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major food fish of Arctic and cold-temperate waters (同)codfish
lean white flesh of important North Atlantic food fish; usually baked or poached (同)codfish
lettuce with long dark-green leaves in a loosely packed elongated head (同)cos_lettuce, romaine, romaine lettuce

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cosine
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cobaltの化学記号

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/11/11 20:06:41」(JST)

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During the activation of lymphocytes, co-stimulation is often crucial to the development of an effective immune response. Co-stimulation is required in addition to the antigen-specific signal from their antigen receptors.^[1]

T Cell Co-stimulation

T cells require two signals to become fully activated. A first signal, which is antigen-specific, is provided through the T cell receptor which interacts with peptide-MHC molecules on the membrane of antigen presenting cells (APC). A second signal, the co-stimulatory signal, is antigen nonspecific and is provided by the interaction between co-stimulatory molecules expressed on the membrane of APC and the T cell.

One of the best characterized costimulatory molecules expressed by T cells is CD28, which interacts with CD80 (B7.1) and CD86 (B7.2) on the membrane of APC. Another costimulatory receptor expressed by T cells is ICOS ( Inducible Costimulator), which interacts with ICOS-L.

T cell co-stimulation is necessary for T cell proliferation, differentiation and survival. Activation of T cells without co-stimulation may lead to T cell anergy, T cell deletion or the development of immune tolerance.

B Cell Co-stimulation

B cell binds antigens with its BCR (a membrane-bound antibody), which transfers intracellular signals to the B cell as well as inducing the B cell to engulf the antigen, process it, and present it on the MHC II molecules. The latter case induces recognition by antigen-specific Th2 cells, leading to activation of the B cell through binding of TCR to the MHC-antigen complex. It is followed by synthesis and presentation of CD40L (CD154) on the Th2 cell, which binds to CD40 on the B cell, thus the Th2 cell can co-stimulate the B cell.^[1] Without this co-stimulation the B cell cannot proliferate further. ^[2]

Co-stimulation for B cells is provided alternatively by complement receptors. Microbes may activate the complement system directly and complement component C3b bind to microbes. After C3b is degraded into a fragment iC3b (inactive derivative of C3b), then cleaved to C3dg, and finally to C3d, which continue to bind to microbal surface, B cells express complement receptor CR2 (CD21) to bind to iC3b, C3dg, or C3d.^[3] This additional binding makes the B cells 100- to 10,000-fold more sensitive to antigen.^[4] CR2 on mature B cells forms a complex with CD19 and CD81. This complex is called the B cell coreceptor complex for such sensitivity enhancement to the antigen.^[5]

Applications

Abatacept (Orencia) is a T cell co-stimulation modulator approved for the treatment of rheumatoid arthritis. The cytokines secreted by activated T cells are thought to both initiate and propagate the immunologically driven inflammation associated with rheumatoid arthritis. Orencia, a soluble fusion protein, works by altering the co-stimulatory signal required for full T-cell activation. Belatacept is another novel molecule which is being tested for use in renal transplantation.

A new co-stimulatory superagonistic drug, TGN1412, was the subject of a clinical trial at Northwick Park Hospital, London. The trial became surrounded in controversy as the six volunteers became seriously ill within minutes of being given the drug.

In essence, the co-stimulatory molecules function as "flashing red lights" that interact with the T cell, communicating that the material being presented by the dendritic cell material indicates danger. Dendritic cells displaying co-stimulatory molecules while presenting antigen are able to activate T cells. In contrast, T cells that recognize antigen presented by a dendritic cell not displaying co-stimulatory molecules are generally driven to apoptosis, or may become unresponsive to future encounters with the antigen.

References

^ ^a ^b Janeway CA, Travers P, Walport M, Shlomchik M (2001). Immunobiology 5 : The Immune System in Health and Disease, 5th ed. New York: Garland Pub., ISBN 0-8153-3642-X
^ Noelle, R. J.; Roy, M.; Shepherd, D. M.; Stamenkovic, I.; Ledbetter, J. A.; Aruffo, A. (1992). "A 39-kDa protein on activated helper T cells binds CD40 and transduces the signal for cognate activation of B cells". Proceedings of the National Academy of Sciences of the United States of America 89 (14): 6550–6554. doi:10.1073/pnas.89.14.6550. PMC 49539. PMID 1378631.
^ Frank K, Atkinson JP (2001). "Complement system." In Austen KF, Frank K, Atkinson JP, Cantor H. eds. Samter's Immunologic Diseases, 6th ed. Vol. 1, p. 281–298, Philadelphia: Lippincott Williams & Wilkins, ISBN 0-7817-2120-2
^ Dempsey, P. W.; Allison, M. E.; Akkaraju, S.; Goodnow, C. C.; Fearon, D. T. (1996). "C3d of complement as a molecular adjuvant: Bridging innate and acquired immunity". Science 271 (5247): 348–350. doi:10.1126/science.271.5247.348. PMID 8553069.
^ Abbas AK, Lichtman AH (2003). Cellular and Molecular Immunology, 5th ed. Philadelphia: Saunders, ISBN 0-7216-0008-5.

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English Journal

Therapeutic human monoclonal antibodies in inflammatory diseases.

Kotsovilis S, Andreakos E.SourceLaboratory of Immunogenetics, Center of Immunology and Transplantation, Immunobiology Division, Biomedical Research Foundation of the Academy of Athens, Athens, Hellas, Greece.
Methods in molecular biology (Clifton, N.J.).Methods Mol Biol.2014;1060:37-59. doi: 10.1007/978-1-62703-586-6_3.
Monoclonal antibodies (mAbs) are antibodies of a single antigen specificity produced by identical immune cells, i.e., clones of a common germ cell. They offer unprecedented opportunities to drug development because of their ability to target almost any cell surface or secreted molecule with remarkab
PMID 24037835

CD80 (B7.1) and CD86 (B7.2) induce EBV-transformed B cell apoptosis through the Fas/FasL pathway.

Park GB, Kim YS, Lee HK, Cho DH, Kim D, Hur DY.SourceDepartment of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Busan 614-735, Republic of Korea.
International journal of oncology.Int J Oncol.2013 Nov;43(5):1531-40. doi: 10.3892/ijo.2013.2091. Epub 2013 Sep 5.
CD80 and CD86 expression is strongly regulated in B cells and is induced by various stimuli (e.g., cytokines, ligation of MHC class II and CD40 ligand). Epstein-Barr virus (EBV) infection activates B lymphocytes and transforms them into lymphoblastoid cells. However, the role of CD80 and CD86 in E
PMID 24008628

Role of drug-independent stress factors in liver injury associated with diclofenac intake.

Ramm S, Mally A.SourceDepartment of Toxicology, University of Würzburg, Germany.
Toxicology.Toxicology.2013 Oct 4;312C:83-96. doi: 10.1016/j.tox.2013.08.002. Epub 2013 Aug 9.
Although a basic understanding of the chemical and biological events leading to idiosyncratic drug toxicity is still lacking, it appears that drug-independent risk factors that increase reactive metabolite formation or alter cellular stress and immune response may be critical determinants in the res
PMID 23939143

Japanese Journal

A caspase 8-based suicide switch induces apoptosis in nanobody-directed chimeric receptor expressing T cells

KHALEGHI Sepideh,RAHBARIZADEH Fatemeh,AHMADVAND Davoud,RASAEE Mohammad J.,POGNONEC Philippe
International journal of hematology 95(4), 434-444, 2012-04-01
NAID 10030632692

Extracts of Larix Leptolepis effectively augments the generation of tumor antigen-specific cytotoxic T lymphocytes via activation of dendritic cells in TLR-2 and TLR-4-dependent manner

Koizumi Shin-ichi,Masuko Kazutaka,Wakita Daiko,Tanaka Sachi,Mitamura Rieko,Kato Yoshihiro,Tabata Homare,Nakahara Masahiro,Kitamura Hidemitsu,Nishimura Takashi
Cellular Immunology 276(1-2), 153-161, 2012-03
… ELL induced production of Type-1 cytokines such as IL-12 and TNF-α from bone marrow-derived dendritic cells (BMDCs) in TLR2- and TLR4-dependent manner and remarkably up-regulated the expression of MHC and co-stimulatory molecules. …
NAID 120004710972

解糖系酵素に対する自己免疫応答と関節リウマチ

松本功,岩波慶一,田中陽子,井上明日香,田中勇希,梅田直人,住田孝之
日本臨床免疫学会会誌 = Japanese journal of clinical immunology 34(6), 456-463, 2011-12-31
関節リウマチ（rheumatoid arthritis : RA）においては，TNFαやIL-6及びT細胞共刺激分子をターゲットにした生物学的製剤の有効性が証明され，これら分子の重要性が再認識されている．また欧米においては，B細胞表面抗原に対する抗体である抗CD20抗体がRAにも第二選択の生物学的製剤として使用され，強い有効性が実証されている．RA診断においては，リウマトイ …
NAID 10030465112

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