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STAT4
Signal transducer and activator of transcription 4 (STAT4) is a transcription factor belonging to the STAT protein family, composed of STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, STAT6. STAT proteins are key activators of gene transcription which bind to DNA in response to cytokine gradient. STAT proteins are a common part of JAK-STAT signaling pathway, Janus kinase (JAK)- signalling pathways, activated by cytokines.STAT4 is required for the development of Th1 cells from naive T helper cell, CD4+ T cells and Interferon-gamma, IFN-γ production in response to Interleukin 12, IL-12. There are two known STAT4 transcripts, STAT4α and STAT4β, differing in the levels of interferon-gamma (IFN-γ )production downstream. Structure Human as well murine STAT4 genes lie next to STAT1 gene locus suggesting that the genes arose by gene duplication. STAT proteins have six functional protein domain, domains: 1. N-terminus, N-terminal interaction domain – crucial for dimerization of inacti ...
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JAK-STAT Signaling Pathway
The JAK-STAT signaling pathway is a chain of interactions between proteins in a cell, and is involved in processes such as immunity, cell division, cell death, and tumor formation. The pathway communicates information from chemical signals outside of a cell to the cell nucleus, resulting in the activation of genes through the process of transcription. There are three key parts of JAK-STAT signalling: Janus kinases (JAKs), signal transducer and activator of transcription proteins (STATs), and receptors (which bind the chemical signals). Disrupted JAK-STAT signalling may lead to a variety of diseases, such as skin conditions, cancers, and disorders affecting the immune system. Structure of JAKs and STATs ''Main articles: JAKs and STATs'' There are four JAK proteins: JAK1, JAK2, JAK3 and TYK2. JAKs contains a FERM domain (approximately 400 residues), an SH2-related domain (approximately 100 residues), a kinase domain (approximately 250 residues) and a pseudokinase domai ...
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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 Immunoglobulin class switching, antibody class switching, breaking Cross-presentation, 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 Receptor (biochemistry), receptors for those cytokines. These cells help polar ...
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Interleukin 12
Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, helper T cells and human B-lymphoblast, lymphoblastoid cells (NC-37) in response to antigenic stimulation. IL-12 belongs to the family of interleukin-12. IL-12 family is unique in comprising the only heterodimeric cytokines, which includes IL-12, Interleukin 23 subunit alpha, IL-23, Interleukin 27, IL-27 and Interleukin 35, IL-35. Despite sharing many structural features and molecular partners, they mediate surprisingly diverse functional effects. Gene and structure IL12 is a heterodimeric cytokine encoded by two separate genes, IL12A, IL-12A (p35) and Interleukin-12 subunit beta, IL-12B (p40). The active heterodimer (referred to as 'p70'), and a homodimer of p40 are formed following protein synthesis. IL12A is composed of a bundle of four alpha helices. IL12B has three beta sheet domains. Functions IL-12 is involved in the differentiation of naive T cells into T ...
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SH2 Domain
The SH2 (Src Homology 2) domain is a structurally conserved protein domain contained within the Src oncoprotein and in many other intracellular signal-transducing proteins. SH2 domains bind to phosphorylated tyrosine residues on other proteins, modifying the function or activity of the SH2-containing protein. The SH2 domain may be considered the prototypical modular protein-protein interaction domain, allowing the transmission of signals controlling a variety of cellular functions. SH2 domains are especially common in adaptor proteins that aid in the signal transduction of receptor tyrosine kinase pathways. Structure and interactions SH2 domains contain about 100 amino acid residues and exhibit a central antiparallel β-sheet centered between two α-helices. Binding to phosphotyrosine-containing peptides involves a strictly-conserved Arg residue that pairs with the negatively-charged phosphate on the phosphotyrosine, and a surrounding pocket that recognizes flanking seque ...
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STAT2
Signal transducer and activator of transcription 2 is a protein that in humans is encoded by the ''STAT2'' gene. It is a member of the STAT protein family. This protein is critical to the biological response of type I interferons (IFNs). It functions as a transcription factor downstream of type I interferons. STAT2 sequence identity between mouse and human is only 68%. Function The protein encoded by this gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. In response to IFN, this protein forms a complex with STAT1 and IFN regulatory factor family protein p48 ( IRF9) and form ISGF-3 (IFN-stimulated gene factor-3), in which this protein acts as a transactivator, but lacks the ability to bind DNA directly. The protein mediates innate antiviral activity. ...
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Negative Feedback
Negative feedback (or balancing feedback) occurs when some function (Mathematics), function of the output of a system, process, or mechanism is feedback, fed back in a manner that tends to reduce the fluctuations in the output, whether caused by changes in the input or by other disturbances. Whereas positive feedback tends to instability via exponential growth, oscillation or chaos theory, chaotic behavior, negative feedback generally promotes stability. Negative feedback tends to promote a settling to List of types of equilibrium, equilibrium, and reduces the effects of perturbations. Negative feedback loops in which just the right amount of correction is applied with optimum timing, can be very stable, accurate, and responsive. Negative feedback is widely used in Mechanical engineering, mechanical and electronic engineering, and it is observed in many other fields including biology, chemistry and economics. General negative feedback systems are studied in Control engin ...
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Natural Killer Cell
Natural killer cells, also known as NK cells, are a type of cytotoxic lymphocyte critical to the innate immune system. They are a kind of large granular lymphocytes (LGL), and belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represent 5–20% of all circulating lymphocytes in humans. The role of NK cells is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. NK cells provide rapid responses to virus-infected cells, stressed cells, tumor cells, and other intracellular pathogens based on signals from several activating and inhibitory receptors. Most immune cells detect the antigen presented on MHC class I, major histocompatibility complex I (MHC-I) on infected cell surfaces, but NK cells can recognize and kill stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction. They were named "natural killers" because of the notion that they do not require activation to kill cells that are m ...
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Interferon Gamma
Interferon gamma (IFNG or IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheelock as a product of human leukocytes stimulated with phytohemagglutinin, and by others as a product of antigen-stimulated lymphocytes. It was also shown to be produced in human lymphocytes. or tuberculin-sensitized mouse peritoneal lymphocytes challenged with Mantoux test (PPD); the resulting supernatants were shown to inhibit growth of vesicular stomatitis virus. Those reports also contained the basic observation underlying the now widely employed interferon gamma release assay used to test for tuberculosis. In humans, the IFNG protein is encoded by the ''IFNG'' gene. Through cell signaling, interferon gamma plays a role in regulating the immune response of its target cell. A key signaling pathway that is activated by ...
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Antigen-presenting Cell
An antigen-presenting cell (APC) or accessory cell is a Cell (biology), cell that displays an antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes using their T cell receptors (TCRs). APCs antigen processing, process antigens and present them to T cells. Almost all cell types can present antigens in some way. They are found in a variety of tissue types. Dedicated antigen-presenting cells, including macrophages, B cells and dendritic cells, present foreign antigens to T helper cell, helper T cells, while virus-infected cells (or cancer cells) can present antigens originating inside the cell to cytotoxic T cells. In addition to the MHC family of proteins, antigen presentation relies on other specialized signaling molecules on the surfaces of both APCs and T cells. Antigen-presenting cells are vital for effective Adaptive immune system, adaptive immune response, as the fun ...
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Atomic Mass Unit
The dalton or unified atomic mass unit (symbols: Da or u, respectively) is a unit of mass defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at rest. It is a non-SI unit accepted for use with SI. The word "unified" emphasizes that the definition was accepted by both IUPAP and IUPAC. The atomic mass constant, denoted , is defined identically. Expressed in terms of , the atomic mass of carbon-12: . Its value in SI units is an experimentally determined quantity. The 2022 CODATA recommended value of the atomic mass constant expressed in the SI base unit kilogram is:This value serves as a conversion factor of mass from daltons to kilograms, which can easily be converted to grams and other metric units of mass. The 2019 revision of the SI redefined the kilogram by fixing the value of the Planck constant (), improving the precision of the atomic mass constant expressed in SI units by anchoring it to fixed physica ...
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B Cell
B cells, also known as B lymphocytes, are a type of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or inserted into the plasma membrane where they serve as a part of B-cell receptors. When a naïve or memory B cell is activated by an antigen, it proliferates and differentiates into an antibody-secreting effector cell, known as a plasmablast or plasma cell. In addition, B cells Antigen presentation, present antigens (they are also classified as professional Antigen-presenting cell, antigen-presenting cells, APCs) and secrete cytokines. In mammals B cells Cellular differentiation, mature in the bone marrow, which is at the core of most bones. In birds, B cells mature in the bursa of Fabricius, a lymphoid organ where they were first discovered by Chang and Glick, which is why the ''B'' stands for ''bursa'' and not ''bone marrow'', as commonly believed. B cells, unl ...
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Promoter (genetics)
In genetics, a promoter is a sequence of DNA to which proteins bind to initiate transcription of a single RNA transcript from the DNA downstream of the promoter. The RNA transcript may encode a protein (mRNA), or can have a function in and of itself, such as tRNA or rRNA. Promoters are located near the transcription start sites of genes, upstream on the DNA (towards the 5' region of the sense strand). Promoters can be about 100–1000 base pairs long, the sequence of which is highly dependent on the gene and product of transcription, type or class of RNA polymerase recruited to the site, and species of organism. Overview For transcription to take place, the enzyme that synthesizes RNA, known as RNA polymerase, must attach to the DNA near a gene. Promoters contain specific DNA sequences such as response elements that provide a secure initial binding site for RNA polymerase and for proteins called transcription factors that recruit RNA polymerase. These transcription factor ...
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