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CD278
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 ... [...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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
T Cell
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell surface. T cells are born from hematopoietic stem cells, found in the bone marrow. Developing T cells then migrate to the thymus gland to develop (or mature). T cells derive their name from the thymus. After migration to the thymus, the precursor cells mature into several distinct types of T cells. T cell differentiation also continues after they have left the thymus. Groups of specific, differentiated T cell subtypes have a variety of important functions in controlling and shaping the immune response. One of these functions is immune-mediated cell death, and it is carried out by two major subtypes: CD8+ "killer" and CD4+ "helper" T cells. (These are named for the presence of the cell surface proteins CD8 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ICOSLG
ICOS ligand (ICOSLG, ICOSL or GL50) is a protein that in humans is encoded by the ''ICOSLG'' gene located at chromosome 21. ICOSLG has also been designated as CD275 (cluster of differentiation 275). ICOSLG is glycosylated transmembrane structure, which is classified as a member of the B7 family due to the significant homology with B7 family members. The B7/CD28 superfamily provides both positive and negative co-signals to immunocytes in immune responses. The interaction of ICOSLG with ICOS, the specific receptor for ICOSLG, is critically involved in the activation, proliferation, differentiation and cytokine production of T cells as well as in the antibody secretion from B cells during secondary immune responses. ICOSLG, which is extensively expressed in both non-lymphatic and lymphatic tissues, is an important molecule in upregulating and promoting T cell immune responses. Expression of ICOSLG in naive B cells and monocytes in PBMCs is at a low level. After stimulation by IFN-γ ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
T Cells
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell surface. T cells are born from hematopoietic stem cells, found in the bone marrow. Developing T cells then migrate to the thymus gland to develop (or mature). T cells derive their name from the thymus. After migration to the thymus, the precursor cells mature into several distinct types of T cells. T cell differentiation also continues after they have left the thymus. Groups of specific, differentiated T cell subtypes have a variety of important functions in controlling and shaping the immune response. One of these functions is immune-mediated cell death, and it is carried out by two major subtypes: CD8+ "killer" and CD4+ "helper" T cells. (These are named for the presence of the cell surface proteins CD8 or ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protein Dimer
In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has roots meaning "two parts", '' di-'' + '' -mer''. A protein dimer is a type of protein quaternary structure. A protein homodimer is formed by two identical proteins. A protein heterodimer is formed by two different proteins. Most protein dimers in biochemistry are not connected by covalent bonds. An example of a non-covalent heterodimer is the enzyme reverse transcriptase, which is composed of two different amino acid chains. An exception is dimers that are linked by disulfide bridges such as the homodimeric protein NEMO. Some proteins contain specialized domains to ensure dimerization (dimerization domains) and specificity. The G protein-coupled cannabinoid receptors have the ability to form both homo- and heterodimers with several ... [...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 environment ... [...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 B ... [...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 n ... [...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, Berkele ... [...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 ... [...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 seve ... [...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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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