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Inducible T-cell Costimulator
Inducible T-cell costimulator is an immune checkpoint protein that in humans is encoded by the ''ICOS'' gene. CD278 or ICOS (Inducible T-cell COStimulator) is a CD28-superfamily costimulatory molecule that is expressed on activated T cells. It is thought to be important for Th2 cells in particular. Function The protein encoded by this gene belongs to the CD28 and CTLA-4 cell-surface receptor family. It forms homodimers and plays an important role in cell-cell signaling, immune responses and regulation of cell proliferation. Knockout phenotype Compared to wild-type naïve T cells, ICOS-/- T cells activated with plate-bound anti- CD3 have reduced proliferation and IL-2 secretion. The defect in proliferation can be rescued by addition of IL-2 to the culture, suggesting the proliferative defect is due either to ICOS-mediated IL-2 secretion or the activation of similar signaling pathways between ICOS and IL-2. In terms of Th1 and Th2 cytokine secretion, ICOS-/- CD4+ T cell a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Immune Checkpoint
Immune checkpoints are regulators of the immune system. These pathways are crucial for self-tolerance, which prevents the immune system from attacking cells indiscriminately. However, some cancers can protect themselves from attack by stimulating immune checkpoint targets. Inhibitory checkpoint molecules are targets for cancer immunotherapy due to their potential for use in multiple types of cancers. Currently approved checkpoint inhibitors block CTLA4 and PD-1 and PD-L1. For the related basic science discoveries, James P. Allison and Tasuku Honjo won the Tang Prize in Biopharmaceutical Science and the Nobel Prize in Physiology or Medicine in 2018. Stimulatory checkpoint molecules Four stimulatory checkpoint molecules are members of the tumor necrosis factor (TNF) receptor superfamily—CD27, CD40, OX40, GITR and CD137. Another two stimulatory checkpoint molecules belong to the B7-CD28 superfamily—CD28 itself and ICOS. * CD27: This molecule supports antigen-specific ex ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
IFN-g
Interferon gamma (IFN-γ) is a protein dimer, 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, IFN-γ release assay used to test for tuberculosis. In humans, the IFN-γ protein is encoded by the ''IFNG'' gene. Through cell signaling, IFN-γ plays a role in regulating the immune response of its target cell. A key signaling pathway that is a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ligand
In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electron pairs, often through Lewis bases. The nature of metal–ligand bonding can range from covalent to ionic. Furthermore, the metal–ligand bond order can range from one to three. Ligands are viewed as Lewis bases, although rare cases are known to involve Lewis acidic "ligands". Metals and metalloids are bound to ligands in almost all circumstances, although gaseous "naked" metal ions can be generated in a high vacuum. Ligands in a complex dictate the reactivity of the central atom, including ligand substitution rates, the reactivity of the ligands themselves, and redox. Ligand selection requires critical consideration in many practical areas, including bioinorganic and medicinal chemistry, homogeneous catalysis, and environmental chemi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
C57BL/6
C57BL/6, often referred to as "C57 black 6", "C57" or "black 6", is a common inbred strain of laboratory mouse. It is the most widely used "genetic background" for genetically modified mice for use as models of human disease. They are the most widely used and best-selling mouse strain, due to the availability of congenic strains, easy breeding, and robustness. Origin The inbred strain of C57BL mice was created in 1921 by C. C. Little at the Bussey Institute for Research in Applied Biology. The substrain "6" was the most popular of the surviving substrains. Little's supervisor William E. Castle had obtained the predecessor strain of C57BL/6, "mouse number 57", from Abbie Lathrop who was breeding inbred strains for mammary tumor research in collaboration with Leo Loeb at the time. Appearance and behavior C57BL/6 mice have a dark brown, nearly black coat. They are more sensitive to noise and odours and are more likely to bite than the more docile laboratory strains such as BA ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CTLA-4
CTLA-4 or CTLA4 (cytotoxic T-lymphocyte-associated protein 4), also known as CD152 (cluster of differentiation 152), is a protein receptor that functions as an immune checkpoint and downregulates immune responses. CTLA-4 is constitutively expressed in regulatory T cells but only upregulated in conventional T cells after activation – a phenomenon which is particularly notable in cancers. It acts as an "off" switch when bound to CD80 or CD86 on the surface of antigen-presenting cells. The CTLA-4 protein is encoded by the ''Ctla-4'' gene in mice and the ''CTLA-4'' gene in humans. History CTLA-4 was first identified in 1991 as a second receptor for the T cell costimulation ligand B7. In November 1995, the labs of Tak Wah Mak and Arlene H. Sharpe independently published their findings on the discovery of the function of CTLA-4 as a negative regulator of T-cell activation, by knocking out the gene in mice. Previous studies from several labs had used methods which could not def ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ipilimumab
Ipilimumab, sold under the brand name Yervoy, is a monoclonal antibody medication that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system. Cytotoxic T lymphocytes (CTLs) can recognize and destroy cancer cells. However, an inhibitory mechanism interrupts this destruction. Ipilimumab turns off this inhibitory mechanism and boosts the body's immune response against cancer cells. Ipilimumab was approved by the US Food and Drug Administration (FDA) in March 2011, for the treatment of melanoma, a type of skin cancer. It is undergoing clinical trials for the treatment of non-small cell lung carcinoma (NSCLC), small cell lung cancer (SCLC), (completed) bladder cancer (completed) and metastatic hormone-refractory prostate cancer. The concept of using anti-CTLA4 antibodies to treat cancer was first developed by James P. Allison while he was director of the Cancer Research Laboratory at the University of California, Berkeley. Cl ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
IgG1
Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG antibody has two paratopes. Function Antibodies are major components of humoral immunity. IgG is the main type of antibody found in blood and extracellular fluid, allowing it to control infection of body tissues. By binding many kinds of pathogens such as viruses, bacteria, and fungi, IgG protects the body from infection. It does this through several mechanisms: * IgG-mediated binding of pathogens causes their immobilization and binding together via agglutination; IgG coating of pathogen surfaces (known as opsonization) allows their recognition and ingestion by phagocytic immune cells leading to the elimination of the pathogen itself; * IgG activates all the classical pathway of the complement system, a cascade of immune protein pr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Interleukin 5
Interleukin 5 (IL5) is an interleukin produced by type-2 T helper cells and mast cells. Function Through binding to the interleukin-5 receptor, interleukin 5 stimulates B cell growth and increases immunoglobulin secretion - primarily IgA. It is also a key mediator in eosinophil activation. Structure IL-5 is a 115-amino acid (in human, 133 in the mouse) -long TH2 cytokine that is part of the hematopoietic family. Unlike other members of this cytokine family (namely interleukin 3 and GM-CSF), this glycoprotein in its active form is a homodimer. Tissue expression The IL-5 gene is located on chromosome 11 in the mouse, and chromosome 5 in humans, in close proximity to the genes encoding IL-3, IL-4, and granulocyte-macrophage colony-stimulating factor (GM-CSF), which are often co-expressed in TH2 cells. Interleukin-5 is also expressed by eosinophils and has been observed in the mast cells of asthmatic airways by immunohistochemistry. IL-5 expression is regulated by several ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Freund's Adjuvant
Freund's adjuvant is a solution of antigen emulsified in mineral oil and used as an immunopotentiator (booster). The complete form, Freund's Complete Adjuvant (FCA or CFA) is composed of inactivated and dried mycobacteria (usually '' M. tuberculosis''), whereas the incomplete form (FIA or IFA) lacks the mycobacterial components (hence just the water in oil emulsion). It is named after Jules T. Freund. Regulation Freund's complete adjuvant is effective in stimulating cell-mediated immunity and leads to potentiation of T helper cells that leads to the production of certain immunoglobulins and effector T cells. Its use in humans is forbidden by regulatory authorities, due to its toxicity. Even for animal research there are currently guidelines associated with its use, due to its painful reaction and potential for tissue damage. Injections of FCA should be subcutaneous or intraperitoneal, because intradermal injections may cause skin ulceration and necrosis; intramuscular injections m ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Alum
An alum () is a type of chemical compound, usually a hydrated double salt, double sulfate salt (chemistry), salt of aluminium with the general chemical formula, formula , where is a valence (chemistry), monovalent cation such as potassium or ammonium. By itself, "alum" often refers to potassium alum, with the formula . Other alums are named after the monovalent ion, such as sodium alum and ammonium alum. The name "alum" is also used, more generally, for salts with the same formula and structure, except that aluminium is replaced by another valence (chemistry), trivalent metal ion like chromium#Chromium(III), chromium, and/or sulfur is replaced by another chalcogen like selenium. The most common of these analogs is chrome alum . In most industries, the name "alum" (or "papermaker's alum") is used to refer to aluminium sulfate, , which is used for most industrial flocculation (the variable is an integer whose size depends on the amount of water absorbed into the alum). In medic ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Keyhole Limpet Hemocyanin
Keyhole limpet hemocyanin (KLH) is a large, multisubunit, oxygen-carrying, metalloprotein that is found in the hemolymph of the giant keyhole limpet, ''Megathura crenulata'', a species of keyhole limpet that lives off the coast of California, from Monterey Bay to Isla Asuncion off Baja California. Protein properties There are two keyhole limpet hemocyanin genes, termed KLH1 and KLH2 which share around 60% identity at the protein level. Both encode large glycosylated proteins consisting of around 3400 amino acids and a molecular weight of around 390,000 Daltons, excluding the glycosylation. The protein oligomerises to form a barrel shaped didecameric complex which is composed of 20 monomers. Each domain of a KLH subunit contains two copper atoms that together bind a single oxygen molecule (O2). When oxygen is bound to hemocyanin, the molecule takes on a distinctive transparent, opalescent blue color, due to the Cu2+ state of the copper. In the absence of oxygen, the bound copper ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Interleukin 4
The interleukin 4 (IL4, IL-4) is a cytokine that induces differentiation of naive helper T cells ( Th0 cells) to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4 in a positive feedback loop. IL-4 is produced primarily by mast cells, Th2 cells, eosinophils and basophils. It is closely related and has functions similar to IL-13. Function Interleukin 4 has many biological roles, including the stimulation of activated B cell and T cell proliferation, and the differentiation of B cells into plasma cells. It is a key regulator in humoral and adaptive immunity. IL-4 induces B cell class switching to IgE, and up-regulates MHC class II production. IL-4 decreases the production of Th1 cells, macrophages, IFNγ, and dendritic cells IL-12. Overproduction of IL-4 is associated with allergies. * Inflammation and wound repair Tissue macrophages play an important role in chronic inflammation and wound repair. Th ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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