior to their migration to the cell surface. In humans, the MHC class II protein complex is encoded by the human leukocyte antigen gene complex (HLA). HLAs corresponding to MHC class II are HLA-DP, HLA-DM, HLA-DOA, HLA-DOB, HLA-DQ, and HLA-DR. Mutations in the HLA gene complex can lead to bare lymphocyte syndrome (BLS), which is a type of MHC ...
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MHC Class I
MHC class I molecules are one of two primary classes of major histocompatibility complex (MHC) molecules (the other being MHC class II) and are found on the cell surface of all nucleated cells in the bodies of vertebrates. They also occur on platelets, but not on red blood cells. Their function is to display peptide fragments of proteins from within the cell to cytotoxic T cells; this will trigger an immediate response from the immune system against a particular non-self antigen displayed with the help of an MHC class I protein. Because MHC class I molecules present peptides derived from cytosolic proteins, the pathway of MHC class I presentation is often called ''cytosolic'' or ''endogenous pathway''. In humans, the HLAs corresponding to MHC class I are HLA-A, HLA-B, and HLA-C. Function Class I MHC molecules bind peptides generated mainly from degradation of cytosolic proteins by the proteasome. The MHC I:peptide complex is then inserted via endoplasmic reticulum into the ext ...
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