Immunology_Janeway

Immunology_Janeway. sipuleucel-T (Provenge) Cell-based immunotherapy used to treat prostate cancer that combined prostatic acid phosphatase as a tumor rejection antigen presented by dendritic cells derived from a patient's monocytes. sirolimus See rapamycin. Sjögren’s syndrome An autoimmune disease in which exocrine glands, particularly the lacrimal glands of the eyes and salivary glands of the mouth, are damaged by the immune system. This results in dry eyes and mouth. Skint-1 A transmembrane immunoglobulin superfamily member expressed by thymic stromal cells and keratinocytes that is required for the development of dendritic epidermal T cells, which are a type of γ:δ T cell. SLAM (signaling lymphocyte activation molecule) A family of related cell-surface receptors that mediate adhesion between lymphocytes, that includes SLAM, 2B4, CD84, Ly106, Ly9, and CRACC. slings See shear-resistant rolling.


Immunology_Janeway

Immunology_Janeway. slings See shear-resistant rolling. SLP-65 A scaffold protein in B cells that recruits proteins involved in the intracellular signaling pathway from the antigen receptor. Also called BLNK. SLP-76 A scaffold protein involved in the antigen-receptor signaling pathway in lymphocytes. small G proteins Single-subunit G proteins, such as Ras, that act as intracellular signaling molecules downstream of many transmembrane signaling events. Also called small GTPases. small pre-B cell Stage in B-cell development immediately after the large pre-B cell in which cell proliferation ceases and light-chain gene rearrangement commences. somatic diversification theories Gerenal hypotheses proposing that the immunoglobulin repertoire was formed from a small number of V genes that diversified in somatic cells. Cf. germline theory.


Immunology_Janeway

Immunology_Janeway. somatic diversification theories Gerenal hypotheses proposing that the immunoglobulin repertoire was formed from a small number of V genes that diversified in somatic cells. Cf. germline theory. somatic DNA recombination DNA recombination that takes place in somatic cells (to distinguish it from the recombination that takes place during meiosis and gamete formation). somatic gene therapy The introduction of functional genes into somatic cells to treat disease. somatic hypermutation Mutations in V-region DNA of rearranged immunoglobulin genes that produce variant immunoglobulins, some of which bind antigen with a higher affinity. These mutations affect only somatic cells and are not inherited through germline transmission. spacer See 12/23 rule. sphingolipids A class of membrane lipid containing sphingosine (2-amino4-octadecene-1,3-diole), an amino alcohol with unsaturated 18-hydrocarbon chain.


Immunology_Janeway

Immunology_Janeway. spacer See 12/23 rule. sphingolipids A class of membrane lipid containing sphingosine (2-amino4-octadecene-1,3-diole), an amino alcohol with unsaturated 18-hydrocarbon chain. sphingosine 1-phosphate (S1P) A phospholipid with chemotactic activity that controls the egress of T cells from lymph nodes. sphingosine 1-phosphate receptor (S1P1) A G-protein-coupled receptor activated by sphingosine 1-phosphate, a lipid mediator in the blood that regulates several physiologic processes, including the trafficking of naive lymphocytes from tissues into the blood. spleen An organ in the upper left side of the peritoneal cavity containing a red pulp, involved in removing senescent blood cells, and a white pulp of lymphoid cells that respond to antigens delivered to the spleen by the blood. S-protein (vitronectin) Plasma protein that binds incompletely formed MAC complexes, such as C5b67, preventing bystander complement damage to host membranes.


Immunology_Janeway

Immunology_Janeway. S-protein (vitronectin) Plasma protein that binds incompletely formed MAC complexes, such as C5b67, preventing bystander complement damage to host membranes. Spt5 A transcription elongation factor required for isotype switching in B cells that functions in associatioin with RNA polymerase to enable recruitment of AID to its targets in the genome. SR-A I, SR-A II See scavenger receptors. Src-family protein tyrosine kinases Receptor-associated protein tyrosine kinases characterized by Src-homology protein domains (SH1, SH2, and SH3). The SH1 domain contains the kinase, the SH2 domain can bind phosphotyrosine residues, and the SH3 domain can interact with proline-rich regions in other proteins. In T cells and B cells they are involved in relaying signals from the antigen receptor. staphylococcal complement inhibitor (SCIN) Staphylococcal protein that inhibits the activity of the classical and alternative C3 convertases, promoting the evasion of destruction by complement.


Immunology_Janeway

Immunology_Janeway. staphylococcal complement inhibitor (SCIN) Staphylococcal protein that inhibits the activity of the classical and alternative C3 convertases, promoting the evasion of destruction by complement. staphylococcal enterotoxins (SEs) Secreted toxins produced by some staphylococci, which cause food poisoning and also stimulate many T cells by binding to MHC class II molecules and the Vβ domain of certain T-cell receptors, acting as superantigens. staphylococcal protein A (Spa) Staphylococcal protein that blocks the binding of the antibody Fc region with C1, thereby preventing complement activation. staphylokinase Staphylococcal protease that cleaves immunoglobulins bound to its surface, thereby preventing complement activation. STAT (signal transducers and activators of transcription) A family of seven transcription factors activated by many cytokine and growth factor receptors. STAT3 See STAT. STAT6 See STAT. statins Drug inhibitors of HMG-CoA reductase used to lower cholesterol.


Immunology_Janeway

Immunology_Janeway. STAT3 See STAT. STAT6 See STAT. statins Drug inhibitors of HMG-CoA reductase used to lower cholesterol. sterile injury Damage to tissues due to trauma, ischemia, metabolic stress, or autoimmunity, bearing many immune features similar to infection. sterilizing immunity An immune response that completely eliminates a pathogen. STIM1 A transmembrane protein that acts as a Ca2+ sensor in the endoplasmic reticulum. When Ca2+ is depleted from the endoplasmic reticulum, STIM1 is activated and induces opening of plasma membrane CRAC channels. STING (stimulator of interferon genes) A dimeric protein complex in the cytoplasm anchored to the ER membrane that functions in intracellular sensing for infection. It is activated by specific cyclic di-nucleotides to activate TBK1, which phosphorylates IRF3 to induce transcription of type I interferon genes. stress-induced self See dysregulated self.


Immunology_Janeway

Immunology_Janeway. stress-induced self See dysregulated self. stromal cells The nonlymphoid cells in central and peripheral lymphoid organs that provide soluble and cell-bound signals required for lymphocyte development, survival, and migration. subcapsular sinus (SCS) The site of lymphatic entry in lymph nodes lined by phagocytes, including subcapsular macrophages which capture particulate and opsonized antigens draining in from tissues. sulfated sialyl-LewisX A sulfated tetrasaccharide carbohydrate structure attached to many cell surface proteins, it binds the P-selectin and E-selectin molecules on the surface of cells, such as neutrophils, that mediate interactions with the endothelium. superoxide dismutase (SOD) An enzyme that converts the superoxide ion produced in the phagolysosome into hydrogen peroxide, a substrate for further reactive antimicrobial metabolites.


Immunology_Janeway

Immunology_Janeway. superoxide dismutase (SOD) An enzyme that converts the superoxide ion produced in the phagolysosome into hydrogen peroxide, a substrate for further reactive antimicrobial metabolites. suppressor of cytokine signaling (SOCS) Regulatory protein that interacts with JAK kinases to inhibit signaling by activated receptors. supramolecular activation complex (SMAC) Organized structure that forms at the point of contact between a T cell and its target cell, in which the ligand-bound antigen receptors are co-localized with other cell-surface signaling and adhesion molecules. Also known as supramolecular adhesion complex. surface immunoglobulin (sIg) The membrane-bound immunoglobulin that acts as the antigen receptor on B cells. surfactant proteins A and D (SP-A and SP-D) Acute-phase proteins that help protect the epithelial surfaces of the lung against infection.


Immunology_Janeway

Immunology_Janeway. surfactant proteins A and D (SP-A and SP-D) Acute-phase proteins that help protect the epithelial surfaces of the lung against infection. surrogate light chain A protein in pre-B cells, made up of two subunits, VpreB and λ5, that can pair with a full-length immunoglobulin heavy chain and the Igα and Igβ signaling subunits and signals for pre-B-cell differentiation. switch regions Genomic regions, several kilobases in length each, located between the JH region and the heavy-chain Cμ genes, or in equivalent positions upstream of other C-region genes (except Cδ), containing hundreds of G-rich repeated sequences that function in class switch recombination. Syk A cytoplasmic tyrosine kinase found in B cells that acts in the signaling pathway from the B-cell antigen receptor. symbiotic Relationship between two agents, typically diverse species, that confers benefits to both. sympathetic ophthalmia Autoimmune response that occurs in the other eye after one eye is damaged.


Immunology_Janeway

Immunology_Janeway. sympathetic ophthalmia Autoimmune response that occurs in the other eye after one eye is damaged. syngeneic graft A graft between two genetically identical individuals. It is accepted as self. systemic immune system Name sometimes given to the lymph nodes and spleen to distinguish them from the mucosal immune system. systemic lupus erythematosus (SLE) An autoimmune disease in which autoantibodies against DNA, RNA, and proteins associated with nucleic acids form immune complexes that damage small blood vessels, especially in the kidney. T10, T22 Murine MHC class Ib genes expressed by activated lymphocytes and recognized by a subset of γ:δ T cells. T lymphocytes (T cells) See T cell. TAB1, TAB2 An adaptor complex that binds K63 linked polyubiquitin chains. TAB1/2 complex with TAK1, targeting TAK1 to signaling scaffolds where it phosphorylates substrates such as IKKα.


Immunology_Janeway

Immunology_Janeway. TAB1, TAB2 An adaptor complex that binds K63 linked polyubiquitin chains. TAB1/2 complex with TAK1, targeting TAK1 to signaling scaffolds where it phosphorylates substrates such as IKKα. TACE (TNF-α-converting enzyme) A protease responsible for cleavage of the membrane-associated form of TNF-α, allowing cytokine release into its soluble form that can enter the systemic circulation. TACI A receptor for BAFF expressed on B cells that activates the canonical NFκB pathway. tacrolimus An immunosuppressant polypeptide drug that binds FKBPs and inactivates T cells by inhibiting calcineurin, thus blocking activation of the transcription factor NFAT. Also called FK506. TAK1 A serine-threonine kinase that is activated by phosphorylation by the IRAK complex, and that activates downstream targets such as IKKβ and MAPKs.


Immunology_Janeway

Immunology_Janeway. TAK1 A serine-threonine kinase that is activated by phosphorylation by the IRAK complex, and that activates downstream targets such as IKKβ and MAPKs. talin An intracellular protein involved in the linkage of activated integrins, such as LFA-1, to the cytoskeleton to allow changes in cellular motility and migration, such as in the diapedesis of neutrophils across the vascular endothelium. TAP1, TAP2 Transporters associated with antigen processing. ATP-binding cassette proteins that form a heterodimeric TAP-1:TAP-2 complex in the endoplasmic reticulum membrane, through which short peptides are transported from the cytosol into the lumen of the endoplasmic reticulum, where they associate with MHC class I molecules. tapasin TAP-associated protein. A key molecule in the assembly of MHC class I molecules; a cell deficient in this protein has only unstable MHC class I molecules on the cell surface.


Immunology_Janeway

Immunology_Janeway. tapasin TAP-associated protein. A key molecule in the assembly of MHC class I molecules; a cell deficient in this protein has only unstable MHC class I molecules on the cell surface. Tbet A transcription factor active in many immune cell types but most typically associated with ILC1 and TH1 function. TBK1 (TANK-binding kinase) A serine-threonine kinase activated during signaling by TLR-3 and MAVS and serving to phosphorylate and activate IRF3 for induction of type I interferon gene expression. T cell, T lymphocyte One of the two types of antigen-specific lymphocytes responsible for adaptive immune responses, the other being the B cells.


Immunology_Janeway

Immunology_Janeway. T cell, T lymphocyte One of the two types of antigen-specific lymphocytes responsible for adaptive immune responses, the other being the B cells. T cells are responsible for the cell-mediated adaptive immune reactions. They originate in the bone marrow but undergo most of their development in the thymus. The highly variable antigen receptor on T cells is called the T-cell receptor and recognizes a complex of peptide antigen bound to MHC molecules on cell surfaces. There are two main lineages of T cells: those carrying α:β receptors and those carrying γ:δ receptors. Effector T cells perform a variety of functions in an immune response, acting always by interacting with another cell in an antigen-specific manner. Some T cells activate macrophages, some help B cells produce antibody, and some kill cells infected with viruses and other intracellular pathogens. T-cell antigen receptor See T-cell receptor.


Immunology_Janeway

Immunology_Janeway. T-cell antigen receptor See T-cell receptor. T-cell areas Regions of peripheral lymphoid organs that are enriched in naive T cells and are distinct from the follicles. They are the sites at which adaptive immune responses are initiated. T-cell plasticity Flexibility in the developmental programming of CD4 T cells such that effector T-cell subsets are not irreversibly fixed in their function or the transcriptional networks that underpin those functions. T-cell receptor (TCR) The cell-surface receptor for antigen on T lymphocytes. It consists of a disulfide-linked heterodimer of the highly variable α and β chains in a complex with the invariant CD3 and ζ proteins, which have a signaling function. T cells carrying this type of receptor are often called α:βT cells. An alternative receptor made up of variable γ and δ chains is expressed with CD3 and ζ on a subset of T cells. T-cell receptor α (TCRα) and β (TCRβ) The two chains of the α:β T-cell receptor.


Immunology_Janeway

Immunology_Janeway. T-cell receptor α (TCRα) and β (TCRβ) The two chains of the α:β T-cell receptor. T-cell receptor excision circles (TRECs) Circular DNA fragments excised from the chromosome during V(D)J recombination in developing thymoctytes that are transiently retained in T cells that have recently left the thymus. T-cell zones See T-cell areas. T-DM1 An antibody-drug conjugate combining trastuzumab (Herceptin) with mertansine used to treat recurrent metastatic breast cancer previously treated with a different trastuzumab drug conjugate. TdT See terminal deoxynucleotidyl transferase. TEPs See thioester-containing proteins. terminal deoxynucleotidyl transferase (TdT) Enzyme that inserts nontemplated N-nucleotides into the junctions between gene segments in T-cell receptor and immunoglobulin V-region genes during their assembly.


Immunology_Janeway

Immunology_Janeway. tertiary immune responses Adaptive immune response provoked by a third injection of the same antigen. It is more rapid in onset and stronger than the primary response. T follicular helper (TFH) cell An effector T cell found in lymphoid follicles that provides help to B cells for antibody production and class switching. TH1 A subset of effector CD4 T cells characterized by the cytokines they produce. They are mainly involved in activating macrophages but can also help stimulate B cells to produce antibody. TH2 A subset of effector CD4 T cells that are characterized by the cytokines they produce. They are involved in stimulating B cells to produce antibody, and are often called helper CD4 T cells. TH17 A subset of CD4 T cells that are characterized by production of the cytokine IL-17. They help recruit neutrophils to sites of infection.


Immunology_Janeway

Immunology_Janeway. TH17 A subset of CD4 T cells that are characterized by production of the cytokine IL-17. They help recruit neutrophils to sites of infection. thioester-containing proteins Homologs of complement component C3 that are found in insects and are thought to have some function in insect innate immunity. thioredoxin (TRX) A set of sensor proteins normally bound to thioredoxininteracting protein (TXNIP). Oxidative stress causes thioredoxin to release TXNIP, which can mediate downstream actions. thioredoxin-interacting protein (TXNIP) See thioredoxin. thymectomy Surgical removal of the thymus. thymic anlage The tissue from which the thymic stroma develops during embryogenesis. thymic cortex The outer region of each thymic lobule in which thymic progenitor cells (thymocytes) proliferate, rearrange their T-cell receptor genes, and undergo thymic selection, especially positive selection on thymic cortical epithelial cells.


Immunology_Janeway

Immunology_Janeway. thymic stroma The epithelial cells and connective tissue of the thymus that form the essential microenvironment for T-cell development. thymic stromal lymphopoietin (TSLP) Thymic stroma-derived lymphopoietin. A cytokine thought to be involved in promoting B-cell development in the embryonic liver. It is also produced by mucosal epithelial cells in response to helminthic infections, and promotes type 2 immune responses through its actions on macrophages, ILC2s, and TH2 cells. thymocytes Developing T cells when they are in the thymus. The majority are not functionally mature and are unable to mount protective T-cell responses. thymoproteasome Specialized form of the proteasome composed of a unique subunit, β 5t, that replaces β 5i (LMP7) and associates with β 1i and β 2i in the catalytic chamber. thymus A central lymphoid organ, in which T cells develop, situated in the upper part of the middle of the chest, just behind the breastbone.


Immunology_Janeway

Immunology_Janeway. thymus A central lymphoid organ, in which T cells develop, situated in the upper part of the middle of the chest, just behind the breastbone. thymus-dependent antigens (TD) Antigens that elicit responses only in individuals that have T cells. thymus-independent antigens (TI) Antigens that can elicit antibody production without the involvement of T cells. There are two types of TI antigens: the TI-1 antigens, which have intrinsic B-cell activating activity, and the TI-2 antigens, which activate B cells by having multiple identical epitopes that cross-link the B-cell receptor. thymus leukemia antigen (TL) Nonclassical MHC class Ib molecule expressed by intestinal epithelial cells and a ligand for CD8α:α. TI-1 antigens See thymus-independent antigens. TI-2 antigens See thymus-independent antigens. tickover The low-level generation of C3b continually occurring in the blood in the absence of infection.


Immunology_Janeway

Immunology_Janeway. TI-2 antigens See thymus-independent antigens. tickover The low-level generation of C3b continually occurring in the blood in the absence of infection. tingible body macrophages Phagocytic cells engulfing apoptotic B cells, which are produced in large numbers in germinal centers at the height of an adaptive immune response. TIR (for Toll–IL-1 receptor) domain Domain in the cytoplasmic tails of the TLRs and the IL-1 receptor, which interacts with similar domains in intracellular signaling proteins. tissue-resident memory T cells (TRM) Memory lymphocytes that do not migrate after taking up residence in barrier tissues, where they are retained long term. They appear to be specialized for rapid effector function after restimulation with antigen or cytokines at sites of pathogen entry. TLR-1 Cell-surface Toll-like receptor that acts in a heterodimer with TLR-2 to recognize lipoteichoic acid and bacterial lipoproteins.


Immunology_Janeway

Immunology_Janeway. TLR-1 Cell-surface Toll-like receptor that acts in a heterodimer with TLR-2 to recognize lipoteichoic acid and bacterial lipoproteins. TLR-2 Cell-surface Toll-like receptor that acts in a heterodimer with either TLR-1 or TLR-6 to recognize lipoteichoic acid and bacterial lipoproteins. TLR-3 Endosomal Toll-like receptor that recognizes double-stranded viral RNA. TLR-4 Cell-surface Toll-like receptor that, in conjunction with the accessory proteins MD-2 and CD14, recognizes bacterial lipopolysaccharide and lipoteichoic acid. TLR-5 Cell-surface Toll-like receptor that recognizes the ﬂagellin protein of bacterial ﬂagella. TLR-6 Cell-surface Toll-like receptor that acts in a heterodimer with TLR-2 to recognize lipoteichoic acid and bacterial lipoproteins. TLR-7 Endosomal Toll-like receptor that recognizes single-stranded viral RNA. TLR-8 Endosomal Toll-like receptor that recognizes single-stranded viral RNA.


Immunology_Janeway

Immunology_Janeway. TLR-7 Endosomal Toll-like receptor that recognizes single-stranded viral RNA. TLR-8 Endosomal Toll-like receptor that recognizes single-stranded viral RNA. TLR-9 Endosomal Toll-like receptor that recognizes DNA containing unmethylated CpG. TLR-11, TLR-12 Mouse Toll-like receptor that recognizes profilin and profilin-like proteins. TNF family Cytokine family, the prototype of which is tumor necrosis factor-α (TNF or TNF-α). It contains both secreted (for example TNF-α and lymphotoxin) and membrane-bound (for example CD40 ligand) members. An autoinﬂammatory disease characterized by recurrent, periodic episodes of inﬂammation and fever caused by mutations in gene that encodes TNF receptor I. The defective TNFR-I proteins fold abnormally and accumulate in cells in such a way that they spontaneously activate production of TNF-α. See also familial Mediterranean fever.


Immunology_Janeway

Immunology_Janeway. TNF receptors Family of cytokine receptors which includes some that lead to apoptosis of the cell on which they are expressed (for example Fas and TNFR-I), whereas others lead to activation. tocilizumab Humanized anti-IL-6 receptor antibody used in treating rheumatoid arthritis. tofacitinib An inhibitor of JAK3 and JAK1 used to treat rheumatoid arthritis and under investigation in other inﬂammatory disorders. tolerance The failure to respond to an antigen. Tolerance to self antigens is an essential feature of the immune system; when tolerance is lost, the immune system can destroy self tissues, as happens in autoimmune disease. tolerant Describes the state of immunological tolerance, in which the individual does not respond to a particular antigen. tolerogenic Describes an antigen or type of antigen exposure that induces tolerance. Toll Receptor protein in Drosophila that activates the transcription factor NFκB, leading to the production of antimicrobial peptides.


Immunology_Janeway

Immunology_Janeway. Toll Receptor protein in Drosophila that activates the transcription factor NFκB, leading to the production of antimicrobial peptides. Toll-like receptors (TLRs) Innate receptors on macrophages, dendritic cells, and some other cells, that recognize pathogens and their products, such as bacterial lipopolysaccharide. Recognition stimulates the receptor-bearing cells to produce cytokines that help initiate immune responses. tonsils See lingual tonsils, palatine tonsils. toxic shock syndrome A systemic toxic reaction caused by the massive production of cytokines by CD4 T cells activated by the bacterial superantigen toxic shock syndrome toxin-1 (TSST-1), which is secreted by Staphylococcus aureus. toxic shock syndrome toxin-1 (TSST-1) See toxic shock syndrome. toxoids Inactivated toxins that are no longer toxic but retain their immunogenicity so that they can be used for immunization.


Immunology_Janeway

Immunology_Janeway. toxic shock syndrome toxin-1 (TSST-1) See toxic shock syndrome. toxoids Inactivated toxins that are no longer toxic but retain their immunogenicity so that they can be used for immunization. TRAF3 An E3 ligase that produces a K63 polyubiquitin signaling scaffold in TLR-3 signaling to induce type I interferon gene expression. TRAF6 (tumor necrosis factor receptor-associated factor 6) An E3 ligase that produces a K63 polyubiquitin signaling scaffold in TLR-4 signaling to activate the NFκB pathway. A member of the TNF cytokine family expressed on the cell surface of some cells, such as NK cells, that induces cell death in target cells by ligation of the 'death' receptors DR4 and DR5. TRAM An adaptor protein that pairs with TRIF in signaling by TLR-4. transcytosis The active transport of molecules, such as secreted IgA, through epithelial cells from one face to the other.


Immunology_Janeway

Immunology_Janeway. TRAM An adaptor protein that pairs with TRIF in signaling by TLR-4. transcytosis The active transport of molecules, such as secreted IgA, through epithelial cells from one face to the other. Transib A superfamily of transposable elements identified computationally and proposed to date back more than 500 million years and to have given rise to transposons in diverse species. transitional immunity Referring to the recognition by some adaptive immune system (e.g., MAIT, γ:δT cells) of non-peptide ligands expressed as a consequence of infection, such as various MHC class Ib molecules. transitional stages Defined stages in the development of immature B cells into mature B cells in the spleen, after which the B cell expresses B-cell co-receptor component CD21. transporters associated with antigen processing-1 and -2 (TAP1 and TAP2) See TAP1, TAP2.


Immunology_Janeway

Immunology_Janeway. transporters associated with antigen processing-1 and -2 (TAP1 and TAP2) See TAP1, TAP2. transposase An enzyme capable of cutting DNA and allowing integration and excision of transposable genetic elements into or from the genome of a host. trastuzumab Humanized antibody to HER-2/neu used in treatment of breast cancer. TRECs See T-cell receptor excision circles. TRIF An adaptor protein that alone is involved in signaling by TLR-3, and that when paired with TRAM, functions in signaling by TLR-4. TRIKA1 A complex of the E2 ubiquitin ligase UBC13 and cofactor Uve1A, that interacts with TRAF6 in forming the K63 polyubiquitin signaling scaffold in TLR signaling downstream of MyD88. TRIM21 (tripartite motif-containing 21) A cytosolic Fc receptor and E3 ligase that is activated by IgG and can ubiquitinate viral proteins after an antibody-coated virus enters the cytoplasm. TRIM25 An E3 ubiquitin ligase involved in signaling by RIG-I and MDA-5 for the activation of MAVS.


Immunology_Janeway

Immunology_Janeway. TRIM25 An E3 ubiquitin ligase involved in signaling by RIG-I and MDA-5 for the activation of MAVS. tropism The characteristic of a pathogen that describes the cell types it will infect. TSC Protein complex that acts as a GTPase-activating protein (GAP) for Rheb in its non-phosphorylated state. TSC is inactivated when phosphorylated by Akt. TSLP Thymic stroma-derived lymphopoietin. A cytokine thought to be involved in promoting B-cell development in the embryonic liver. tumor necrosis factor-α See TNF family. tumor rejection antigens Antigens on the surface of tumor cells that can be recognized by T cells, leading to attack on the tumor cells. TRAs are peptides of mutant or overexpressed cellular proteins bound to MHC class I molecules on the tumor-cell surface.


Immunology_Janeway

Immunology_Janeway. type 1 diabetes mellitus Disease in which the β cells of the pancreatic islets of Langerhans are destroyed so that no insulin is produced. The disease is believed to result from an autoimmune attack on the β cells. It is also known as insulin-dependent diabetes mellitus (IDDM), because the symptoms can be ameliorated by injections of insulin. type 1 immunity Class of effector activities aimed at elimination of intracellular pathogens. type 2 immunity Class of effector activities aimed at elimination of parasites and promoting barrier and mucosal immunity. type 3 immunity Class of effector activities aimed at elimination of extracellular pathogens such as bacteria and fungi. type I interferons The antiviral interferons IFN-α and IFN-β. type II interferon The antiviral interferon IFN-γ. type III secretion system (T3SS) Specialized appendage of Gram-negative bacteria used to aid infection of eukaryotic cells by direct secretion of effector proteins into their cytoplasm.


Immunology_Janeway

Immunology_Janeway. type III secretion system (T3SS) Specialized appendage of Gram-negative bacteria used to aid infection of eukaryotic cells by direct secretion of effector proteins into their cytoplasm. tyrosinase Enzyme in melanin synthesis pathway and frequently a tumor rejection antigen in melanoma. tyrosine phosphatases Enzymes that remove phosphate groups from phosphorylated tyrosine residues on proteins. See also CD45. tyrosine protein kinases Enzymes that specifically phosphorylate tyrosine residues in proteins. They are critical in the signaling pathways that lead to Tand B-cell activation. UBC13 See TRIKA1. ubiquitin A small protein that can be attached to other proteins and functions as a protein interaction module or to target them for degradation by the proteasome. ubiquitin ligase Enzyme that attaches ubiquitin covalently to exposed lysine residues on the surfaces of other proteins.


Immunology_Janeway

Immunology_Janeway. ubiquitin ligase Enzyme that attaches ubiquitin covalently to exposed lysine residues on the surfaces of other proteins. ubiquitin–proteasome system (UPS) A quality control system in the cell that involves K48-linked ubiquitination of target proteins that are then recognized by the proteasome for degradation. ubiquitination The process of attachment of one or many subunits of ubiquitin to a target protein, which can mediate either degradation by the proteasome, or formation of scaffolds used for signaling, depending on the nature of the linkages. UL16-binding proteins, or ULBPs See RAET1. ULBP4 See RAET1. ulcerative colitis One of the two major types of inﬂammatory bowel disease thought to result from an abnormal overresponsiveness to the commensal gut microbiota. See also Crohn’s disease. UNC93B1 A mutlipass transmembrane protein that is necessary for the normal transport of TLR-3, TLR-7, and TLR-9 from the ER, where they are assembled, to the endosome, where they function.


Immunology_Janeway

Immunology_Janeway. UNC93B1 A mutlipass transmembrane protein that is necessary for the normal transport of TLR-3, TLR-7, and TLR-9 from the ER, where they are assembled, to the endosome, where they function. unmethylated CpG dinucleotides While mammalian genomes have heavily methylated the cytosine within CpG sequences, unmethylated CpG is more typically characteristic of bacterial genomes, and is recognized by TLR-9 when encountered in the endosomal compartment. uracil-DNA glycosylase (UNG) Enzyme that removes uracil bases from DNA in a DNA repair pathway that can lead to somatic hypermutation, class switch recombination or gene conversion. urticaria The technical term for hives, which are red, itchy skin wheals usually brought on by an allergic reaction. Uve1A See TRIKA1. Vα Variable region from the TCRα chain. Vβ Variable region from the TCRβ chain.


Immunology_Janeway

Immunology_Janeway. Uve1A See TRIKA1. Vα Variable region from the TCRα chain. Vβ Variable region from the TCRβ chain. vaccination The deliberate induction of adaptive immunity to a pathogen by injecting a dead or attenuated (nonpathogenic) live form of the pathogen or its antigens (a vaccine). variability plot A measure of the difference between the amino acid sequences of different variants of a given protein. The most variable proteins known are antibodies and T-cell receptors. variable Ig domains (V domains) The amino-terminal protein domain of the polypeptide chains of immunoglobulins and T-cell receptor, which is the most variable part of the chain. variable lymphocyte receptors (VLRs) Nonimmunoglobulin LRR-containing variable receptors and secreted proteins expressed by the lymphocyte-like cells of the lamprey. They are generated by a process of somatic gene rearrangement.


Immunology_Janeway

Immunology_Janeway. variable region The region of an immunoglobulin or T-cell receptor that is formed of the amino-terminal domains of its component polypeptide chains. These are the most variable parts of the molecule and contain the antigen-binding sites. variolation The intentional inhalation of or skin infection with material taken from smallpox pustules of an infected person for the purpose of deriving protective immunity. VCAM-1 An adhesion molecule expressed by vascular endothelium at sites of inﬂammation; it binds the integrin VLA-4, which allows effector T cells to enter sites of infection. V(D)J recombinase A multiprotein complex containing RAG-1 and RAG-2, as well as other proteins involved in cellular DNA repair. V(D)J recombination The process exclusive to developing lymphocytes in vertebrates, that recombines different gene segments into sequences encoding complete protein chains of immunoglobulins and T-cell receptors.


Immunology_Janeway

Immunology_Janeway. vesicular compartments One of several major compartments within cells, composed of the endoplasmic reticulum, Golgi, endosomes, and lysosomes. V gene segments Gene segments in immunoglobulin and T-cell receptor loci that encode the first 95 amino acids or so of the protein chain. There are multiple different V gene segments in the germline genome. To produce a complete exon encoding a V domain, one V gene segment must be rearranged to join up with a J or a rearranged DJ gene segment. viral entry inhibitors Drugs that inhibit the entry of HIV into its host cells. viral integrase inhibitors Drugs that inhibit the action of the HIV integrase, so that the virus cannot integrate into the host-cell genome. viral protease Enzyme encoded by the human immunodeficiency virus that cleaves the long polyprotein products of the viral genes into individual proteins.


Immunology_Janeway

Immunology_Janeway. viral protease Enzyme encoded by the human immunodeficiency virus that cleaves the long polyprotein products of the viral genes into individual proteins. viral set point In human immunodeficiency virus infection, the level of HIV virions persisting in the blood after the acute phase of infection has passed. virus Pathogen composed of a nucleic acid genome enclosed in a protein coat. Viruses can replicate only in a living cell, because they do not possess the metabolic machinery for independent life. virus-neutralizing antibodies Antibodies that block the ability of a virus to establish infection of cells. vitronectin See S-protein. VLRs See variable lymphocyte receptors. VpreB See surrogate light chain. WAS See Wiskott–Aldrich syndrome. WASp The protein defective in patients with Wiskott–Aldrich syndrome. When activated, WASp promotes actin polymerization. Weibel–Palade bodies Granules within endothelial cells that contain P-selectin.


Immunology_Janeway

Immunology_Janeway. Weibel–Palade bodies Granules within endothelial cells that contain P-selectin. wheal-and-flare reaction A skin reaction observed in an allergic individual when an allergen to which the individual has been sensitized is injected into the dermis. It consists of a raised area of skin containing edema ﬂuid, and a spreading, red, itchy inﬂammatory reaction around it. white pulp The discrete areas of lymphoid tissue in the spleen. Wiskott–Aldrich syndrome (WAS) An immunodeficiency disease characterized by defects in the cytoskeleton of cells due to a mutation in the protein WASp, which is involved in interactions with the actin cytoskeleton. Patients with this disease are highly susceptible to infections with pyogenic bacteria due to defects in T-follicular helper cell interactions with B cells.


Immunology_Janeway

Immunology_Janeway. XBP1 (X-box binding protein 1) A transcription factor that induces genes required for optimal protein secretion by plasma cells, and is part of the unfolded protein response. XBP1 mRNA is spliced from an inactive to an active form by signals produced by ER stress. XCR1 A chemokine receptor selectively expressed by a subset of dendritic cells that are specialized for cross-presentation whose development requires the transcription factor BATF3. xenografts Grafted organs taken from a different species than the recipient. xenoimmunity In the context of immune-mediated disease, refers to immunity directed against foreign antigens of non-human species, such as bacteria-derived antigens of the commensal microbiota that are targets in inﬂammatory bowel disease (IBD). xeroderma pigmentosum Several autosomal recessive diseases caused by defects in repair of ultraviolet light-induced DNA damage. Defects in Polη cause type V xeroderma pigmentosum. xid See X-linked immunodeficiency.


Immunology_Janeway

Immunology_Janeway. xid See X-linked immunodeficiency. X-linked agammaglobulinemia (XLA) A genetic disorder in which B-cell development is arrested at the pre-B-cell stage and no mature B cells or antibodies are formed. The disease is due to a defect in the gene encoding the protein tyrosine kinase Btk, which is encoded on the X chromosome. X-linked hyper IgM syndrome See CD40 ligand deficiency. A syndrome with some features resembling hyper IgM syndrome. It is caused by mutations in the protein NEMO, a component of the NFκB signaling pathway. Also called NEMO deficiency. X-linked immunodeficiency An immunodeficiency disease in mice due to defects in the protein tyrosine kinase Btk. Shares the gene defect with X-linked agammaglobulinemia in humans, but leads to a milder B cell defect than seen in the human disease.


Immunology_Janeway

Immunology_Janeway. X-linked lymphoproliferative (XLP) syndrome Rare immunodeficiency diseases that result from mutations in the gene SH2D1A (XLP1) or XIAP (XLP2). Boys with this deficiency typically develop overwhelming Epstein–Barr virus infection during childhood, and sometimes lymphomas. An immunodeficiency disease in which T-cell development fails at an early intrathymic stage and no production of mature T cells or T-cell dependent antibody occurs. It is due to a defect in a gene that encodes the γc chain shared by the receptors for several different cytokines. XLP See X-linked lymphoproliferative syndrome. XRCC4 A protein that functions in NHEJ DNA repair by interacting with DNA ligase IV and Ku70/80 at double-strand breaks. ζ chain One of the signaling chains associated with the T-cell receptor that has three ITAM motifs in its cytoplasmic tail.


Immunology_Janeway

Immunology_Janeway. ζ chain One of the signaling chains associated with the T-cell receptor that has three ITAM motifs in its cytoplasmic tail. ZAP-70 (ζ-chain-associated protein) A cytoplasmic tyrosine kinase found in T cells that binds to the phosphorylated ζ chain of the T-cell receptor and is a key enzyme in signaling T-cell activation. ZFP318 A spliceosome protein expressed in mature and activated B cells, but not immature B cells, that favors splicing from the rearranged VDJ exon of immunoglobulin heavy chain to the Cδ exon, thereby promoting expression of surface IgD. zoonotic Describes a disease of animals that can be transmitted to humans. zymogens An inactive form of an enzyme, usually a protease, that must be modified in some way, for example by selective cleavage of the protein chain, before it can become active.