Immunology_Janeway

Immunology_Janeway. immunological ignorance A form of self-tolerance in which reactive lymphocytes and their target antigen are both detectable within an individual, yet no autoimmune attack occurs. immunological memory The ability of the immune system to respond more rapidly and more effectively on a second encounter with an antigen. Immunological memory is specific for a particular antigen and is long-lived. immunological synapse The highly organized interface that develops between a T cell and the target cell it is in contact with, formed by T-cell receptors binding to antigen and cell-adhesion molecules binding to their counterparts on the two cells. Also known as the supramolecular adhesion complex. immunological tolerance See tolerance.


Immunology_Janeway

Immunology_Janeway. immunological tolerance See tolerance. immunologically privileged sites Certain sites in the body, such as the brain, that do not mount an immune response against tissue allografts. Immunological privilege can be due both to physical barriers to cell and antigen migration and to the presence of immunosuppressive cytokines. immunology The study of all aspects of host defense against infection and also of the adverse consequences of immune responses. immunomodulatory therapy Treatments that seek to modify an immune response in a beneficial way, for example to reduce or prevent an autoimmune or allergic response. immunophilins See cyclophilins, FK-binding proteins. immunoproteasome A form of proteasome found in cells exposed to interferons. It contains three subunits that are different from the normal proteasome.


Immunology_Janeway

Immunology_Janeway. immunoproteasome A form of proteasome found in cells exposed to interferons. It contains three subunits that are different from the normal proteasome. immunoreceptor tyrosine-based activation motif (ITAM) Sequence motifs in the signaling chains of receptors, such as antigen receptors on lymphocytes, that are the site of tyrosine phosphorylation after receptor activation, leading to recruitment of other signaling proteins. immunoreceptor tyrosine-based inhibition motif (ITIM) Sequence motifs in the signaling chains of inhibitory receptors that are sites of tyrosine phosphorylation, leading to inhibitory signaling, such as through recruitment of phosphatases that remove phosphate groups added by tyrosine kinases. immunoreceptor tyrosine-based switch motif (ITSM) A sequence motif present in the cytoplasmic tails of some inhibitor receptors.


Immunology_Janeway

Immunology_Janeway. immunoreceptor tyrosine-based switch motif (ITSM) A sequence motif present in the cytoplasmic tails of some inhibitor receptors. immunotoxin Antibodies that are chemically coupled to toxic proteins usually derived from plants or microbes. The antibody targets the toxin moiety to the required cells. indirect allorecognition Recognition of a grafted tissue that involves the uptake of allogeneic proteins by the recipient’s antigen-presenting cells and their presentation to T cells by self MHC molecules. indoleamine 2,3-dioxygenase (IDO) Enzyme expressed by immune cells and some tumors that catabolizes tryptophan into kynurenine metabolites that can have immunosuppressive functions. induced pluripotent stem cells (iPS cells) Pluripotent stem cells that are derived from adult somatic cells by the introduction of a cocktail of transcription factors.


Immunology_Janeway

Immunology_Janeway. induced pluripotent stem cells (iPS cells) Pluripotent stem cells that are derived from adult somatic cells by the introduction of a cocktail of transcription factors. infectious mononucleosis The common form of infection with the Epstein–Barr virus. It consists of fever, malaise, and swollen lymph nodes. Also called glandular fever. inflammasome A pro-inﬂammatory protein complex that is formed after stimulation of the intracellular NOD-like receptors. Production of an active caspase in the complex processes cytokine proproteins into active cytokines. inflammation General term for the local accumulation of ﬂuid, plasma proteins, and white blood cells that is initiated by physical injury, infection, or a local immune response. inflammatory bowel disease (IBD) General name for a set of inﬂammatory conditions in the gut, such as Crohn’s disease and colitis, that have an immunological component.


Immunology_Janeway

Immunology_Janeway. inflammatory bowel disease (IBD) General name for a set of inﬂammatory conditions in the gut, such as Crohn’s disease and colitis, that have an immunological component. inflammatory cells Cells such as macrophages, neutrophils, and effector TH1 lymphocytes that invade inﬂamed tissues and contribute to the inﬂammation. inflammatory chemokines Chemokines that are produced in response to infection or injury to direct the localization of immune cells to sites of inﬂammation. inflammatory inducers Chemical structures that indicate the presence of invading microbes or cellular damage, such as bacterial lipopolysaccharides, extracellular ATP, or urate crystals. inflammatory mediators Chemicals such as cytokines produced by immune cells that act on target cells to promote defense against microbes. inflammatory monocytes An activated form of monocyte producing a variety of pro-inﬂammatory cytokines. inflammatory response See inflammation.


Immunology_Janeway

Immunology_Janeway. inflammatory monocytes An activated form of monocyte producing a variety of pro-inﬂammatory cytokines. inflammatory response See inflammation. infliximab Chimeric antibody to TNF-α used in the treatment of inﬂammatory diseases, such as Crohn's disease and rheumatoid arthritis. inherited immunodeficiency diseases See primary immunodeficiencies. inhibitory receptors On NK cells, receptors whose stimulation results in suppression of the cell’s cytotoxic activity. initiator caspases Proteases that promote apoptosis by cleaving and activating other caspases. iNKT See invariant NKT cells.


Immunology_Janeway

Immunology_Janeway. initiator caspases Proteases that promote apoptosis by cleaving and activating other caspases. iNKT See invariant NKT cells. innate immunity The various innate resistance mechanisms that are encountered first by a pathogen, before adaptive immunity is induced, such as anatomical barriers, antimicrobial peptides, the complement system, and macrophages and neutrophils carrying nonspecific pathogen-recognition receptors. Innate immunity is present in all individuals at all times, does not increase with repeated exposure to a given pathogen, and discriminates between groups of similar pathogens, rather than responding to a particular pathogen. Cf. adaptive immunity. innate lymphoid cells (ILCs) See ILCs. innate recognition receptors General term for a large group of proteins that recognize many different inﬂammatory inducers and that are encoded in the germline and do not need gene rearrangement in somatic cells to be expressed.


Immunology_Janeway

Immunology_Janeway. inositol 1,4,5-trisphosphate (IP3) A soluble second messenger produced by the cleavage of membrane inositol phospholipids by phospholipase C-γ. It acts on receptors in the endoplasmic reticulum membrane, resulting in the release of stored Ca2+ into the cytosol. integrin Heterodimeric cell-surface proteins involved in cell–cell and cell–matrix interactions. They are important in adhesive interactions between lymphocytes and antigen-presenting cells and in lymphocyte and leukocyte adherence to blood vessel walls and migration into tissues. integrin α4:β7 Integrin binding to VCAM-1, MAdCAM-1, and fibronectin and expressed by various cells, such as IELs, that traffic to intestinal lamina propria. intercellular adhesion molecules (ICAMs) See ICAMs. interdigitating dendritic cells See dendritic cells.


Immunology_Janeway

Immunology_Janeway. intercellular adhesion molecules (ICAMs) See ICAMs. interdigitating dendritic cells See dendritic cells. interferon regulatory factor (IRF) A family of nine transcription factors that regulate a variety of immune responses. For example, IRF3 and IRF7 are activated as a result of signaling from some TLRs. Several IRFs promote expression of the genes for type I interferons. interferon stimulated genes (ISGs) A category of gene induced by interferons, which include many that promote innate defense against pathogens, such as oligoadenylate synthetase, PKR, and the Mx, IFITs, and IFITM proteins. interferon-α receptor (IFNAR) This receptor recognizes IFN-α and IFN-β to activate STAT1 and STAT2 and induce expression of many ISGs. interferon-induced transmembrane protein (IFITM) See IFITM. interferon-producing cells (IPCs) See plasmacytoid dendritic cells.


Immunology_Janeway

Immunology_Janeway. interferon-induced transmembrane protein (IFITM) See IFITM. interferon-producing cells (IPCs) See plasmacytoid dendritic cells. interferons (IFNs) Several related families of cytokines originally named for their interference of viral replication. IFN-α and IFN-β are antiviral in their effects; IFN-γ has other roles in the immune system. intergenic control regions Sites in non-coding regions of genes that control their expression and rearrangement by interactions with transcription factors and chromatin-modifying proteins. interleukin (IL) A generic name for cytokines produced by leukocytes. The more general term cytokine is used in this book, but the term interleukin is used in the naming of specific cytokines such as IL-2. Some key interleukins are listed in the glossary under their abbreviated names, for example IL-1β and IL-2. Cytokines are listed in Appendix III.


Immunology_Janeway

Immunology_Janeway. intraepithelial lymphocytes (IELs) Lymphocytes present in the epithelium of mucosal surfaces such as the gut. They are predominantly T cells, and in the gut are predominantly CD8 T cells. intrathymic dendritic cells See dendritic cells. intrinsic pathway of apoptosis Signaling pathway that mediates apoptosis in response to noxious stimuli including UV irradiation, chemotherapeutic drugs, starvation, or lack of the growth factors required for survival. It is initiated by mitochondrial damage. Also called the mitochondrial pathway of apoptosis. invariant chain (Ii, CD74) A polypeptide that binds in the peptide-binding cleft of newly synthesized MHC class II proteins in the endoplasmic reticulum and blocks other peptides from binding there. It is degraded in the endosome, allowing for loading of antigenic peptides there.


Immunology_Janeway

Immunology_Janeway. invariant NKT cells (iNKT cells) A type of innate-like lymphocyte that carries a T-cell receptor with an invariant α chain and a β chain of limited diversity that recognizes glycolipid antigens presented by CD1 MHC class Ib molecules. This cell type also carries the surface marker NK1.1, which is usually associated with NK cells. IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome. A very rare inherited condition in which CD4 CD25 regulatory T cells are lacking as a result of a mutation in the gene for the transcription factor FoxP3, leading to the development of autoimmunity. ipilimumab Antibody to human CTLA-4 used to treat melanoma, and first checkpoint blockade immunotherapy.


Immunology_Janeway

Immunology_Janeway. ipilimumab Antibody to human CTLA-4 used to treat melanoma, and first checkpoint blockade immunotherapy. Ir (immune response) genes An archaic term for genetic polymorphisms controlling the intensity of the immune response to a particular antigen, now known to result from allelic differences in MHC molecules, especially MHC class II molecules, that inﬂuence binding of particular peptides. IRAK1, IRAK4 Protein kinases that are part of the intracellular signaling pathways leading from TLRs. IRAK4 deficiency An immunodeficiency characterized by recurrent bacterial infections, caused by inactivating mutations in the IRAK4 gene that result in a block in TLR signaling. IRF9 A member of the IRF family of transcription factors that interacts with activated STAT1 and STAT2 to form the complex called ISGF3, which induces transcription of many ISGs.


Immunology_Janeway

Immunology_Janeway. IRF9 A member of the IRF family of transcription factors that interacts with activated STAT1 and STAT2 to form the complex called ISGF3, which induces transcription of many ISGs. IRGM3 A protein that functions in the maintenance and storage of neutral lipid droplets in many types of cells in association with adipose differentiation related protein. irradiation-sensitive SCID (IR-SCID) A type of severe combined immunodeficiency due to mutations in DNA repair proteins, such as Artemis, that causes abnormal sensitivity to ionizing radiation and defects in V(D)J recombination. ISGF3 See IRF9. isoforms Different forms of the same protein, for example the different forms encoded by different alleles of the same gene. isolated lymphoid follicles (ILF) A type of organized lymphoid tissue in the gut wall that is composed mainly of B cells. isolation membrane See phagophore.


Immunology_Janeway

Immunology_Janeway. isolated lymphoid follicles (ILF) A type of organized lymphoid tissue in the gut wall that is composed mainly of B cells. isolation membrane See phagophore. isotype The designation of an immunoglobulin chain in respect of the type of constant region it has. Light chains can be of either κ or λ isotype. Heavy chains can be of μ, δ, γ, α, or ε isotype. The different heavy-chain isotypes have different effector functions and determine the class and functional properties of antibodies (IgM, IgD, IgG, IgA, and IgE, respectively). isotype switching See class switching. isotypic exclusion Describes the use of one or other of the light-chain isotypes, κ or λ, by a given B cell or antibody. JAK inhibitors (Jakinibs) Small molecule kinase inhibitors with relative selectivity for one or more of the JAK kinases.


Immunology_Janeway

Immunology_Janeway. JAK inhibitors (Jakinibs) Small molecule kinase inhibitors with relative selectivity for one or more of the JAK kinases. Janus kinase (JAK) family Enzymes of the JAK–STAT intracellular signaling pathways that link many cytokine receptors with gene transcription in the nucleus. The kinases phosphorylate STAT proteins in the cytosol, which then move to the nucleus and activate a variety of genes. J chain Small polypeptide chain made by B cells that attaches to polymeric immunoglobulins IgM and IgA by disulfide bonds, and is essential for formation of the binding site for the polymeric immunoglobulin receptor. JNK See Jun kinase. Job’s syndrome See hyper IgE syndrome.


Immunology_Janeway

Immunology_Janeway. JNK See Jun kinase. Job’s syndrome See hyper IgE syndrome. joining gene segment, J gene segment Short DNA sequences that encode the J regions of immunoglobulin and T-cell receptor variable domains. In a rearranged light-chain, TCRα, or TCRγ genes, the J gene segment is joined to a V gene segment. In a rearranged heavy-chain, TCRβ, or TCRδ locus, a J gene segment is joined to a D gene segment. Jun kinase A protein kinase that phosphorylates the transcription factor c-Jun, enabling it to bind to c-Fos to form the AP-1 transcription factor. junctional diversity The variability in sequence present in antigen-specific receptors that is created during the process of joining V, D, and J gene segments and which is due to imprecise joining and insertion of nontemplated nucleotides at the joins between gene segments. κ chain One of the two classes or isotypes of immunoglobulin light chains.


Immunology_Janeway

Immunology_Janeway. κ chain One of the two classes or isotypes of immunoglobulin light chains. K63-linkages In polyubiquitin chains, the covalent ligation of lysine 63 amino group of one ubiquitin protein with the carboxy terminus of a second ubiquitin. This type of linkage is most associated with activation of signaling by formation of a scaffold recognized by signaling adaptors such as TAB1/2. killer cell immunoglobulin-like receptors (KIRs) Large family of receptors present on NK cells, through which the cells’ cytotoxic activity is controlled. The family contains both activating and inhibitory receptors. killer cell lectin-like receptors (KLRs) Large family of receptors present on NK cells, through which the cells’ cytotoxic activity is controlled. The family contains both activating and inhibitory receptors.


Immunology_Janeway

Immunology_Janeway. kinase suppressor of Ras A scaffold protein in the Raf–MEK1–Erk MAPkinase cascade that binds to all three members following antigen receptor signaling to facilitate their interactions and to accelerate the signaling cascade. kinin system An enzymatic cascade of plasma proteins that is triggered by tissue damage to produce several inﬂammatory mediators, including the vasoactive peptide bradykinin. Kostmann’s disease A form of severe congenital neutropenia, an inherited condition in which the neutrophil count is low. In Kostmann’s disease, this is due to a deficiency of the mitochondrial protein HAX1, which leads to apoptosis of developing myeloid cells and persistent neutropenia. KSR See kinase suppressor of Ras. Ku A DNA repair protein required for immunoglobulin and T-cell receptor gene rearrangement. Kupffer cells Phagocytes lining the hepatic sinusoids; they remove debris and dying cells from the blood, but are not known to elicit immune responses.


Immunology_Janeway

Immunology_Janeway. Kupffer cells Phagocytes lining the hepatic sinusoids; they remove debris and dying cells from the blood, but are not known to elicit immune responses. kynurenine metabolites Various compounds derived from tryptophan through the actions of the enzymes indolamine-2,3-dioxygenase (IDO) or tryptophan-2,3-dioxygenase (TDO) expressed in various immune cells or the liver. λ chain One of the two classes or isotypes of immunoglobulin light chains. λ5 See surrogate light chain. L-selectin Adhesion molecule of the selectin family found on lymphocytes. L-selectin binds to CD34 and GlyCAM-1 on high endothelial venules to initiate the migration of naive lymphocytes into lymphoid tissue. lamellar bodies Lipid-rich secretory organelles in keratinocytes and lung pneumocytes that release β-defensins into the extracellular space. lamina propria A layer of connective tissue underlying a mucosal epithelium. It contains lymphocytes and other immune-system cells.


Immunology_Janeway

Immunology_Janeway. lamina propria A layer of connective tissue underlying a mucosal epithelium. It contains lymphocytes and other immune-system cells. large pre-B cell Stage of B-cell development immediately after the pro-B cell, in which the cell expresses the pre-B-cell receptor and undergoes several rounds of division. LAT See linker for activation of T cells. late-phase reaction Allergic reactions that occurs several hours after initial encounter with an antigen. Thought to be manifestations of recruitment of multiple leukocyte subsets to the site of allergen exposure. late pro-B cell Stage in B-cell development in which VH to DJH joining occurs. latency A state in which a virus infects a cell but does not replicate. Lck An Src-family tyrosine kinase that associates with the cytoplasmic tails of CD4 and CD8 and phosphorylates the cytoplasmic tails of the T-cell receptor signaling chains, thus helping to activate signaling from the T-cell receptor complex once antigen has bound.


Immunology_Janeway

Immunology_Janeway. lectin A carbohydrate-binding protein. lectin pathway Complement activation pathway that is triggered by mannose-binding lectins (MBLs) or ficolins bound to bacteria. lentiviruses A group of retroviruses that include the human immunodeficiency virus, HIV-1. They cause disease after a long incubation period. lethal factor An endopeptidase produced by Bacillus anthracis that cleaves NLRP1, inducing cell death within the infected cell, typically a macrophage. leucine-rich repeat (LRR) Protein motifs that are repeated in series to form, for example, the extracellular portions of Toll-like receptors. leukocyte A white blood cell. Leukocytes include lymphocytes, polymorphonuclear leukocytes, and monocytes.


Immunology_Janeway

Immunology_Janeway. leukocyte A white blood cell. Leukocytes include lymphocytes, polymorphonuclear leukocytes, and monocytes. leukocyte adhesion deficiencies (LADs) A class of immunodeficiency diseases in which the ability of leukocytes to enter sites infected by extracellular pathogens is affected, imparing elimination of infection. There are several different causes, including a deficiency of the common β chain of the leukocyte integrins. leukocyte adhesion deficiency type 2 Disease causes by defects in the production of sulfated sialyl-LewisX that prevent neutrophils from interacting with Pand E-selectin, eliminating their ability to migrate properly to sites of infection.


Immunology_Janeway

Immunology_Janeway. leukocyte functional antigens (LFAs) Cell-adhesion molecules on leukocytes that were initially defined using monoclonal antibodies. LFA-1 is a β2 integrin; LFA-2 (now usually called CD2) is a member of the immunoglobulin superfamily, as is LFA-3 (now called CD58). LFA-1 is particularly important in T-cell adhesion to endothelial cells and antigen-presenting cells. leukocyte receptor complex (LRC) A large cluster of immunoglobulin-like receptor genes that includes the killer cell immunoglobulin-like receptor (KIR) genes. leukocytosis The presence of increased numbers of leukocytes in the blood. It is commonly seen in acute infection. leukotrienes Lipid mediators of inﬂammation that are derived from arachidonic acid. They are produced by macrophages and other cells. LFA-1 See leukocyte functional antigens. LGP2 A member of the RLR family, it cooperates with RIG-I and MDA-5 in the recognition of viral RNA.


Immunology_Janeway

Immunology_Janeway. LFA-1 See leukocyte functional antigens. LGP2 A member of the RLR family, it cooperates with RIG-I and MDA-5 in the recognition of viral RNA. licensing The activation of a dendritic cell so that it is able to present antigen to naive T cells and activate them. light chain, L chain The smaller of the two types of polypeptide chains that make up an immunoglobulin molecule. It consists of one V and one C domain, and is disulfide-bonded to the heavy chain. There are two classes, or isotypes, of light chain, known as κ and λ, which are produced from separate genetic loci. light-chain variable region (VL) Referring to the V region of the light chain of an immunoglobulin. light zone See germinal center. lingual tonsils Paired masses of organized peripheral lymphoid tissue situated at the base of the tongue, in which adaptive immune responses can be initiated. They are part of the mucosal immune system. See also palatine tonsils.


Immunology_Janeway

Immunology_Janeway. linked recognition The rule that for a helper T cell to be able to activate a B cell, the epitopes recognized by the B cell and the helper T cell have to be derived from the same antigen (that is, they must originally have been physically linked). linker for activation of T cells A cytoplasmic adaptor protein with several tyrosines that become phosphorylated by the tyrosine kinase ZAP-70. It helps to coordinate downstream signaling events in T-cell activation. LIP10 A cleaved fragment of invariant chain retaining the transmembrane segments that remains bound to MHC class II proteins and helps target the complex to the endosome. LIP22 The initial cleaved fragment of invariant chain bound to MHC class II molecules. lipid bodies Storage organelles rich in neutral lipids within the cytoplasm. lipocalin-2 An antimicrobial peptide produced in abundance by neutrophils and mucosal epithelial cells that inhibits bacterial and fungal growth by limiting availability of iron.


Immunology_Janeway

Immunology_Janeway. lipocalin-2 An antimicrobial peptide produced in abundance by neutrophils and mucosal epithelial cells that inhibits bacterial and fungal growth by limiting availability of iron. lipopeptide antigens A diverse set of antigens derived from microbial lipids typically presented by nonclassical MHC class Ib molecules such as CD1 molecules to invariant T-cell populations, including iNKT cells. lipopolysaccharide (LPS) The surface lipopolysaccharide of Gram-negative bacteria, which stimulates TLR-4 on macrophages and dendritic cells. lipoteichoic acids Components of bacterial cell walls that are recognized by Toll-like receptors. long-term non-progressors HIV-infected individuals who mount an immune response that controls viral loads such that they do not progress to AIDS despite the absence of antiretroviral therapy. See also elite controllers. LPS-binding protein Protein in blood and extracellular ﬂuid that binds bacterial lipopolysaccharide (LPS) shed from bacteria.


Immunology_Janeway

Immunology_Janeway. LPS-binding protein Protein in blood and extracellular ﬂuid that binds bacterial lipopolysaccharide (LPS) shed from bacteria. Ly49 receptors A family of C-type lectins expressed by mouse, but not human, NK cells. These can be either activating or inhibitory in function. Ly49a See Ly49 receptors. Ly49H See Ly49 receptors. Ly108 See SLAM. lymph The extracellular ﬂuid that accumulates in tissues and is drained by lymphatic vessels that carry it through the lymphatic system to the thoracic duct, which returns it to the blood. lymph nodes A type of peripheral lymphoid organ present in many locations throughout the body where lymphatic vessels converge. lymphatic system The system of lymph-carrying vessels and peripheral lymphoid tissues through which extracellular ﬂuid from tissues passes before it is returned to the blood via the thoracic duct. lymphatic vessels, lymphatics Thin-walled vessels that carry lymph.


Immunology_Janeway

Immunology_Janeway. lymphatic vessels, lymphatics Thin-walled vessels that carry lymph. lymphoblast A lymphocyte that has enlarged after activation and has increased its rate of RNA and protein synthesis, but is not yet fully differentiated. lymphocyte A class of white blood cells that bear variable cell-surface receptors for antigen and are responsible for adaptive immune responses. There are two main types—B lymphocytes (B cells) and T lymphocytes (T cells)—which mediate humoral and cell-mediated immunity, respectively. On antigen recognition, a lymphocyte enlarges to form a lymphoblast and then proliferates and differentiates into an antigen-specific effector cell. lymphocyte receptor repertoire All the highly variable antigen receptors carried by B and T lymphocytes. lymphoid Describes tissues composed mainly of lymphocytes.


Immunology_Janeway

Immunology_Janeway. lymphocyte receptor repertoire All the highly variable antigen receptors carried by B and T lymphocytes. lymphoid Describes tissues composed mainly of lymphocytes. lymphoid organs Organized tissues characterized by very large numbers of lymphocytes interacting with a nonlymphoid stroma. The central, or primary, lymphoid organs, where lymphocytes are generated, are the thymus and bone marrow. The main peripheral, or secondary, lymphoid organs, in which adaptive immune responses are initiated, are the lymph nodes, spleen, and mucosa-associated lymphoid organs such as tonsils and Peyer’s patches. lymphoid tissue Tissue composed of large numbers of lymphocytes. lymphoid tissue inducer (LTi) cells Cells of the blood lineage, which arise in the fetal liver and are carried in the blood to sites where they will form lymph nodes and other peripheral lymphoid organs. lymphopenia Abnormally low levels of lymphocytes in the blood.


Immunology_Janeway

Immunology_Janeway. lymphopenia Abnormally low levels of lymphocytes in the blood. lymphopoiesis The differentiation of lymphoid cells from a common lymphoid progenitor. lymphotoxins (LTs) Cytokines of the tumor necrosis factor (TNF) family that are directly cytotoxic for some cells. They occur as trimers of LT-α chains (LT-α3) and heterotrimers of LT-α and LT-β chains (LT-α2:β1). lysogenic phase The phase of the viral life cycle in which the virus genome integrates into the host cell genome but remains dormant, employing mechanisms to avoid destroying its cellular host. lysozyme Antimicrobial enzyme that degrades bacterial cell walls. lytic phase, productive phase The phase of the viral life cycle in which there is active viral replication followed by destruction of the infected host cell as the virus escapes to infect new target cells.


Immunology_Janeway

Immunology_Janeway. M1 macrophages The name sometimes given to ‘classically’ activated macrophages, which develop in the context of type 1 responses and have pro-inﬂammatory properties. M2 macrophages The name sometimes given to ‘alternatively’ activated macrophages, which develop in in the context of type 2 responses (e.g., parasite infection) and promote tissue remodeling and repair. macroautophagy The engulfment by a cell of large quantities of its own cytoplasm, which is then delivered to the lysosomes for degradation. macrophages Large mononuclear phagocytic cells present in most tissues that have many functions, such as scavenger cells, pathogen-recognition cells, production of pro-inﬂammatory cytokines. Macrophages arise both embryonically and from bone marrow precursors throughout life.


Immunology_Janeway

Immunology_Janeway. macropinocytosis A process in which large amounts of extracellular ﬂuid are taken up into an intracellular vesicle. This is one way in which dendritic cells can take up a wide variety of antigens from their surroundings. MAdCAM-1 Mucosal cell-adhesion molecule-1. A mucosal addressin that is recognized by the lymphocyte surface proteins L-selectin and VLA-4, enabling the specific homing of lymphocytes to mucosal tissues. MAIT cells See mucosal associated invariant T cells. major basic protein Protein released by activated eosinophils that acts on mast cells and basophils to cause their degranulation. major histocompatibility complex (MHC) A cluster of genes on human chromosome 6 that encodes a set of membrane glycoproteins called the MHC molecules. The MHC also encodes proteins involved in antigen processing and other aspects of host defense. The genes for the MHC molecules are the most polymorphic in the human genome, having large numbers of alleles at the various loci.


Immunology_Janeway

Immunology_Janeway. MAL An adaptor protein that associates with MyD88 in signaling by TLR-2/1, TLR-2/6, and TLR-4. mannose-binding lectin (MBL) Mannose-binding protein present in the blood. It can opsonize pathogens bearing mannose on their surfaces and can activate the complement system via the lectin pathway, an important part of innate immunity. mannose receptor (MR) A receptor on macrophages that is specific for mannose-containing carbohydrates that occur on the surfaces of pathogens but not on host cells. mantle zone A rim of B lymphocytes that surrounds lymphoid follicles.


Immunology_Janeway

Immunology_Janeway. mantle zone A rim of B lymphocytes that surrounds lymphoid follicles. Mantoux test A screening test for tuberculosis in which a sterile-filtered glycerol extract of Mycobacterium tuberculosis bacilli (Tb) is injected intradermally and the result is read 48–72 hours later. Induration, firm swelling caused by infiltration into the skin of inﬂammatory cells, can indicate previous exposure to Tb, either prior vaccination or current infection of M. tuberculosis. Generally, induration at the site of injection greater than 10 mm in diameter indicates the need for additional tests to assess whether infection with Tb is present. MAP kinase (MAPK) See mitogen-activated protein kinase. MARCO (macrophage receptor with a collagenous structure) See scavenger receptor). marginal sinus A blood-filled vascular network that branches from the central arteriole and demarcates each area of white pulp in the spleen.


Immunology_Janeway

Immunology_Janeway. marginal sinus A blood-filled vascular network that branches from the central arteriole and demarcates each area of white pulp in the spleen. marginal zone Area of lymphoid tissue lying at the border of the white pulp in the spleen. marginal zone B cells A unique population of B cells found in the spleen marginal zones; they do not circulate and are distinguished from conventional B cells by a distinct set of surface proteins. MASP-1, MASP-2, MASP-3 Serine proteases of the classical and lectin pathway of complement activation that bind to C1q, ficolins, and mannosebinding lectin, and function in their activation to cleave C4.


Immunology_Janeway

Immunology_Janeway. mast cells A large granule-rich cell found in connective tissues throughout the body, most abundantly in the submucosal tissues and the dermis. The granules store bioactive molecules including the vasoactive amine histamine, which are released on mast-cell activation. Mast cells are thought to be involved in defenses against parasites and they have a crucial role in allergic reactions. mastocytosis The overproduction of mast cells. mature B cell B cell that expresses IgM and IgD on its surface and has gained the ability to respond to antigen. MAVS (mitochondrial antiviral signaling protein) A CARD-containing adaptor protein attached to the outer mitochondrial membrane that signals downstream of RIG-I and MDA-5 to activate IRF3 and NFκB in response to viral infection. MBL-associated serine proteases See MASP-1, MASP-2, MASP-3. M cells Specialized epithelial cell type in the intestinal epithelium over Peyer’s patches, through which antigens and pathogens enter from the gut.


Immunology_Janeway

Immunology_Janeway. M cells Specialized epithelial cell type in the intestinal epithelium over Peyer’s patches, through which antigens and pathogens enter from the gut. MD-2 Accessory protein for TLR-4 activity. MDA-5 (melanoma differentiation-associated 5, also helicard) This protein contains an RNA helicase-like domain similar to RIG-I, and senses double-stranded RNA for detection of intracellular viral infections. medulla The central or collecting point of an organ. The thymic medulla is the central area of each thymic lobe, rich in bone marrow-derived antigen-presenting cells and the cells of a distinctive medullary epithelium. The medulla of the lymph node is a site of macrophage and plasma cell concentration through which the lymph ﬂows on its way to the efferent lymphatics. MEK1 A MAPK kinase in the Raf–MEK1–Erk signaling module, which is a part of a signaling pathway in lymphocytes leading to activation of the transcription factor AP-1.


Immunology_Janeway

Immunology_Janeway. MEK1 A MAPK kinase in the Raf–MEK1–Erk signaling module, which is a part of a signaling pathway in lymphocytes leading to activation of the transcription factor AP-1. melanoma-associated antigens (MAGE) Heterogeneous group of proteins of diverse or unknown functions characterized by restricted expression limited to tumors (i.e., melanoma) or testis germ cells. membrane associated ring finger (C3HC4) 1, MARCH-1 An E3 ligase expressed in B cells, dendritic cells, and macrophages that induces the constitutive degradation of MHC class II molecules, regulating their steady-state expression. membrane attack Effector pathway of complement based on formation of the membrane-attack complex (MAC). membrane-attack complex (MAC) Protein complex composed of C5b to C9 that assembles a membrane-spanning hydrophilic pore on pathogen surfaces, causing cell lysis.


Immunology_Janeway

Immunology_Janeway. membrane-attack complex (MAC) Protein complex composed of C5b to C9 that assembles a membrane-spanning hydrophilic pore on pathogen surfaces, causing cell lysis. membrane cofactor of proteolysis (MCP or CD46) A complement regulatory protein, a host-cell membrane protein that acts in conjunction with factor I to cleave C3b to its inactive derivative iC3b and thus prevent convertase formation. membrane immunoglobulin (mIg) Transmembrane immunoglobulin present on B cells; it is the B-cell receptor for antigen. memory B cells See memory cells. memory cells B and T lymphocytes that mediate immunological memory. They are more sensitive than naive lymphocytes to antigen and respond rapidly on reexposure to the antigen that originally induced them. mesenteric lymph nodes Lymph nodes located in the connective tissue (mesentery) that tethers the intestine to the rear wall of the abdomen. They drain the GALT.


Immunology_Janeway

Immunology_Janeway. mesenteric lymph nodes Lymph nodes located in the connective tissue (mesentery) that tethers the intestine to the rear wall of the abdomen. They drain the GALT. metastasis Spread of a tumor from its original location to distant organs of the body by traveling through the blood or lymphatics or by direct extension. 2ʹ-O-methyltransferase (MTase) An enzyme that transfers a methyl group to the 2ʹ hydroxyl of the first and second ribose groups in mRNA. Viruses that acquire MTase can produce cap-1 and cap-2 on their transcripts and thereby evade restriction by IFIT1. MF-59 A proprietary adjuvant based on squaline and water used in Europe and Canada in conjunction with inﬂuenza vaccine. MHC class I See MHC class I molecules. MHC class I deficiency An immunodeficiency disease in which MHC class I molecules are not present on the cell surface, usually as a result of an inherited deficiency of either TAP-1 or TAP-2.


Immunology_Janeway

Immunology_Janeway. MHC class I deficiency An immunodeficiency disease in which MHC class I molecules are not present on the cell surface, usually as a result of an inherited deficiency of either TAP-1 or TAP-2. MHC class I molecules Polymorphic cell-surface proteins encoded in the MHC locus and expressed on most cells. They present antigenic peptides generated in the cytosol to CD8 T cells, and also bind the co-receptor CD8. MHC class II See MHC class II molecules. MHC class II compartment (MIIC) The cellular vesicles in which MHC class II molecules accumulate, encounter HLA-DM, and bind antigenic peptides, before migrating to the surface of the cell. MHC class II deficiency A rare immunodeficiency disease in which MHC class II molecules are not present on cells as a result of various inherited defects. Patients are severely immunodeficient and have few CD4 T cells.


Immunology_Janeway

Immunology_Janeway. MHC class II molecules Polymorphic cell-surface proteins encoded in the MHC locus are expressed primarily on specialized antigen-presenting cells. They present antigenic peptides derived from internalized extracellular pathogens to CD4 T cells and also bind the co-receptor CD4. MHC class II transactivator (CIITA) Protein that activates transcription of MHC class II genes. Defects in the CIITA gene are one cause of MHC class II deficiency. MHC haplotype A set of alleles in the MHC that is inherited unchanged (that is, without recombination) from one parent. MHC molecules Highly polymorphic cell-surface proteins encoded by MHC class I and MHC class II genes involved in presentation of peptide antigens to T cells. They are also known as histocompatibility antigens. MHC restriction The fact that a peptide antigen can only be recognized by a given T cell if it is bound to a particular self MHC molecule. MHC restriction is a consequence of events that occur during T-cell development.


Immunology_Janeway

Immunology_Janeway. MIC-A, MIC-B MHC class Ib proteins that are induced by stress, infection, or transformation in many cell types and are recognized by NKG2D. microautophagy The continuous internalization of the cytosol into the vesicular system. microbial glycolipids Diverse class of antigens frequently presented by CD1 molecules to iNKT cells. microbiome See commensal microorganisms. microbiota See commensal microorganisms. microclusters Assemblies of small numbers of T-cell receptors that may be involved in the initiation of T-cell receptor activation by antigen in naive T cells. microfold cells See M cells. microglial cells An embryonically derived form of tissue macrophage in the central nervous system that is dependent on IL-34 for local self-renewal throughout life. minor histocompatibility antigens Peptides of polymorphic cellular proteins bound to MHC molecules that can lead to graft rejection when they are recognized by T cells.


Immunology_Janeway

Immunology_Janeway. minor histocompatibility antigens Peptides of polymorphic cellular proteins bound to MHC molecules that can lead to graft rejection when they are recognized by T cells. minor lymphocyte stimulating (Mls) antigens An old term referring to non-MHC antigens responsible for unusually strong T cell responses to cells from different strains of mice, now known to be superantigens encoded by endogenous retroviruses. mismatch repair A type of DNA repair that causes mutations and is involved in somatic hypermutation and class switching in B cells. missing self Refers to the loss of cell-surface molecules that engage with inhibitory receptors on NK cells, resulting in NK-cell activation.


Immunology_Janeway

Immunology_Janeway. missing self Refers to the loss of cell-surface molecules that engage with inhibitory receptors on NK cells, resulting in NK-cell activation. mitogen-activated protein kinases (MAPKs) A series of protein kinases that become phosphorylated and activated on cellular stimulation by a variety of ligands, and lead to new gene expression by phosphorylating key transcription factors. The MAPKs are part of many signaling pathways, especially those leading to cell proliferation, and have different names in different organisms. mixed essential cryoglobulinemia Disease due to the production of cryoglobulins (cold-precipitable immunoglobulins), sometimes in response to chronic infections such as hepatitis C, which can lead to the deposition of immune complexes in joints and tissues.


Immunology_Janeway

Immunology_Janeway. mixed lymphocyte reaction (MLR) A test for histocompatibility in which lymphocytes from donor and recipient are cultured together. If the two people are histoincompatible, the recipient’s T cells recognize the allogeneic MHC molecules on the cells of the other donor as ‘foreign’ and proliferate. molecular mimicry The similarity between some pathogen antigens and host antigens, such that antibodies and T cells produced against the former also react against host tissues. This similarity may be the cause of some autoimmunity. monoclonal antibodies Antibodies produced by a single clone of B lymphocytes, so that they are all identical. monocyte Type of white blood cell with a bean-shaped nucleus; it is a precursor of tissue macrophages. monomorphic Describes a gene that occurs in only one form. Cf. polymorphic.


Immunology_Janeway

Immunology_Janeway. monocyte Type of white blood cell with a bean-shaped nucleus; it is a precursor of tissue macrophages. monomorphic Describes a gene that occurs in only one form. Cf. polymorphic. motheaten A mutation in the SHP-1 protein phosphatase that impairs the function of some inhibitory receptors, such as Ly49, resulting in over-activation of various cells, including NK cells. Mice with this mutation have a 'motheaten' appearance due to chronic inﬂammation. MR1 A 'non-classical' MHC class Ib molecule that binds certain folic acid metabolites produced by bacteria for recognition by mucosal associated invariant T (MAIT) cells. MRE11A (meitotic recombination 11 homolog a) A protein involved in DNA damage and repair mechanisms that also recognizes cytoplasmic dsDNA and can activate the STING pathway. MSH2, MSH6 Mismatch repair proteins that detect uridine and recruit nucleases to remove the damaged and several adjacent nucleotides.


Immunology_Janeway

Immunology_Janeway. MSH2, MSH6 Mismatch repair proteins that detect uridine and recruit nucleases to remove the damaged and several adjacent nucleotides. mTOR (mammalian target of rapamycin) Serine/threonine kinase that functions in regulating numerous aspects of cell metabolism and function in complex with regulatory proteins Raptor or Rictor. The Raptor/mTOR complex (mTORC1) is inhibited by the immunosuppressive drug rapamycin. mTORC1, mTORC2 Active complexes of mTOR formed with the regulatory proteins Raptor and Rictor, respectively. mucins Highly glycosylated cell-surface proteins. Mucin-like molecules are bound by L-selectin in lymphocyte homing. Muckle–Wells syndrome An inherited episodic autoinﬂammatory disease caused by mutations in the gene encoding NLRP3, a component of the inﬂammasome.


Immunology_Janeway

Immunology_Janeway. Muckle–Wells syndrome An inherited episodic autoinﬂammatory disease caused by mutations in the gene encoding NLRP3, a component of the inﬂammasome. mucosal associated invariant T cells (MAIT) Primarily γ:δT cells with limited diversity present in the mucosal immune system that respond to bacterially derived folate derivates presented by the nonclassical MHC class Ib molecule MR1. mucosa-associated lymphoid tissue (MALT) Generic term for all organized lymphoid tissue found at mucosal surfaces, in which an adaptive immune response can be initiated. It comprises GALT, NALT, and BALT (when present). mucosal epithelia Mucus-coated epithelia lining the body’s internal cavities that connect with the outside (such as the gut, airways, and vaginal tract).


Immunology_Janeway

Immunology_Janeway. mucosal epithelia Mucus-coated epithelia lining the body’s internal cavities that connect with the outside (such as the gut, airways, and vaginal tract). mucosal immune system The immune system that protects internal mucosal surfaces (such as the linings of the gut, respiratory tract, and urogenital tracts), which are the site of entry for virtually all pathogens and other antigens. See also mucosa-associated lymphoid tissue. mucosal mast cells Specialized mast cells present in mucosa. They produce little histamine but large amounts of prostaglandins and leukotrienes. mucosal tolerance The suppression of specific systemic immune responses to an antigen by the previous administration of the same antigen by a mucosal route. mucus Sticky solution of proteins (mucins) secreted by goblet cells of internal epithelia, forming a protective layer on the epithelial surface.


Immunology_Janeway

Immunology_Janeway. mucus Sticky solution of proteins (mucins) secreted by goblet cells of internal epithelia, forming a protective layer on the epithelial surface. multiple sclerosis A neurological autoimmune disease characterized by focal demyelination in the central nervous system, lymphocytic infiltration in the brain, and a chronic progressive course. multipotent progenitor cells (MPPs) Bone marrow cells that can give rise to both lymphoid and myeloid cells but are no longer self-renewing stem cells. muramyl dipeptide (MDP) A component of the peptidoglycan of most bacteria that is recognized by the intracellular sensor NOD2. muromomab A mouse antibody against human CD3 used to treat transplant rejection; this was the first monoclonal antibody approved as a drug in humans. mutualism A symbiotic relationship between two organisms in which both benefit, such as the relationship between a human and its normal resident (commensal) gut microorganisms.


Immunology_Janeway

Immunology_Janeway. mutualism A symbiotic relationship between two organisms in which both benefit, such as the relationship between a human and its normal resident (commensal) gut microorganisms. Mx (myxoma resistant) proteins Interferon-inducible proteins required for cellular resistance to inﬂuenza virus replication. myasthenia gravis An autoimmune disease in which autoantibodies against the acetylcholine receptor on skeletal muscle cells cause a block in neuromuscular junctions, leading to progressive weakness and eventually death. mycophenolate An inhibitor of the synthesis of guanosine monophosphate that acts as a cytotoxic immunosuppressive drug. It acts by killing rapidly dividing cells, including lymphocytes proliferating in response to antigen. mycophenolate mofetil Pro-drug used in cancer treatment that is metabolized to mycophenolate, and inhibitor of inosine monophosphate dehydrogenase, thereby impairing guanosine monophosphate, and thus DNA, synthesis.


Immunology_Janeway

Immunology_Janeway. MyD88 An adaptor protein that functions in signaling by all TLR proteins except TLR3. myeloid Refers to the lineage of blood cells that includes all leukocytes except lymphocytes. myeloid-derived suppressor cells (MDSCs) Cells in tumors that can inhibit T-cell activation within the tumor. myelomonocytic series Innate immune cells derived from myelomonocytic bone marrow precursors, including neutrophils, basophils, eosinophils, monocytes, and dendritic cells. NADPH oxidase Multicomponent enzyme complex that is assembled and activated in the phagolysosome membrane in stimulated phagocytes. It generates superoxide in an oxygen-requiring reaction called the respiratory burst. NAIP2 An NLR protein that, together with NLRC4, recognizes the PrgJ protein of the Salmonella typhimurium type III injection system to activate an inﬂammasome pathway in response to infection.


Immunology_Janeway

Immunology_Janeway. NAIP2 An NLR protein that, together with NLRC4, recognizes the PrgJ protein of the Salmonella typhimurium type III injection system to activate an inﬂammasome pathway in response to infection. NAIP5 An NLR protein that, together with NLRC4, recognizes intracellular ﬂagellin to activate an inﬂammasome pathway in response to infection. naive lymphocytes T cells or B cells that have undergone normal development in the thymus or the bone marrow but have not yet been activated by foreign (or self) antigens. naive T cells Lymphocytes that have never encountered their specific antigen and thus have never responded to it, as distinct from effector and memory lymphocytes.


Immunology_Janeway

Immunology_Janeway. naive T cells Lymphocytes that have never encountered their specific antigen and thus have never responded to it, as distinct from effector and memory lymphocytes. nasal-associated lymphoid tissue (NALT) Organized lymphoid tissues found in the upper respiratory tract. In humans, NALT consists of Waldeyer’s ring, which includes the adenoids, palatine, and lingual tonsils, plus other similarly organized lymphoid tissue located around the pharynx. It is part of the mucosal immune system. natalizumab Humanized antibody to α4 integrin used to treat Crohn's disease and multiple sclerosis. It blocks lymphocytes' adhesion to endothelium, impairing their migration into tissues. natural antibodies Antibodies produced by the immune system in the apparent absence of any infection. They have a broad specificity for self and microbial antigens, can react with many pathogens, and can activate complement.


Immunology_Janeway

Immunology_Janeway. natural cytotoxicity receptors (NCRs) Activating receptors on NK cells that recognize infected cells and stimulate cell killing by the NK cell. natural interferon-producing cells See plasmacytoid dendritic cells. natural killer (NK) cell A type of ILC that is important in innate immunity to viruses and other intracellular pathogens, and in antibody-dependent cell-mediated cytotoxicity (ADCC). NK cells express activating and inhibitory receptors, but not the antigen-specific receptors of T or B cells. necrosis The process of cell death that occurs in response to noxious stimuli, such as nutrient deprivation, physical injury, or infection. To be distinguished from apoptosis, in which the cell activates an internal, or intrinsic, program of death, such as occurs in immune cells as a result of deficiency of cell survival signals.


Immunology_Janeway

Immunology_Janeway. negative selection The process by which self-reactive thymocytes are deleted from the repertoire during T-cell development in the thymus. Autoreactive B cells undergo a similar process in bone marrow. NEMO See IKK. NEMO deficiency See X-linked hypohidrotic ectodermal dysplasia and immunodeficiency. neoepitopes Type of tumor rejection antigen created by mutations in protein that can be presented by self-MHC molecules to T cells. neonatal Fc receptor (FcRn) See FcRn. neuraminidase An inﬂuenza virus protein that cleaves sialic acid from host cells to allow viral detachment, a common antigenic determinant, and target of antiviral neuraminidase inhibitors. neutralization Inhibition of the infectivity of a virus or the toxicity of a toxin molecule by the binding of antibodies. neutralizing antibodies Antibodies that inhibit the infectivity of a virus or the toxicity of a toxin. neutropenia Abnormally low levels of neutrophils in the blood.


Immunology_Janeway

Immunology_Janeway. neutralizing antibodies Antibodies that inhibit the infectivity of a virus or the toxicity of a toxin. neutropenia Abnormally low levels of neutrophils in the blood. neutrophil The most numerous type of white blood cell in human peripheral blood. Neutrophils are phagocytic cells with a multilobed nucleus and granules that stain with neutral stains. They enter infected tissues and engulf and kill extracellular pathogens. neutrophil elastase Proteolytic enzyme stored in the granules of neutrophils that is involved in the processing of antimicrobial peptides. neutrophil extracellular traps (NETs) A meshwork of nuclear chromatin that is released into the extracellular space by neutrophils undergoing apoptosis at sites of infection, serving as a scaffold that traps extracellular bacteria to enhance their phagocytosis by other phagocytes.


Immunology_Janeway

Immunology_Janeway. NFκB A heterodimeric transcription factor activated by the stimulation of Toll-like receptors and also by antigen receptor signaling composed of p50 and p65 subunits. NFAT See nuclear factor of activated T cells. Nfil3 A transcription factor important during the development of several types of immune cells including certain types of NK cells. NHEJ See nonhomologous end joining. nitric oxide A reactive molecular gas species produced by cells— particularly macrophages—during infection, that is toxic to bacteria and intracellular microbes. nivolumab Human anti-PD-1 antibody used for checkpoint blockade in treatment of metastatic melanoma. NK receptor complex (NKC) A cluster of genes that encode a family of receptors on NK cells. NKG2 Family of C-type lectins that supply one of the subunits of KLR-family receptors on NK cells. NKG2D Activating C-type lectin receptor on NK cells, cytotoxic T cells, and γ:δT cells that recognizes the stress-response proteins MIC-A and MIC-B.


Immunology_Janeway

Immunology_Janeway. NKG2D Activating C-type lectin receptor on NK cells, cytotoxic T cells, and γ:δT cells that recognizes the stress-response proteins MIC-A and MIC-B. NLRC4 An NLR family member that cooperates with NAIP2 and NAIP5. NLRP family A group of 14 NOD-like receptor (NLR) proteins that contain a pyrin domain and function in the formation of a signaling complex called the inﬂammasome. NLRP3 A member of the family of intracellular NOD-like receptor proteins that have pyrin domains. It acts as a sensor of cellular damage and is part of the inﬂammasome. Sometimes called NALP3. N-nucleotides Nontemplated nucleotides inserted by the enzyme terminal deoxynucleotidyl transferase into the junctions between gene segments of T-cell receptor and immunoglobulin heavy-chain V regions during gene segment joining. Translation of these N-regions markedly increases the diversity of these receptor chains.


Immunology_Janeway

Immunology_Janeway. NOD subfamily A subgroup of NLR proteins that contain a CARD domain which is used for activation of downstream signaling. NOD1, NOD2 Intracellular proteins of the NOD subfamily that contain a leucine-rich repeat (LRR) domain that binds components of bacterial cell walls to activate the NFκB pathway and initiate inﬂammatory responses. NOD-like receptors (NLRs) Large family of proteins containing a nucleotide-oligomerization domain (NOD) associated with various other domains, and whose general function is the detection of microbes and of cellular stress. nonamer Conserved nine-nucleotide DNA sequence in the recombination signal sequences (RSSs) ﬂanking gene segments in the immunoglobulin and T-cell receptor loci. non-canonical inflammasome An alternate form of the inﬂammasome that is independent of caspase 1, but instead relies on caspase 11 (mice) or caspases 4 or 5 (human).


Immunology_Janeway

Immunology_Janeway. non-canonical inflammasome An alternate form of the inﬂammasome that is independent of caspase 1, but instead relies on caspase 11 (mice) or caspases 4 or 5 (human). non-canonical NFκB pathway A pathway for NFκB activation that is distinct from the one activated by antigen receptor stimulation. This pathway leads to activation of the NFκB-inducing kinase, NIK, which phosphorylates and activates IκB kinase α (IKKα) inducing cleavage of the NFκB precursor protein p100 to form the active p52 subunit. nonclassical MHC class Ib genes A class of proteins encoded within the MHC that are related to the MHC class I molecules but are not highly polymorphic and present a restricted set of antigens. non-depleting antibodies Immunosuppressive antibodies that block the function of target proteins on cells without causing the cells to be destroyed. nonhomologous end joining (NHEJ) DNA repair pathway that directly ligates double-stranded DNA breaks without use of a homologous template.


Immunology_Janeway

Immunology_Janeway. nonhomologous end joining (NHEJ) DNA repair pathway that directly ligates double-stranded DNA breaks without use of a homologous template. nonproductive rearrangements Rearrangements of T-cell receptor or immunoglobulin gene segments that cannot encode a protein because the coding sequences are in the wrong translational reading frame. nonreceptor kinase Cytoplasmic protein kinases that associate with the intracellular tails of signaling receptors and help generate the signal but are not an intrinsic part of the receptor itself. non-structural protein 1 (NS1) An inﬂuenza A virus protein that inhibits TRIM25, an intermediate signaling protein downstream of the viral sensors RIG-I and MDA-5, thereby promoting evasion of innate immunity. nuclear factor of activated T cells A family of transcription factors that are activated in response to increased cytoplasmic calcium following antigen receptor signaling in lymphocytes.


Immunology_Janeway

Immunology_Janeway. nuclear factor of activated T cells A family of transcription factors that are activated in response to increased cytoplasmic calcium following antigen receptor signaling in lymphocytes. nucleotide-binding oligomerization domain (NOD) A type of conserved domain originally recognized in ATP-binding cassette (ABC) transporters present present in a large number of proteins, but which also mediates protein homooligomerization. nude A mutation in mice that results in hairlessness and defective formation of the thymic stroma, so that mice homozygous for this mutation have no mature T cells. NY-ESO-1 A particular highly immunogenic cancer-testis antigen expressed by many types of human tumors including melanoma. occupational allergies An allergic reaction induced to an allergen to which someone is habitually exposed in their work.


Immunology_Janeway

Immunology_Janeway. occupational allergies An allergic reaction induced to an allergen to which someone is habitually exposed in their work. oligoadenylate synthetase Enzyme produced in response to stimulation of cells by interferon. It synthesizes unusual nucleotide polymers, which in turn activate a ribonuclease that degrades viral RNA. Omenn syndrome A severe immunodeficiency disease characterized by defects in either of the RAG genes. Affected individuals make small amounts of functional RAG protein, allowing a small amount of V(D)J recombination. opsonization The coating of the surface of a pathogen by antibody and/or complement that makes it more easily ingested by phagocytes. oral tolerance The suppression of specific systemic immune responses to an antigen by the prior administration of the same antigen by the oral (enteric) route.


Immunology_Janeway

Immunology_Janeway. oral tolerance The suppression of specific systemic immune responses to an antigen by the prior administration of the same antigen by the oral (enteric) route. original antigenic sin The tendency of humans to make antibody responses to those epitopes shared between the first strain of a virus they encounter and subsequent related viruses, while ignoring other highly immunogenic epitopes on the second and subsequent viruses. p50 See NFκB. p65 See NFκB. PA28 proteasome-activator complex A multisubunit protein complex induced by interferon-γ that takes the place of the 19S regulatory cap of the proteasome and increases the rate of peptides exiting from the proteasome catalytic core. palatine tonsils Paired masses of organized peripheral lymphoid tissues located on each side of the throat, and in which an adaptive immune response can be generated. They are part of the mucosal immune system.


Immunology_Janeway

Immunology_Janeway. Paneth cells Specialized epithelial cells at the base of the crypts in the small intestine that secrete antimicrobial peptides. papain A protease that cleaves the IgG antibody molecule on the amino-terminal side of disulfide linkages, producing two Fab fragments and one Fc fragment. paracortical areas The T-cell area of lymph nodes. paracrine Describes a cytokine or other biologically active molecule acting on cells near to those that produce it. parasites Organisms that obtain sustenance from a live host. In immunology, it refers to worms and protozoa, the subject matter of parasitology. paroxysmal nocturnal hemoglobinuria A disease in which complement regulatory proteins are defective, so that activation of complement binding to red blood cells leads to episodes of spontaneous hemolysis. passive immunization The injection of antibody or immune serum into a naive recipient to provide specific immunological protection. Cf. active immunization.


Immunology_Janeway

Immunology_Janeway. passive immunization The injection of antibody or immune serum into a naive recipient to provide specific immunological protection. Cf. active immunization. pathogen Microorganism that typically causes disease when it infects a host. pathogen-associated molecular patterns (PAMPs) Molecules specifically associated with groups of pathogens that are recognized by cells of the innate immune system. pathogenesis The origin or cause of the pathology of a disease. pathogenic microorganisms Microorganism that typically causes disease when it infects a host. patrolling monocyte A form of circulating monocyte that adheres to and surveys the vascular endothelium, distinguished from classical monocytes by its low expression of Ly6C. pattern recognition receptors (PRRs) Receptors of the innate immune system that recognize common molecular patterns on pathogen surfaces.


Immunology_Janeway

Immunology_Janeway. pattern recognition receptors (PRRs) Receptors of the innate immune system that recognize common molecular patterns on pathogen surfaces. PD-1 Programmed death-1, a receptor on T cells that when bound by its ligands, PD-L1 and PD-L2, inhibits signaling from the antigen receptor. PD-1 contains an ITIM motif in its cytoplasmic tail. Target of cancer therapies aimed at stimulating T-cell responses to tumors. PD-L1 (programmed death ligand-1, B7-H1) Transmembrane receptor that binds to the inhibitory receptor PD-1. PD-L1 is expressed on many cell types and is upregulated by inﬂammatory cytokines. PD-L2 (programmed death ligand-2, B7-DC) Transmembrane receptor that binds to the inhibitory receptor PD-1; mainly expressed on dendritic cells. PECAM See CD31. pembrolizumab Human anti-PD-1 antibody used for checkpoint blockade in treatment of metastatic melanoma. pemphigus vulgaris An autoimmune disease characterized by severe blistering of the skin and mucosal membranes.


Immunology_Janeway

Immunology_Janeway. pemphigus vulgaris An autoimmune disease characterized by severe blistering of the skin and mucosal membranes. pentameric IgM Major form of the IgM antibodies produced by the action of J chain resulting in higher avidity for antigens. pentraxin A family of acute-phase proteins formed of five identical subunits, to which C-reactive protein and serum amyloid protein belong. pepsin A protease that cleaves several sites on the carboxy-terminal side of the disulfide linkages, producing the F(abʹ)2 fragment and several fragments of the Fc region. peptide-binding cleft The longitudinal cleft in the top surface of an MHC molecule into which the antigenic peptide is bound. Sometimes called the peptide-binding groove. peptide editing In the context of antigen processing and presentation, the removal of unstably bound peptides from MHC class II molecules by HLA-DM.


Immunology_Janeway

Immunology_Janeway. peptide editing In the context of antigen processing and presentation, the removal of unstably bound peptides from MHC class II molecules by HLA-DM. peptide-loading complex (PLC) A protein complex in the endoplasmic reticulum that loads peptides onto MHC class I molecules. peptide:MHC tetramers Four specific peptide:MHC complexes bound to a single molecule of ﬂuorescently labeled streptavidin, which are used to identify populations of antigen-specific T cells. peptidoglycan A component of bacterial cell walls that is recognized by certain receptors of the innate immune system. peptidoglycan-recognition proteins (PGRPs) A family of Drosophila proteins that bind peptidoglycans from bacterial cell walls that serve to initiate the proteolytic cascade of the TOLL pathway. periarteriolar lymphoid sheath (PALS) Part of the inner region of the white pulp of the spleen; it contains mainly T cells.


Immunology_Janeway

Immunology_Janeway. periarteriolar lymphoid sheath (PALS) Part of the inner region of the white pulp of the spleen; it contains mainly T cells. peripheral lymphoid organs, peripheral lymphoid tissues The lymph nodes, spleen, and mucosa-associated lymphoid tissues, in which adaptive immune responses are induced, as opposed to the central lymphoid organs, in which lymphocytes develop. They are also called secondary lymphoid organs and tissues. peripheral tolerance Tolerance acquired by mature lymphocytes in the peripheral tissues, as opposed to central tolerance, which is acquired by immature lymphocytes during their development. Peyer’s patches Organized peripheral lymphoid organs under the epithelium in the small intestine, especially the ileum, and in which an adaptive immune response can be initiated. They contain lymphoid follicles and T-cell areas. They are part of the gut-associated lymphoid tissues (GALT). phagocyte oxidase See NADPH oxidase. phagocytic glycoprotein-1 (Pgp1) See CD44.


Immunology_Janeway

Immunology_Janeway. phagocyte oxidase See NADPH oxidase. phagocytic glycoprotein-1 (Pgp1) See CD44. phagocytosis The internalization of particulate matter by cells by a process of engulfment, in which the cell membrane surrounds the material, eventually forming an intracellular vesicle (phagosome) containing the ingested material. phagolysosome Intracellular vesicle formed by the fusion of a phagosome (containing ingested material) and a lysosome, and in which the ingested material is broken down. phagophore A crescent-shaped double-membrane cytoplasmic structure. phagosome Intracellular vesicle formed when particulate material is ingested by a phagocyte. phosphatidylinositol 3-kinase (PI 3-kinase) Enzyme involved in intracellular signaling pathways. It phosphorylates the membrane lipid phosphatidylinositol 3,4-bisphosphate (PIP2) to form phosphatidylinositol 3,4,5-trisphosphate (PIP3), which can recruit signaling proteins containing pleckstrin homology (PH) domains to the membrane.


Immunology_Janeway

Immunology_Janeway. phosphatidylinositol kinases Enzymes that phosphorylate the inositol headgroup on membrane lipids to produce phosphorylated derivatives that have a variety of functions in intracellular signaling. phospholipase C-γ (PLC-γ) Key enzyme in intracellular signaling pathways leading from many different receptors. It is activated by membrane recruitment and tyrosine phosphorylation following receptor ligation, and cleaves membrane inositol phospholipids into inositol trisphosphate and diacylglycerol. phosphorylation Addition of a phosphate group to a molecule, usually a protein, catalyzed by enzymes called kinases. phycoerythrin A light harvesting protein pigment made by algae and used in conjunction with ﬂow cytometry, it can also be recognized as a ligand by some γ:δ T-cell receptors.


Immunology_Janeway

Immunology_Janeway. phycoerythrin A light harvesting protein pigment made by algae and used in conjunction with ﬂow cytometry, it can also be recognized as a ligand by some γ:δ T-cell receptors. physiological inflammation The state of the normal healthy intestine, whose wall contains large numbers of effector lymphocytes and other cells. It is thought to be the result of continual stimulation by commensal organisms and food antigens. pi-cation interactions Chemical interaction between a cation (e.g., Na+) and the pi-electron system of an aromatic moiety. pilin An adhesin of Neisseria gonorrhoeae allowing attachment to and infection of epithelial cells of urinary and reproductive tracts. PIP2 Phosphatidylinositol 3,4-bisphosphate, a membrane-associated phospholipid that is cleaved by phospholipase C-γ to give the signaling molecules diacylglycerol and inositol trisphosphate and is phosphorylated by PI3-kinase to generate PIP3.


Immunology_Janeway

Immunology_Janeway. PIP3 Phosphatidylinositol 3,4,5-trisphosphate, a membrane-associated phospholipid that can recruit intracellular signaling molecules containing pleckstrin homology (PH) domains to the membrane. PKR Serine/threonine kinase activated by IFN-α and IFN-β. It phosphorylates the eukaryotic protein synthesis initiation factor eIF-2, inhibiting translation and thus contributing to the inhibition of viral replication. plasma cells Terminally differentiated activated B lymphocytes. Plasma cells are the main antibody-secreting cells of the body. They are found in the medulla of the lymph nodes, in splenic red pulp, in bone marrow, and in mucosal tissues. plasmablasts A B cell in a lymph node that already shows some features of a plasma cell. plasmacytoid dendritic cells (pDCs) A distinct lineage of dendritic cells that secrete large amounts of interferon on activation by pathogens and their products via receptors such as Toll-like receptors. Cf. conventional dendritic cells.


Immunology_Janeway

Immunology_Janeway. platelet-activating factor (PAF) A lipid mediator that activates the blood clotting cascade and several other components of the innate immune system. pluripotent Typically referring to the capacity of a progenitor cell to generate all possible lineages of an organ system. P-nucleotides Short palindromic nucleotide sequences formed between gene segments of the rearranged V-region gene generated by the asymmetric opening of the hairpin intermediate during RAG-mediated rearrangement. Polη An error-prone, 'translesion', DNA polymerase involved in repairing DNA damage caused by UV radiation and in somatic hypermutation. polyclonal activation The activation of lymphocytes by a mitogen regardless of antigen specificity, leading to the activation of clones of lymphocytes of multiple antigen specificities. polygenic Containing several separate loci encoding proteins of identical function; applied to the MHC. Cf. polymorphic.


Immunology_Janeway

Immunology_Janeway. polygenic Containing several separate loci encoding proteins of identical function; applied to the MHC. Cf. polymorphic. polymerase stalling The halting of RNA polymerase during the transcription of a gene at locations within the gene locus, known to be a regulated process, and involved in mechanisms of isotype switching. polymeric immunoglobulin receptor (pIgR) The receptor for polymeric immunoglobulins IgA and IgM on basolateral surfaces of mucosal and glandular epithelial cells that transports IgA (or IgM) into secretions. polymorphic Existing in a variety of different forms; applied to a gene, occurring in a variety of different alleles. polymorphism Applied to genes, variability at a gene locus in which all variants occur at a frequency greater than 1%. polymorphonuclear leukocytes See granulocytes.


Immunology_Janeway

Immunology_Janeway. polymorphism Applied to genes, variability at a gene locus in which all variants occur at a frequency greater than 1%. polymorphonuclear leukocytes See granulocytes. polysaccharide capsules A distinct structure in some bacteria—both Gram-negative and Gram-positive—that lies outside cell membrane and cell wall that can prevent direct phagocytosis by macrophages without the aid of antibody or complement. polyubiquitin chains Polymers of ubiquitin covalently linked from lysine residues within one ubiquitin monomer to the carboxy terminus of a second ubiquitin. PorA Outer membrane protein of Neisseria meningitidis that binds C4BP, thereby inactivating C3b deposited on its surface. positive selection A process occurring in the thymus in which only those developing T cells whose receptors can recognize antigens presented by self MHC molecules can mature.


Immunology_Janeway

Immunology_Janeway. positive selection A process occurring in the thymus in which only those developing T cells whose receptors can recognize antigens presented by self MHC molecules can mature. post-transplant lymphoproliferative disorder B-cell expansion driven by Epstein–Barr virus (EBV) in which the B cells can undergo mutations and become malignant. This can occur when patients are immunosuppressed after, for example, solid organ transplantation. pre-B-cell receptor Receptor produced by pre-B cells that includes an immunoglobulin heavy chain, as well as surrogate light-chain proteins, Igα and Igβ signaling subnits. Signaling through this receptor induces the pre-B cell to enter the cell cycle, to turn off the RAG genes, to degrade the RAG proteins, and to expand by several cell divisions.


Immunology_Janeway

Immunology_Janeway. pre-T-cell receptor Receptor protein produced by developing T lymphocytes at the pre-T-cell stage. It is composed of TCRβ chains that pair with a surrogate α chain called pTα (pre-T-cell α), and is associated with the CD3 signaling chains. Signaling through this receptor induces pre-T-cell proliferation, expression of CD4 and CD8, and cessation of TCR β chain rearrangement. prednisone A synthetic steroid with potent anti-inﬂammatory and immunosuppressive activity used in treating acute graft rejection, autoimmune disease, and lymphoid tumors. PREX1 A guanine exchange factor (GEF) activated downstream of small G proteins in response to activation of GPCRs such as the fMLP or C5a receptor. PrgJ A protein component of the Salmonella typhimurium type III secretion system inner rod used by the bacterium to infect eukaryotic cells. This protein is detected by NLR proteins NAIP2 and NLRC4.


Immunology_Janeway

Immunology_Janeway. PrgJ A protein component of the Salmonella typhimurium type III secretion system inner rod used by the bacterium to infect eukaryotic cells. This protein is detected by NLR proteins NAIP2 and NLRC4. primary focus Site of early antibody production by plasmablasts in medullary cords of lymph nodes that precedes the germinal center reaction and differentiation of plasma cells. primary granules Granules in neutrophils that correspond to lysosomes and contain antimicrobial peptides such as defensins and other antimicrobial agents. primary immune response The adaptive immune response that follows the first exposure to a particular antigen. primary immunization See priming. primary immunodeficiencies A lack of immune function that is caused by a genetic defect. primary lymphoid follicles Aggregates of resting B lymphocytes in peripheral lymphoid organs. Cf. secondary lymphoid follicle. primary lymphoid organs See central lymphoid organs.


Immunology_Janeway

Immunology_Janeway. primary lymphoid follicles Aggregates of resting B lymphocytes in peripheral lymphoid organs. Cf. secondary lymphoid follicle. primary lymphoid organs See central lymphoid organs. priming The first encounter with a given antigen, which generates the primary adaptive immune response. pro-B cells A stage in B-lymphocyte development in which cells have displayed B-cell surface marker proteins but have not yet completed heavy-chain gene rearrangement. pro-caspase 1 The inactive pro-form of caspase 1 that is part of the NLRP3 inﬂammasome. pro-inflammatory Tending to induce inﬂammation. profilin An actin-binding protein that sequesters monomeric actin. Protozoan profilins contain sequences recognized by TLR-11 and TLR-12. programmed cell death See apoptosis. progressive multifocal leukoencephalopathy (PML) Disease in immunocompromised patients caused by opportunisitic infection by JC virus, for example as a consequence of immunotherapy.


Immunology_Janeway

Immunology_Janeway. progressive multifocal leukoencephalopathy (PML) Disease in immunocompromised patients caused by opportunisitic infection by JC virus, for example as a consequence of immunotherapy. propeptides Inactive precursor form of a polypeptide or peptide, which requires proteolytic processing to produce the active peptide. properdin See factor P. prostaglandins Lipid products of the metabolism of arachidonic acid that have a variety of effects on tissues, including activities as inﬂammatory mediators. prostatic acid phosphatase (PAP) Enzyme expressed by prostate cancer cells used as tumor rejection antigen in the vaccine Sipuleucel-T (Provenge). proteasome A large intracellular multisubunit protease that degrades proteins, producing peptides. protein inhibitors of activated STAT (PIAS) A small family of proteins that inhibit STAT family transcription factors.


Immunology_Janeway

Immunology_Janeway. protein inhibitors of activated STAT (PIAS) A small family of proteins that inhibit STAT family transcription factors. protein-interaction domains, protein-interaction modules Protein domains, usually with no enzymatic activity themselves, that have binding specificity for particular sites (such as phosphorylated tyrosines, proline-rich regions, or membrane phospholipids) on other proteins or cellular structures. protein kinase C-θ (PKC-θ) A serine/threonine kinase that is activated by diacylglycerol as part of the signaling pathways from the antigen receptor in lymphocytes. protein kinases Enzymes that add phosphate groups to proteins at particular amino acid residues: tyrosine, threonine, or serine. protein phosphatases Enzymes that remove phosphate groups from proteins phosphorylated on tyrosine, threonine, or serine residues by protein kinases. proteolytic subunits β1, β2, β5 Constitutive components of the proteasome's catalytic chamber.


Immunology_Janeway

Immunology_Janeway. proteolytic subunits β1, β2, β5 Constitutive components of the proteasome's catalytic chamber. provirus The DNA form of a retrovirus when it is integrated into the host-cell genome, where it can remain transcriptionally inactive for long periods. P-selectin See selectins. P-selectin glycoprotein ligand-1 (PSGL-1) Protein expressed by activated effector T cells that is a ligand for P-selectin on endothelial cells, and may enable activated T cells to enter all tissues in small numbers. pseudo-dimeric peptide:MHC complexes Hypothetical complexes containing one antigen peptide:MHC molecule and one self peptide:MHC molecule on the surface of the antigen-presenting cell, which have been proposed to initiate T-cell activation. pseudogenes Gene elements that have lost the ability to encode a functional protein but that are retained in the genome and may continue to be transcribed normally.


Immunology_Janeway

Immunology_Janeway. pseudogenes Gene elements that have lost the ability to encode a functional protein but that are retained in the genome and may continue to be transcribed normally. psoriasis Chronic autoimmune disease thought to be driven by T cells manifested in skin, but which can also involve nails and joints (psoriatic arthropathy). psoriatic arthropathy See psoriasis. pTα See pre-T-cell receptor. purine nucleotide phosphorylase (PNP) deficiency An enzyme defect that results in severe combined immunodeficiency. The deficiency of PNP causes an intracellular accumulation of purine nucleosides, which are toxic to developing T cells. purinergic receptor P2X7 An ATP-activated ion channel that allows potassium efﬂux from cells when activated, which can trigger inﬂammasome activation in response to excessive extracellular ATP.


Immunology_Janeway

Immunology_Janeway. purinergic receptor P2X7 An ATP-activated ion channel that allows potassium efﬂux from cells when activated, which can trigger inﬂammasome activation in response to excessive extracellular ATP. pus Thick yellowish-white liquid typically found at sites of infection with some types of extracellular bacteria, which is composed of the remains of dead neutrophils and other cells. pus-forming bacteria Capsulated bacteria that result in pus formation at the site of infection. Also called pyogenic (pus-forming) bacteria. PYHIN A family of four intracellular sensor proteins containing an H inversion (HIN) domain in place of the LRR domain found in most other NLR proteins. The HIN domain functions in recognition of cytoplasmic dsDNA. Examples are AIM2 and IFI16. pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) Autoinﬂammatory syndrome that is caused by mutations in a protein that interacts with pyrin. pyogenic bacteria See pus-forming bacteria.


Immunology_Janeway

Immunology_Janeway. pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) Autoinﬂammatory syndrome that is caused by mutations in a protein that interacts with pyrin. pyogenic bacteria See pus-forming bacteria. pyrin One of several protein interaction domains, structurally related to but distinct from CARD, TIR, DD, and DED domains. pyroptosis A form of programmed cell death that is associated with abundant pro-inﬂammatory cytokines such as IL-1β and IL-18 produced through inﬂammasome activation. Qa-1 determinant modifiers (Qdm) A class of peptides derived from the leader peptides of various HLA class I molecules that can be bound by the human HLA-E and murine Qa-1 proteins, and then are recognized by the inhibitory NKG2A:CD94 receptor. quasi-species The different genetic forms of certain RNA viruses that are formed by mutation during the course of an infection. Rac See Rho family small GTPase proteins.


Immunology_Janeway

Immunology_Janeway. quasi-species The different genetic forms of certain RNA viruses that are formed by mutation during the course of an infection. Rac See Rho family small GTPase proteins. radiation-sensitive SCID (RS-SCID) Severe combined immunodeficiency due to a defect in DNA repair pathways, which renders cells unable to perform V(D)J recombination and unable to repair radiation-induced double-strand breaks. RAE1 (retinoic acid early inducible 1) protein family Several murine MHC class Ib proteins; these are orthologs of human RAET1 family proteins, including H60 and MULT1, and are ligands for murine NKG2D. RAET1 A family of 10 MHC class Ib proteins that are ligands for NKG2D, and includes several UL16-binding proteins (ULBPs). Raf A protein kinase in the Raf–MEK1–Erk signaling cascade that is the first protein kinase in the pathway, and is activated by the small GTPase Ras.


Immunology_Janeway

Immunology_Janeway. Raf A protein kinase in the Raf–MEK1–Erk signaling cascade that is the first protein kinase in the pathway, and is activated by the small GTPase Ras. RAG-1, RAG-2 Proteins encoded by the recombination-activating genes RAG-1 and RAG-2, which form a dimer that initiates V(D)J recombination. rapamycin An immunosuppressant drug that blocks intracellular signaling pathways involving the serine/threonine kinase mammalian target of rapamycin (mTOR) required for the inhibition of apoptosis and T-cell expansion. Also called sirolimus. Raptor See mTORC1. Ras A small GTPase with important roles in intracellular signaling pathways, including those from lymphocyte antigen receptors. reactive oxygen species (ROS) Superoxide anion (O2–) and hydrogen peroxide (H2O2), produced by phagocytic cells such as neutrophils and macrophages after ingestion of microbes, and which help kill the ingested microbes.


Immunology_Janeway

Immunology_Janeway. rearrangement by inversion In V(D)J recombination, the rearrangement of gene segments having RSS elements in an opposing orientation, leading to retention. receptor editing The replacement of a light or heavy chain of a self-reactive antigen receptor on immature B cells with a newly rearranged chain that does not confer autoreactivity. receptor-mediated endocytosis The internalization into endosomes of molecules bound to cell-surface receptors. receptor serine/threonine kinases Receptors that have an intrinsic serine/threonine kinase activity in their cytoplasmic tails. receptor tyrosine kinases Receptors that have an intrinsic tyrosine kinase activity in their cytoplasmic tails. recombination signal sequences (RSSs) DNA sequences at one or both ends of V, D, and J gene segments that are recognized by the RAG-1:RAG-2 recombinase. They consist of a conserved heptamer and nonamer element separated by 12 or 23 base pairs.


Immunology_Janeway

Immunology_Janeway. red pulp The nonlymphoid area of the spleen in which red blood cells are broken down. RegIIIγ An antimicrobial protein of the C-type lectin family, produced by Paneth cells in the gut in mice. regulatory T cells Effector CD4 T cells that inhibit T-cell responses and are involved in controlling immune reactions and preventing autoimmunity. Several different subsets have been distinguished, notably the natural regulatory T-cell lineage that is produced in the thymus, and the induced regulatory T cells that differentiate from naive CD4 T cells in the periphery in certain cytokine environments. regulatory tolerance Tolerance due to the actions of regulatory T cells. Relish A distinct member of the Drosophila NFκB transcription factor family that induces the expression of several antimicrobial peptides in response to Gram-negative bacteria. resistance A general immune strategy aimed at reducing or eliminating pathogens; compare with avoidance and tolerance.


Immunology_Janeway

Immunology_Janeway. resistance A general immune strategy aimed at reducing or eliminating pathogens; compare with avoidance and tolerance. respiratory burst An oxygen-requiring metabolic change in neutrophils and macrophages that have taken up opsonized particles, such as complementor antibody-coated bacteria, by phagocytosis. It leads to the production of toxic metabolites that are involved in killing the engulfed microorganisms. restriction factors Host proteins that act in a cell-autonomous manner to inhibit the replication of retroviruses such as HIV. retinoic acid Signaling molecule derived from vitamin A with many roles in the body. It is thought to be involved in the induction of immunological tolerance in the gut. retrotranslocation complex The return of endoplasmic reticulum proteins to the cytosol.


Immunology_Janeway

Immunology_Janeway. retrotranslocation complex The return of endoplasmic reticulum proteins to the cytosol. retrovirus A single-stranded RNA virus that uses the viral enzyme reverse transcriptase to transcribe its genome into a DNA intermediate that integrates into the host-cell genome to undergo viral replication. reverse transcriptase Viral RNA-dependent DNA polymerase that is found in retroviruses and transcribes the viral genomic RNA into DNA during the life cycle of retroviruses (such as HIV). Rheb A small GTPase that activates mTOR when in its GTP-bound form, and is inactivated by a GTPase-activating protein (GAP) complex TSC1/2. rheumatic fever Disease caused by antibodies elicited by infection with some Streptococcus species. These antibodies cross-react with kidney, joint, and heart antigens. rheumatoid arthritis (RA) A common inﬂammatory joint disease that is probably due to an autoimmune response.


Immunology_Janeway

Immunology_Janeway. rheumatoid arthritis (RA) A common inﬂammatory joint disease that is probably due to an autoimmune response. rheumatoid factor An anti-IgG antibody of the IgM class first identified in patients with rheumatoid arthritis, but which is also found in healthy individuals. Rho See Rho family small GTPase proteins. Rho family small GTPase proteins Several distinct small GTPase family members that regulate the actin cytoskeleton in response to signaling through various receptors. Examples: Rac, Rho, and Cdc42. Rictor See mTORC2. RIG-I (retinoic acid-inducible gene I) See RIG-I-like receptors (RLRs). RIG-I-like receptors (RLRs) A small family of intracellular viral sensors that use a carboxy terminal RNA helicase-like domain in detection of various forms of viral RNA. These signal through MAVS to activate antiviral immunity. Examples include RIG-I, MDA-5, and LGP2.


Immunology_Janeway

Immunology_Janeway. RIP2 A CARD domain containing serine-threonine kinase that functions in signaling by NOD proteins to activate the NFκB transcription factor. Riplet An E3 ubiquitin ligase involved in signaling by RIG-I and MDA-5 for the activation of MAVS. rituximab A chimeric antibody to CD20 used to eliminate B cells in treatment of non-Hodgkin's lymphoma. R-loops A structure formed when transcribed RNA displaces the nontemplate strand of the DNA double helix at switch regions in the immunoglobulin constant-region gene cluster. R-loops are thought to promote class switch recombination. RNA exosome A multisubunit complex involved in processing and editing of RNA. ruxolitinib An inhibitor of JAK1 and JAK2 approved for treatment of myelofibrosis.


Immunology_Janeway

Immunology_Janeway. RNA exosome A multisubunit complex involved in processing and editing of RNA. ruxolitinib An inhibitor of JAK1 and JAK2 approved for treatment of myelofibrosis. S1PR1 A G protein-coupled receptor expressed on circulating lymphocytes that binds the chemotactic phospholipid, sphingosine 1-phosphate, which forms a chemotactic gradient that promotes the egress of non-activated lymphocytes out of secondary lymphoid tissues into the efferent lymphatics and blood. See also CD69. SAP (SLAM-associated protein) An intracellular adaptor protein involved in signaling by SLAM (signaling lymphocyte activation molecule). Inactivating mutations in this gene cause X-linked lymphoproliferative (XLP) syndrome. scaffolds Adaptor-type proteins with multiple binding sites, which bring together specific proteins into a functional signaling complex.


Immunology_Janeway

Immunology_Janeway. scaffolds Adaptor-type proteins with multiple binding sites, which bring together specific proteins into a functional signaling complex. scavenger receptors Receptors on macrophages and other cells that bind to numerous ligands, such as bacterial cell-wall components, and remove them from the blood. The Kupffer cells in the liver are particularly rich in scavenger receptors. Includes SR-A I, SR-A II, and MARCO. scid Mutation in mice that causes severe combined immunodeficiency. It was eventually found to be due to mutation of the DNA repair protein DNA-PK. SCID See severe combined immunodeficiency. seasonal allergic rhinoconjunctivitis IgE-mediated allergic rhinitis and conjunctivitis caused by exposure to specific seasonally occurring antigens, for example grass or weed pollens. Commonly called hay fever.


Immunology_Janeway

Immunology_Janeway. Sec61 A multisubunit transmembrane protein pore complex that resides in the membrane of the endoplasmic reticulum and allows peptides to be translocated from the ER lumen into the cytoplasm. second messengers Small molecules or ions (such as Ca2+) that are produced in response to a signal; they act to amplify the signal and carry it to the next stage within the cell. Second messengers generally act by binding to and modifying the activities of enzymes. secondary granules Type of granule in neutrophils that stores certain antimicrobial peptides. secondary immune response The immune response that occurs in response to a second exposure to an antigen. In comparison with the primary response, it starts sooner after exposure, produces greater levels of antibody, and produces class-switched antibodies. It is generated by the reactivation of memory lymphocytes.


Immunology_Janeway

Immunology_Janeway. secondary immunization A second or booster injection of an antigen, given some time after the initial immunization. It stimulates a secondary immune response. secondary immunodeficiencies Deficiencies in immune function that are a consequence of infection (e.g., HIV infection), other diseases (e.g., leukemia), malnutrition, etc.. secondary lymphoid follicle A follicle containing a germinal center of proliferating activated B cells during an ongoing adaptive immune response. secondary lymphoid organs See peripheral lymphoid organs. secondary lymphoid tissues See peripheral lymphoid organs. secretory component (SC) Fragment of the polymeric immunoglobulin receptor that remains after cleavage and is attached to secreted IgA after transport across epithelial cells. secretory IgA (SIgA) Polymeric IgA antibody (mainly dimeric) containing bound J chain and secretory component. It is the predominant form of immunoglobulin in most human secretions.


Immunology_Janeway

Immunology_Janeway. secretory IgA (SIgA) Polymeric IgA antibody (mainly dimeric) containing bound J chain and secretory component. It is the predominant form of immunoglobulin in most human secretions. secretory phospholipase A2 Antimicrobial enzyme present in tears and saliva and also secreted by the Paneth cells of the gut. segmented filamentous bacteria (SFB) Referring to commensal Gram-positive Firmicute species and members of the Clostridiaceae family that adhere to the intestinal wall of rodents and several other species that induce TH17 and IgA responses. selectins Family of cell-adhesion molecules on leukocytes and endothelial cells that bind to sugar moieties on specific glycoproteins with mucin-like features. self antigens The potential antigens on the tissues of an individual, against which an immune response is not usually made except in the case of autoimmunity. self-tolerance The failure to make an immune response against the body’s own antigens.


Immunology_Janeway

Immunology_Janeway. self-tolerance The failure to make an immune response against the body’s own antigens. sensitization The acute adaptive immune response made by susceptible individuals on first exposure to an allergen. In some of these individuals, subsequent exposure to the allergen will provoke an allergic reaction. sensitized In allergy, describes an individual who has made an IgE response on initial encounter with an environmental antigen and who manifests IgE-producing memory B cells. Subsequent allergen exposure can elicit an allergic response. sepsis Bacterial infection of the bloodstream. This is a very serious and frequently fatal condition. septic shock Systemic shock reaction that can follow infection of the bloodstream with endotoxin-producing Gram-negative bacteria. It is caused by the systemic release of TNF-α and other cytokines. Also called endotoxic shock.


Immunology_Janeway

Immunology_Janeway. sequence motif A pattern of nucleotides or amino acids shared by different genes or proteins that often have related functions. serine protease inhibitor (serpin) Class of proteins that inhibit various proteases, originally referring to those specific to serine proteases. seroconversion The phase of an infection when antibodies against the infecting agent are first detectable in the blood. serotypes Name given to a strain of bacteria, or other pathogen, that can be distinguished from other strains of the same species by specific antibodies. serum sickness A usually self-limiting immunological hypersensitivity reaction originally seen in response to the therapeutic injection of large amounts of foreign serum (now most usually evoked by the injection of drugs such as penicillin). It is caused by the formation of immune complexes of the antigen and the antibodies formed against it, which become deposited in the tissues, especially the kidneys.


Immunology_Janeway

Immunology_Janeway. severe combined immunodeficiency (SCID) Type of immune deficiency (due to various causes) in which both B-cell (antibody) and T-cell responses are lacking; it is fatal if not treated. severe congenital neutropenia (SCN) An inherited condition in which the neutrophil count is persistently extremely low. This is in contrast to cyclic neutropenia, in which neutrophil numbers ﬂuctuate from near normal to very low or absent, with an approximate cycle time of 21 days. SH2 (Src homology 2) domain See Src-family protein tyrosine kinases. shear-resistant rolling The capacity of neutrophils to maintain attached to the vascular endothelium under high rates of ﬂow—or shear—enabled by specialized plasma membrane extensions called slings. shingles Disease caused when herpes zoster virus (the virus that causes chickenpox) is reactivated later in life in a person who has had chickenpox.


Immunology_Janeway

Immunology_Janeway. shingles Disease caused when herpes zoster virus (the virus that causes chickenpox) is reactivated later in life in a person who has had chickenpox. SHIP (SH2-containing inositol phosphatase) An SH2-containing inositol phosphatase that removes the phosphate from PIP3 to produce PIP2. shock The potentially fatal circulatory collapse caused by the systemic actions of cytokines such as TNF-α. SHP (SH2-containing phosphatase) An SH2-containing protein phosphatase. signal joint The noncoding joint formed in DNA by the recombination of RSSs during V(D)J recombination. Cf. coding joint. signal peptide The short N-terminal peptide sequence responsible for directing newly synthesized proteins into the secretory pathway. signal transducers and activators of transcription (STATs) See Janus kinase (JAK) family.


Immunology_Janeway

Immunology_Janeway. signal transducers and activators of transcription (STATs) See Janus kinase (JAK) family. signaling scaffold A configuration of proteins and modifications, such as phosphorylation or ubiquitination, that facilitates signaling by binding various enzymes and their substrates. single-chain antibody Referring to the heavy-chain-only IgGs produced by camelids or shark species that lack the light chain present in conventional antibodies. single-nucleotide polymorphisms (SNPs) Positions in the genome that differ by a single base between individuals. single-positive thymocytes A mature T cell that expresses either the CD4 or the CD8 co-receptor, but not both. single-stranded RNA (ssRNA) Normally confined to the nucleus and cytoplasm, this normal molecular form serves as a ligand for TLR-7, TLR-8, and TLR-9 when it is present in endosomes, as during parts of a viral life cycle.