Immunology_Janeway

Immunology_Janeway. C1 complex, C1 Protein complex activated as the first step in the classical pathway of complement activation, composed of C1q bound to two molecules each of the proteases C1r and C1s. Binding of a pathogen or antibody to C1q activates C1r, which cleaves and activates C1s, which cleaves C4 and C2. C1 inhibitor (C1INH) An inhibitor protein for C1 that binds and inactivates C1r:C1s enzymatic activity. Deficiency in C1INH causes hereditary angioedema through production of vasoactive peptides that cause subcutaneous and laryngeal swelling. C2 Complement protein of the classical and lectin pathways that is cleaved by the C1 complex to yield C2b and C2a. C2a is an active protease that forms part of the classical C3 convertase C4bC2a. C3 Complement protein on which all complement activation pathways converge. C3 cleavage forms C3b, which can bind covalently to microbial surfaces, where it promotes destruction by phagocytes.


Immunology_Janeway

Immunology_Janeway. C3 Complement protein on which all complement activation pathways converge. C3 cleavage forms C3b, which can bind covalently to microbial surfaces, where it promotes destruction by phagocytes. C3 convertase Enzyme complex that cleaves C3 to C3b and C3a on the surface of a pathogen. The C3 convertase of the classical and lectin pathways is formed from membrane-bound C4b complexed with the protease C2a. The alternative pathway C3 convertase is formed from membrane-bound C3b complexed with the protease Bb. C3(H2O)Bb See fluid-phase C3 convertase. C3a See anaphylatoxins. C3b See C3. C3b2Bb The C5 convertase of the alternative pathway of complement activation. C3bBb The C3 convertase of the alternative pathway of complement activation. C3dg Breakdown product of iC3b that remains attached to the microbial surface, where it can bind complement receptor CR2. C3f A small fragment of C3b that is removed by factor I and MCP to leave iC3b on the microbial surface.


Immunology_Janeway

Immunology_Janeway. C3f A small fragment of C3b that is removed by factor I and MCP to leave iC3b on the microbial surface. C4 Complement protein of the classical and lectin pathways. C4 is cleaved by C1s to C4b, which forms part of the classical C3 convertase. C4b-binding protein (C4BP) A complement-regulatory protein that inactivates the classical pathway C3 convertase formed on host cells by displacing C2a from the C4bC2a complex. C4BP binds C4b attached to host cells, but cannot bind C4b attached to pathogens. C4b2a C3 convertase of the classical and lectin pathways of complement activation. C4b2a3b C5 convertase of the classical and lectin pathways of complement activation. C5 convertase Enzyme complex that cleaves C5 to C5a and C5b. C5a See anaphylatoxins. C5a receptor The cell-surface receptor for the pro-inﬂammatory C5a fragment of complement, present on macrophages and neutrophils. C5b Fragment of C5 that initiates the formation of the membrane-attack complex (MAC).


Immunology_Janeway

Immunology_Janeway. C5b Fragment of C5 that initiates the formation of the membrane-attack complex (MAC). C5L2 (GPR77) Non-signaling decoy receptor for C5a expressed by phagocytes. C6, C7, C8, C9 Complement proteins that act with C5b to form the membrane-attack complex, producing a pore that leads to lysis of the target cell. calcineurin A cytosolic serine/threonine phosphatase with a crucial role in signaling via the T-cell receptor. The immunosuppressive drugs cyclosporin A and tacrolimus inactivate calcineurin, suppressing T-cell responses. calmodulin Calcium-binding protein that is activated by binding Ca2+; it is then able to bind to and regulate the activity of a wide variety of enzymes. calnexin A chaperone protein in the endoplasmic reticulum (ER) that binds to partly folded members of the immunoglobulin superfamily of proteins and retains them in the ER until folding is complete.


Immunology_Janeway

Immunology_Janeway. calnexin A chaperone protein in the endoplasmic reticulum (ER) that binds to partly folded members of the immunoglobulin superfamily of proteins and retains them in the ER until folding is complete. calprotectin A complex of heterodimers of the antimicrobial peptides S100A8 and S100A9, which sequester zinc and manganese from microbes. Produced in abundance by neutrophils, and in lesser amounts by macrophages and epithelial cells. calreticulin A chaperone protein in the endoplasmic reticulum that, together with ERp57 and tapasin, forms the peptide-loading complex that loads peptides onto newly synthesized MHC class I molecules. cancer immunoediting A process that occurs during the development of a cancer when it is acquiring mutations that favor its survival and escape from immune responses, such that cancer cells with these mutations are selected for survival and growth.


Immunology_Janeway

Immunology_Janeway. cancer-testis antigens Proteins expressed by cancer cells that are normally expressed only in male germ cells in the testis. capping A process occurring in the nucleus in which the modified purine 7-methylguanosine is added to the 5ʹ phosphate of the first nucleotide of the RNA transcript. capsular polysaccharides See capsulated bacteria. capsulated bacteria Referring to bacteria surrounded by a polysaccharide shell that resists actions of phagocytes, resulting in pus formation at the site of infection. Also called pyogenic (pus-forming) bacteria. carboxypeptidase N (CPN) A metalloproteinase that inactivates C3a and C5a. CPN deficiency causes a condition of recurrent angioedema. cardiolipin A lipid found in many bacteria and in the inner mitochondrial membrane that is a ligand recognized by some human γ:δ T cells. caspase 8 An initiator caspase activated by various receptors that activates the process of apoptosis.


Immunology_Janeway

Immunology_Janeway. caspase 8 An initiator caspase activated by various receptors that activates the process of apoptosis. caspase 11 This caspase is homologous to human capsase 4 and 5. Its expression is induced by TLR signaling. Intracellular LPS can directly activate it, leading to pyroptosis. caspase recruitment domain (CARD) A protein domain present in some receptor tails that can dimerize with other CARD-domain-containing proteins, including caspases, thus recruiting them into signaling pathways. caspases A family of cysteine proteases that cleave proteins at aspartic acid residues. They have important roles in apoptosis and in the processing of cytokine pro-polypeptides. cathelicidins Family of antimicrobial peptides that in humans has one member. cathelin A cathepsin L inhibitor. cathepsins A family of proteases using cysteine at their active site that frequently function in processing antigens taken into the vesicular pathway.


Immunology_Janeway

Immunology_Janeway. cathelin A cathepsin L inhibitor. cathepsins A family of proteases using cysteine at their active site that frequently function in processing antigens taken into the vesicular pathway. CC chemokines One of the two main classes of chemokines, distinguished by two adjacent cysteines (C) near the amino terminus. They have names CCL1, CCL2, etc. See Appendix IV for a list of individual chemokines. CCL9 (MIP-1γ) Chemokine made by follicle-associated epithelial cells and binds CCR6, recruiting activated T and B cells, NK cells, and dendritic cells into GALT. CCL19 Chemokine made by dendritic cells and stromal cells in T-cell zones of lymph nodes that binds CCR7 and functions to attract naive T cells. CCL20 Chemokine made by follicle-associated epithelial cells and binds CCR6, recruiting activated T and B cells, NK cells, and dendritic cells into GALT.


Immunology_Janeway

Immunology_Janeway. CCL20 Chemokine made by follicle-associated epithelial cells and binds CCR6, recruiting activated T and B cells, NK cells, and dendritic cells into GALT. CCL21 Chemokine made by dendritic cells and stromal cells in T cell zones of lymph nodes that binds CCR7 and functions to attract naive T cells. CCL25 (TECK) Chemokine made by small-intestinal epithelial cells that binds CCR9 to recruit gut-homing T and B cells. CCL28 (MEC, mucosal epithelial chemokine) Chemokine made by colonic intestinal cells, salivary gland, and lactating mammary gland cells that binds CCR10 to recruit B lymphocytes producing IgA into these tissues. CCR1 Chemokine receptor expressed by neutrophils, monocytes, B cells, and dendritic cells, that binds several chemokines, including CCL6 and CCL9. CCR6 Chemokine receptor expressed by follicular and marginal zone B cells and dendritic cells that binds CCL20.


Immunology_Janeway

Immunology_Janeway. CCR6 Chemokine receptor expressed by follicular and marginal zone B cells and dendritic cells that binds CCL20. CCR7 Chemokine receptor expressed by all naive T and B cells, and some memory T and B cells, such as central memory T cells, that binds CCL19 and CCL21 made by dendritic cells and stromal cells in lymphoid tissues. CCR9 Chemokine receptor expressed by dendritic cells, T cells, and thymocytes, and some γ:δT cells, that binds CCL25 that mediates recruitment of gut-homing cells. CCR10 Chemokine receptor expressed by many cells that binds CCL27 and CCL28 that mediates intestinal recruitment of IgA-producing B lymphocytes. CD1 Small family of MHC class I-like proteins that are not encoded in the MHC and can present glycolipid antigens to CD4 T cells. CD3 complex The invariant proteins CD3γ, δ, and ε, and the dimeric ζ chains, which form the signaling complex of the T-cell receptor. Each of them contains one or more ITAM signaling motifs in their cytoplasmic tails.


Immunology_Janeway

Immunology_Janeway. CD4 The co-receptor for T-cell receptors that recognize peptide antigens bound to MHC class II molecules. It binds to the lateral face of the MHC molecule. CD8 The co-receptor for T-cell receptors that recognize peptide antigens bound to MHC class I molecules. It binds to the lateral face of the MHC molecule. CD11b (αM integrin) Integrin expressed by macrophages and some dendritic cells that functions with β2 integrin (CD18) as complement receptor 3 (CR3). CD19 See B-cell co-receptor. CD21 Another name for complement receptor 2 (CR2). See also B-cell co-receptor. CD22 An inhibitory receptor on B cells that binds sialic acid-modified glycoproteins commonly found on mammalian cells and contains an ITIM motif in its cytoplasmic tail. CD23 The low-affinity Fc receptor for IgE.


Immunology_Janeway

Immunology_Janeway. CD23 The low-affinity Fc receptor for IgE. CD25 Also known as IL-2 receptorα (IL-2Rα), this is the high-affinity component of the IL-2 receptor, which also includes IL-2Rβ and the common γ chain. It is upregulated by activated T cells and is constitutively expressed by Treg cells to confer responsiveness to IL-2. CD27 A TNF receptor-family protein constitutively expressed on naive T cells that binds CD70 on dendritic cells and delivers a potent co-stimulatory signal to T cells early in the activation process. CD28 An activating receptor on T cells that binds to the B7 co-stimulatory molecules present on specialized antigen-presenting cells such as dendritic cells. CD28 is the major co-stimulatory receptor on naive T cells. CD30, CD30 ligand CD30 on B cells and CD30 ligand (CD30L) on helper T cells are co-stimulatory molecules involved in stimulating the proliferation of antigen-activated naive B cells.


Immunology_Janeway

Immunology_Janeway. CD30, CD30 ligand CD30 on B cells and CD30 ligand (CD30L) on helper T cells are co-stimulatory molecules involved in stimulating the proliferation of antigen-activated naive B cells. CD31 A cell-adhesion molecule found both on lymphocytes and at endothelial cell junctions. CD31–CD31 interactions are thought to enable leukocytes to leave blood vessels and enter tissues. CD40, CD40 ligand CD40 on B cells and CD40 ligand (CD40L, CD154) on activated helper T cells are co-stimulatory molecules whose interaction is required for the proliferation and class switching of antigen activated naive B cells. CD40 is also expressed by dendritic cells, and here the CD40–CD40L interaction provides co-stimulatory signals to naive T cells.


Immunology_Janeway

Immunology_Janeway. CD40 ligand deficiency An immunodeficiency disease in which little or no IgG, IgE, or IgA antibody is produced and even IgM responses are deficient, but serum IgM levels are normal to high. It is due to a defect in the gene encoding CD40 ligand (CD154), which prevents class switching from occurring. Also known as X-linked hyper IgM syndrome, reﬂecting location of gene that encodes CD40L on the X chromosome and phenotype of elevated IgM antibody relative to other immunoglobulins. CD44 Also known as phagocytic glycoprotein-1 (Pgp1), CD44 is a cell-surface glycoprotein expressed by naive lymphocytes and upregulated on activated T cells. It is a receptor for hyaluronic acid and functions in cell–cell and cell–extracellular matrix adhesion. High expression of CD44 is used as a marker for effector and memory T cells.


Immunology_Janeway

Immunology_Janeway. CD45 A transmembrane tyrosine phosphatase found on all leukocytes. It is expressed in different isoforms on different cell types, including the different subtypes of T cells. Also called leukocyte common antigen, it is a generic marker for hematopoietically derived cells, with the exception of erythrocytes. CD45RO An alternatively spliced variant of CD45 that serves as a marker for memory T cells. CD48 See 2B4. CD59, protectin Cell-surface protein that protects host cells from complement damage by blocking binding of C9 to the C5b678 complex, thus preventing MAC formation. CD69 A cell-surface protein that is rapidly expressed by antigen-activated T cells. It acts to down-modulate the expression of the sphingosine 1 phosphate receptor 1 (S1PR1), thereby retaining activated T cells within T-cell zones of secondary lymphoid tissues as they divide and differentiate into effector T cells.


Immunology_Janeway

Immunology_Janeway. CD70 The ligand for CD27 that is expressed on activated dendritic cells and delivers a potent co-stimulatory signal to T cells early in the activation process. CD81 See B-cell co-receptor. CD84 See SLAM (signaling lymphocyte activation molecule). CD86 (B7-2) A transmembrane protein of the immunoglobulin superfamily that is expressed on antigen-presenting cells and binds to CD28 expressed by T cells. CD94 A C-type lectin that is a subunit of the KLR-type receptors of NK cells. CD103 Integrin αE:β7, a cell-surface marker on a subset of dendritic cells in the gastrointestinal tract that are involved in inducing tolerance to antigens from food and the commensal microbiota. CD127 Also known as IL-7 receptor α (IL-7Rα), which pairs with the common γ chain of the IL-2 receptor family to form the IL-7 receptor. It is expressed by naive T cells and a subset of memory T cells to support their survival.


Immunology_Janeway

Immunology_Janeway. celiac disease A chronic condition of the upper small intestine caused by an immune response directed at gluten, a complex of proteins present in wheat, oats, and barley. The gut wall becomes chronically inﬂamed, the villi are destroyed, and the gut’s ability to absorb nutrients is compromised. cell-adhesion molecules Cell-surface proteins of several different types that mediate the binding of one cell to other cells or to extracellular matrix proteins. Integrins, selectins, and members of the immunoglobulin gene superfamily (such as ICAM-1) are among the cell-adhesion molecules important in the operation of the immune system. cell-mediated immune responses An adaptive immune response in which antigen-specific effector T cells have the main role. The immunity to infection conferred by such a response is called cell-mediated immunity. A primary cell-mediated immune response is the T-cell response that occurs the first time a particular antigen is encountered.


Immunology_Janeway

Immunology_Janeway. cellular hypersensitivity reactions A hypersensitivity reaction mediated largely by antigen-specific T lymphocytes. cellular immunology The study of the cellular basis of immunity. central lymphoid organs, central lymphoid tissues The sites of lymphocyte development; in humans, these are the bone marrow and thymus. B lymphocytes develop in bone marrow, whereas T lymphocytes develop within the thymus from bone marrow-derived progenitors. Also called the primary lymphoid organs. central memory T cells (TCM) Memory lymphocytes that express CCR7 and recirculate between blood and secondary lymphoid tissues similarly to naive T cells. They require restimulation in secondary lymphoid tissues to become fully mature effector T cells. central tolerance Immunological tolerance to self antigens that is established while lymphocytes are developing in central lymphoid organs. Cf. peripheral tolerance.


Immunology_Janeway

Immunology_Janeway. central tolerance Immunological tolerance to self antigens that is established while lymphocytes are developing in central lymphoid organs. Cf. peripheral tolerance. centroblasts Large, rapidly dividing activated B cells present in the dark zone of germinal centers in follicles of peripheral lymphoid organs. centrocytes Small B cells that derive from centroblasts in the germinal centers of follicles in peripheral lymphoid organs; they populate the light zone of the germinal center. cGAS (cyclic GAMP synthase) A cytosolic enzyme that is activated by double-stranded DNA to form cyclic guanosine monophosphate-adenosine monophoshate. See cyclic dinucleotides (CDNs). checkpoint blockade Approach to tumor therapy that attempts to interfere with the normal inhibitory signals that regulate lymphocytes.


Immunology_Janeway

Immunology_Janeway. checkpoint blockade Approach to tumor therapy that attempts to interfere with the normal inhibitory signals that regulate lymphocytes. Chediak–Higashi syndrome A defect in phagocytic cell function caused by a defect in a protein involved in intracellular vesicle fusion. Lysosomes fail to fuse properly with phagosomes, and killing of ingested bacteria is impaired. chemokines Small chemoattractant protein that stimulates the migration and activation of cells, especially phagocytic cells and lymphocytes. Chemokines have a central role in inﬂammatory responses. Properties of individual chemokines are listed in Appendix IV. chemotaxis Cellular movement occurring in response to chemical signals in the environment. chimeric antigen receptor (CAR) Engineered fusion proteins composed of extracellular antigen-specific receptors (e.g., single-chain antibody) and intracellular signaling domains that activate and co-stimulate, expressed in T cells for use in cancer immunotherapy.


Immunology_Janeway

Immunology_Janeway. chronic allograft vasculopathy Chronic damage that can lead to late failure of transplanted organs. Arteriosclerosis of graft blood vessels leads to hypoperfusion of the graft and its eventual fibrosis and atrophy. chronic granulomatous disease (CGD) An immunodeficiency in which multiple granulomas form as a result of defective elimination of bacteria by phagocytic cells. It is caused by defects in the NADPH oxidase system of enzymes that generate the superoxide radical involved in bacterial killing. An autoinﬂammatory disease due to defects in the gene NLRP3, one of the components of the inﬂammasome. chronic rejection Late failure of a transplanted organ, which can be due to immunological or nonimmunological causes. CIIV An early endocytic compartment containing MHC class II molecules in dendritic cells.


Immunology_Janeway

Immunology_Janeway. CIIV An early endocytic compartment containing MHC class II molecules in dendritic cells. class I cytokine receptors A group of receptors for the hematopoietin superfamily of cytokines. These include receptors using the common γ chain for IL-2, IL-4, IL-7, IL-15, and IL-21, and a common β chain for GM-CSF, IL-3, and IL-5. class II-associated invariant chain peptide (CLIP) A peptide of variable length cleaved from the invariant chain (Ii) by proteases. It remains associated with the MHC class II molecule in an unstable form until it is removed by the HLA-DM protein. class II cytokine receptors A group of heterodimeric receptors for a family of cytokines that includes interferon (IFN)-α, IFN-β, IFN-γ, and IL-10.


Immunology_Janeway

Immunology_Janeway. class II cytokine receptors A group of heterodimeric receptors for a family of cytokines that includes interferon (IFN)-α, IFN-β, IFN-γ, and IL-10. class switching, class switch recombination A somatic gene recombination process in activated B cells that replaces one heavy-chain constant region with one of a different isotype, switching the isotype of antibodies from IgM to the production of IgG, IgA, or IgE. This affects the antibody effector functions but not their antigen specificity. Also known as isotype switching. Cf. somatic hypermutation. classes The class of an antibody is defined by the type of heavy chain it contains. There are five main antibody classes: IgA, IgD, IgM, IgG, and IgE, containing heavy chains α, δ, μ, γ, and ε, respectively. The IgG class has several subclasses. See also isotypes. classical C3 convertase The complex of activated complement components C4b2a, which cleaves C3 to C3b on pathogen surfaces in the classical pathway of complement activation.


Immunology_Janeway

Immunology_Janeway. classical C3 convertase The complex of activated complement components C4b2a, which cleaves C3 to C3b on pathogen surfaces in the classical pathway of complement activation. classical MHC class I genes MHC class I genes whose proteins function by presenting peptide antigens for recognition by T cells. Cf. nonclassical MHC class Ib. classical monocyte The major form of monocyte in circulation capable of recruitment to sites of inﬂammation and differentiation into macrophages. classical pathway The complement-activation pathway that is initiated by C1 binding either directly to bacterial surfaces or to antibody bound to the bacteria, thus ﬂagging the bacteria as foreign. See also alternative pathway, lectin pathway. classically activated macrophage See M1 macrophages. cleavage stimulation factor A multi-subunit protein complex involved in the modification of the 3ʹ end of pre-messenger RNA for the addition of the polyadenine (polyA) tail.


Immunology_Janeway

Immunology_Janeway. cleavage stimulation factor A multi-subunit protein complex involved in the modification of the 3ʹ end of pre-messenger RNA for the addition of the polyadenine (polyA) tail. clonal deletion The elimination of immature lymphocytes when they bind to self antigens, which produces tolerance to self as required by the clonal selection theory of adaptive immunity. Clonal deletion is the main mechanism of central tolerance and can also occur in peripheral tolerance. clonal expansion The proliferation of antigen-specific lymphocytes in response to antigenic stimulation that precedes their differentiation into effector cells. It is an essential step in adaptive immunity, allowing rare antigen-specific cells to increase in number so that they can effectively combat the pathogen that elicited the response.


Immunology_Janeway

Immunology_Janeway. clonal selection theory The central paradigm of adaptive immunity. It states that adaptive immune responses derive from individual antigen-specific lymphocytes that are self-tolerant. These specific lymphocytes proliferate in response to antigen and differentiate into antigen-specific effector cells that eliminate the eliciting pathogen, and into memory cells to sustain immunity. The theory was formulated by Macfarlane Burnet and in earlier forms by Niels Jerne and David Talmage. clone A population of cells all derived from the same progenitor cell. clonotypic Describes a feature unique to members of a clone. For example, the distribution of antigen receptors in the lymphocyte population is said to be clonotypic, as the cells of a given clone all have identical antigen receptors. Clostridium difficile Gram-positive anaerobic toxogenic spore-forming bacterium frequently associated with severe colitis following treatment with certain broad-spectrum antibiotics.


Immunology_Janeway

Immunology_Janeway. Clostridium difficile Gram-positive anaerobic toxogenic spore-forming bacterium frequently associated with severe colitis following treatment with certain broad-spectrum antibiotics. c-Maf A transcription factor acting in the development of TFH cells. coagulation system A collection of proteases and other proteins in the blood that trigger blood clotting when blood vessels are damaged. coding joint DNA join formed by the imprecise joining of a V gene segment to a (D)J gene segment during recombination of the immunoglobulin or T-cell receptor genes. It is the joint retained in the rearranged gene. Cf. signal joint. codominant Describes the situation in which the two alleles of a gene are expressed in roughly equal amounts in the heterozygote. Most genes show this property, including the highly polymorphic MHC genes. collectins A family of calcium-dependent sugar-binding proteins (lectins) containing collagen-like sequences. An example is mannose-binding lectin (MBL).


Immunology_Janeway

Immunology_Janeway. collectins A family of calcium-dependent sugar-binding proteins (lectins) containing collagen-like sequences. An example is mannose-binding lectin (MBL). combinatorial diversity The diversity among antigen receptors generated by combining separate units of genetic information, comprising two types. First, receptor gene segments are joined in many different combinations to generate diverse receptor chains; second, two different receptor chains (heavy and light in immunoglobulins; α and β, or γ and δ, in T-cell receptors) are combined to make the antigen-recognition site. commensal microbiota, commensal microorganisms Microorganisms (predominantly bacteria) that normally live harmlessly in symbiosis with their host (for example the gut bacteria in humans and other animals). Many commensals confer a positive benefit on their host in some way. common β chain A transmembrane polypeptide (CD131) that is a common subunit for receptor of the cytokines IL-3, IL-5, and GM-CSF.


Immunology_Janeway

Immunology_Janeway. common β chain A transmembrane polypeptide (CD131) that is a common subunit for receptor of the cytokines IL-3, IL-5, and GM-CSF. common γ chain (γc) A transmembrane polypeptide chain (CD132) that is common to a subgroup of cytokine receptors. common lymphoid progenitor (CLP) Stem cell that can give rise to all the types of lymphocytes with the exception of innate lymphoid cells (ILCs). common mucosal immune system The mucosal immune system as a whole, the name reﬂecting the fact that lymphocytes that have been primed in one part of the mucosal system can recirculate as effector cells to other parts of the mucosal system. common myeloid progenitor (CMP) Stem cells that can give rise to the myeloid cells of the immune system—macrophages, granulocytes, mast cells, and dendritic cells of the innate immune system. This stem cell also gives rise to megakaryocytes and red blood cells.


Immunology_Janeway

Immunology_Janeway. common variable immunodeficiencies (CVIDs) A relatively common deficiency in antibody production in which only one or a few isotypes are affected. It can be due to a variety of genetic defects. complement A set of plasma proteins that act together as a defense against pathogens in extracellular spaces. The pathogen becomes coated with complement proteins that facilitate its removal by phagocytes and that can also kill certain pathogens directly. Activation of the complement system can be initiated in several different ways. See classical pathway, alternative pathway, lectin pathway. complement activation The activation of the normally inactive proteins of the complement system that occurs on infection. See classical pathway, alternative pathway, lectin pathway. complement proteins See C1, C2, C3, etc..


Immunology_Janeway

Immunology_Janeway. complement proteins See C1, C2, C3, etc.. complement receptors (CRs) Cell-surface proteins of various types that recognize and bind complement proteins that have become bound to an antigen such as a pathogen. Complement receptors on phagocytes enable them to identify and bind pathogens coated with complement proteins, and to ingest and destroy them. See CR1, CR2, CR3, CR4, CRIg, and the C1 complex. complement regulatory proteins Proteins that control complement activity and prevent complement from being activated on the surfaces of host cells. complement system A set of plasma proteins that act together as a defense against pathogens in extracellular spaces. The pathogen becomes coated with complement proteins that facilitate its removal by phagocytes and that can also kill certain pathogens directly. Activation of the complement system can be initiated in several different ways. See classical pathway, alternative pathway, lectin pathway.


Immunology_Janeway

Immunology_Janeway. complementarity-determining regions (CDRs) Parts of the V domains of immunoglobulins and T-cell receptors that determine their antigen specificity and make contact with the specific ligand. The CDRs are the most variable part of antigen receptor, and contribute to the diversity of these proteins. There are three such regions (CDR1, CDR2, and CDR3) in each V domain. conformational epitopes, discontinuous epitopes Antigenic structure (epitope) on a protein antigen that is formed from several separate regions in the sequence of the protein brought together by protein folding. Antibodies that bind conformational epitopes bind only native folded proteins. conjugate vaccines Antibacterial vaccines made from bacterial capsular polysaccharides bound to proteins of known immunogenicity, such as tetanus toxoid. constant Ig domains (C domains) Type of protein domain that makes up the constant regions of each chain of an immunoglobulin molecule.


Immunology_Janeway

Immunology_Janeway. constant Ig domains (C domains) Type of protein domain that makes up the constant regions of each chain of an immunoglobulin molecule. constant region, C region That part of an immunoglobulin or a T-cell receptor that is relatively constant in amino acid sequence between different molecules. Also known as the Fc region in antibodies. The constant region of an antibody determines its particular effector function. Cf. variable region. continuous epitope, linear epitope Antigenic structure (epitope) in a protein that is formed by a single small region of amino acid sequence. Antibodies that bind continuous epitopes can bind to the denatured protein. The epitopes detected by T cells are continuous. Also called a linear epitope. conventional (or classical) dendritic cells (cDCs) The lineage of dendritic cells that mainly participates in antigen presentation to, and activation of, naive T cells. Cf. plasmacytoid dendritic cells.


Immunology_Janeway

Immunology_Janeway. co-receptors Cell-surface protein that increases the sensitivity of a receptor to its ligand by binding to associated ligands and participating in signaling. The antigen receptors on T cells and B cells act in conjunction with co-receptors, which are either CD4 or CD8 on T cells, and a co-receptor complex of three proteins, one of which is the complement receptor CR2, on B cells. cortex The outer part of a tissue or organ; in lymph nodes it refers to the follicles, which are mainly populated by B cells. corticosteroids Family of drugs related to natural steroids such as cortisone. Corticosteroids can kill lymphocytes, especially developing thymocytes, inducing apoptotic cell death. They are medically useful anti-inﬂammatory and immunosuppressive agents. co-stimulatory molecules Cell-surface proteins on antigen-presenting cells that deliver co-stimulatory signals to naive T cells. Examples are the B7 molecules on dendritic cells, which are ligands for CD28 on naive T cells.


Immunology_Janeway

Immunology_Janeway. co-stimulatory receptors Cell-surface receptors on naive lymphocytes through which the cells receive signals additional to those received through the antigen receptor, and which are necessary for the full activation of the lymphocyte. Examples are CD30 and CD40 on B cells, and CD27 and CD28 on T cells. CR1 (CD35) A receptor expressed by phagocytic cells that binds to C3b. It stimulates phagocytosis and inhibits C3 convertase formation on host-cell surfaces. CR2 (CD21) Complement receptor that is part of the B-cell co-receptor complex. It binds to antigens coated with breakdown products of C3b, especially C3dg, and, by cross-linking the B-cell receptor, enhances sensitivity to antigen at least 100-fold. It is also the receptor used by the Epstein–Barr virus to infect B cells.


Immunology_Janeway

Immunology_Janeway. CR3 (CD11b:CD18) Complement receptor 3. A β2 integrin that acts both as an adhesion molecule and as a complement receptor. CR3 on phagocytes binds iC3b, a breakdown product of C3b on pathogen surfaces, and stimulates phagocytosis. CR4 (CD11c:CD18) A β2 integrin that acts both as an adhesion molecule and as a complement receptor. CR4 on phagocytes binds iC3b, a breakdown product of C3b on pathogen surfaces, and stimulates phagocytosis. CRAC channel Channels in the lymphocyte plasma membrane that open to let calcium ﬂow into the cell during the response of the cell to antigen. Channel opening is induced by release of calcium from the endoplasmic reticulum. C-reactive protein An acute-phase protein that binds to phosphocholine, a constituent of the surface C-polysaccharide of the bacterium Streptococcus pneumoniae and of many other bacteria, thus opsonizing them for uptake by phagocytes. CRIg (complement receptor of the immunoglobulin family)


Immunology_Janeway

Immunology_Janeway. CRIg (complement receptor of the immunoglobulin family) A complement receptor that binds to inactivated forms of C3b. Crohn’s disease Chronic inﬂammatory bowel disease thought to result from an abnormal overresponsiveness to the commensal gut microbiota. cross-matching A test used in blood typing and histocompatibility typing to determine whether donor and recipient have antibodies against each other’s cells that might interfere with successful transfusion or grafting. cross-presentation The process by which extracellular proteins taken up by dendritic cells can give rise to peptides presented by MHC class I molecules. It enables antigens from extracellular sources to be presented by MHC class I molecules and activate CD8 T cells.


Immunology_Janeway

Immunology_Janeway. cross-priming Activation of CD8 T cells by dendritic cells in which the antigenic peptide presented by MHC class I molecules is derived from an exogenous protein (i.e., by cross-presentation), rather than produced within the dendritic cells directly. Cf. direct presentation. cryptdins α-Defensins (antimicrobial peptides) made by the Paneth cells of the small intestine. cryptic epitopes Any epitope that cannot be recognized by a lymphocyte receptor until the antigen has been broken down and processed. cryptopatches Aggregates of lymphoid tissue in the gut wall that are thought to give rise to isolated lymphoid follicles. CstF-64 Subunit of cleavage stimulation factor that favors polyadenylation at pAS leading to the secreted form of IgM. C-terminal Src kinase (Csk) A kinase that phosphorylates the C-terminal tyrosine of Src-family kinases in lymphocytes, thus inactivating them.


Immunology_Janeway

Immunology_Janeway. C-terminal Src kinase (Csk) A kinase that phosphorylates the C-terminal tyrosine of Src-family kinases in lymphocytes, thus inactivating them. CTLA-4 A high-affinity inhibitory receptor on T cells for B7 molecules; its binding inhibits T-cell activation. C-type lectins Large class of carbohydrate-binding proteins that require Ca2+ for binding, including many that function in innate immunity. cutaneous lymphocyte antigen (CLA) A cell-surface molecule that is involved in lymphocyte homing to the skin in humans. CVIDs See common variable immunodeficiencies. CX3CR1 Chemokine receptor expressed by monocytes, macrophages, NK cells, and activated T cells that binds CXCL1 (Fractalkine). CXC chemokines One of the two main classes of chemokines, distinguished by a Cys-X-Cys (CXC) motif near the amino terminus. They have names CXCL1, CXCL2, etc. See Appendix IV for a list of individual chemokines.


Immunology_Janeway

Immunology_Janeway. CXCL12 (SDF-1) Chemokine produced by stromal cells in the dark zone of the germinal center that binds CXCR4 expressed by centroblasts. CXCL13 Chemokine produced in the follicle and the light zone of the germinal center that binds CXCR5 expressed on circulating B cells and centrocytes. CXCR5 A chemokine receptor expressed by circulating B cells and activated T cells that binds the chemokine CXCL13 and directs cell migration into the follicle. cyclic dinucleotides (CDNs) Cyclic dimers of guanylate and/or adenylate monophosphate that are produced by various bacteria as second messengers and detected by STING. cyclic guanosine monophosphate-adenosine monophosphate (cyclic GMP-AMP or cGAMP) See cyclic dinucleotides (CDNs).


Immunology_Janeway

Immunology_Janeway. cyclic guanosine monophosphate-adenosine monophosphate (cyclic GMP-AMP or cGAMP) See cyclic dinucleotides (CDNs). cyclic neutropenia A dominantly inherited disease in which neutrophil numbers ﬂuctuate from near normal to very low or absent, with an approximate cycle time of 21 days. This is in contrast to severe congenital neutropenia (SCN), in which the inherited defect results in persistently low neutrophil numbers. cyclic reentry model An explanation of the behavior of B cells in lymphoid follicles, proposing that activated B cells in germinal centers lose and gain expression of the chemokine receptor CXCR4 and thus move from the light zone to the dark zone and back again under the inﬂuence of the chemokine CXCL12. cyclophilins A family of prolylisomerases that affect protein folding, that also bind cyclosporin A to produce a complex that associates with calcineurin, preventing its activation by calmodulin.


Immunology_Janeway

Immunology_Janeway. cyclophilins A family of prolylisomerases that affect protein folding, that also bind cyclosporin A to produce a complex that associates with calcineurin, preventing its activation by calmodulin. cyclophosphamide A DNA alkylating agent that is used as an immunosuppressive drug. It acts by killing rapidly dividing cells, including lymphocytes proliferating in response to antigen. cyclosporin A (CsA) A powerful noncytotoxic immunosuppressive drug that inhibits signaling from the T-cell receptor, preventing T-cell activation and effector function. It binds to cyclophilin, and the complex formed binds to and inactivates the phosphatase calcineurin. cystic fibrosis Disease caused by defect in CFTR gene, leading to abnormally thick mucus and causing serious recurrent infections of the lung. cytidine deaminase activity (CDA) An enzymatic activity exhibited by AID-APOBEC family proteins of agnathan species that may mediate rearrangement and assembly of complete VLR genes.


Immunology_Janeway

Immunology_Janeway. cytidine deaminase activity (CDA) An enzymatic activity exhibited by AID-APOBEC family proteins of agnathan species that may mediate rearrangement and assembly of complete VLR genes. cytokines Proteins made by a cell that affect the behavior of other cells, particularly immune cells. Cytokines made by lymphocytes are often called interleukins (abbreviated IL). Cytokines and their receptors are listed in Appendix III. Cf. chemokines. cytomegalovirus UL16 protein A nonessential glycoprotein of cytomegalovirus that is recognized by innate receptors expressed by NK cells. cytosol One of several major compartments within cells containing elements such as the cytoskeleton, and mitochondria, and separated by membranes from distinct compartments such as the nucleus and vesicular system. cytotoxic T cells T cells that can kill other cells, typically CD8 T cells defending against intracellular pathogens that live or reproduce in the cytosol, but in some cases also CD4 T cells.


Immunology_Janeway

Immunology_Janeway. cytotoxic T cells T cells that can kill other cells, typically CD8 T cells defending against intracellular pathogens that live or reproduce in the cytosol, but in some cases also CD4 T cells. daclizumab Antibody to human CD25 used to block IL-2 receptor signaling in T cells for treatment of rejection in renal transplantation. DAG See diacylglycerol. damage-associated molecular patterns (DAMPs) See pathogen-associated molecular patterns (PAMPs). DAP10, DAP12 Signaling chains containing ITAMS that are associated with the tails of some activating receptors on NK cells. dark zone See germinal center. DC-SIGN A lectin on the dendritic-cell surface that binds ICAM-3 with high affinity. DDX41 (DEAD box polypeptide 41) A candidate DNA sensor of the RLR family that appears to signal through the STING pathway.


Immunology_Janeway

Immunology_Janeway. DDX41 (DEAD box polypeptide 41) A candidate DNA sensor of the RLR family that appears to signal through the STING pathway. death effector domain (DED) Protein-interaction domain originally discovered in proteins involved in programmed cell death or apoptosis. As part of the intracellular domains of some adaptor proteins, death domains are involved in transmitting pro-inﬂammatory and/or pro-apoptotic signals. death-inducing signaling complex (DISC) A multi-protein complex that is formed by signaling through members of the ‘death receptor’ family of apoptosis-inducing cellular receptors, such as Fas. It activates the caspase cascade to induce apoptosis. decay-accelerating factor (DAF or CD55) A cell-surface protein that protects cells from lysis by complement. Its absence causes the disease paroxysmal nocturnal hemoglobinuria. Dectin-1 A phagocytic receptor on neutrophils and macrophages that recognizes β-1,3-linked glucans, which are common components of fungal cell walls.


Immunology_Janeway

Immunology_Janeway. Dectin-1 A phagocytic receptor on neutrophils and macrophages that recognizes β-1,3-linked glucans, which are common components of fungal cell walls. defective ribosomal products (DRiPs) Peptides translated from introns in improperly spliced mRNAs, translations of frameshifts, or improperly folded proteins, which are recognized and tagged by ubiquitin for degradation by the proteasome. defensins See α-defensins, β-defensins. delayed-type hypersensitivity reactions A form of cell-mediated immunity elicited by antigen in the skin stimulating sensitized Th1 CD4 lymphocytes and CD8 lymphocytes. It is called delayed-type hypersensitivity because the reaction appears hours to days after antigen is injected. Referred to as type IV hypersensitivity in the historic Gell and Coombs classification.


Immunology_Janeway

Immunology_Janeway. dendritic cells Bone marrow-derived cells found in most tissues, including lymphoid tissues. There are two main functional subsets. Conventional dendritic cells take up antigen in peripheral tissues, are activated by contact with pathogens, and travel to the peripheral lymphoid organs, where they are the most potent stimulators of T-cell responses. Plasmacytoid dendritic cells can also take up and present antigen, but their main function in an infection is to produce large amounts of the antiviral interferons as a result of pathogen recognition through receptors such as TLRs. Both these types of dendritic cells are distinct from the follicular dendritic cell that presents antigen to B cells in lymphoid follicles. dendritic epidermal T cells (dETCs) A specialized class of γ:δ T cells found in the skin of mice and some other species, but not humans. They express Vγ5:Vδ1 and may interact with ligands such as Skint-1 expressed by keratinocytes.


Immunology_Janeway

Immunology_Janeway. dephosphorylation The removal of a phosphate group from a molecule, usually a protein. depleting antibodies Immunosuppressive monoclonal antibodies that trigger the destruction of lymphocytes in vivo. They are used for treating episodes of acute graft rejection. diacyl and triacyl lipoproteins Ligands for the Toll-like receptors TLR1:TLR2 and TLR2:TLR6. diacylglycerol A lipid intracellular signaling molecule formed from membrane inositol phospholipids that are cleaved by the action of phospholipase C-γ after the activation of many different receptors. The diacylglycerol stays in the membrane and activates protein kinase C and RasGRP, which further propagate the signal. diapedesis The movement of blood cells, particularly leukocytes, from the blood across blood vessel walls into tissues. differentiation antigens Referring to a category of genes with restricted expression patterns that can be targeted as antigens by immunotherapies in treatment of cancers.


Immunology_Janeway

Immunology_Janeway. differentiation antigens Referring to a category of genes with restricted expression patterns that can be targeted as antigens by immunotherapies in treatment of cancers. DiGeorge syndrome Recessive genetic immunodeficiency disease in which there is a failure to develop thymic epithelium. Parathyroid glands are also absent and there are anomalies in the large blood vessels. direct allorecognition Host recognition of a grafted tissue that involves donor antigen-presenting cells leaving the graft, migrating via the lymph to regional lymph nodes, and activating host T cells bearing the corresponding T-cell receptors. direct presentation The process by which proteins produced within a given cell give rise to peptides presented by MHC class I molecules. This may refer to antigen-presenting cells, such as dendritic cells, or to nonimmune cells that will become the targets of CTLs.


Immunology_Janeway

Immunology_Janeway. dislocation In reference to viral defense mechanisms, the degradation of newly synthesized MHC class I molecules by viral proteins. disseminated intravascular coagulation (DIC) Blood clotting occurring simultaneously in small vessels throughout the body in response to disseminated TNF-α, which leads to the massive consumption of clotting proteins, so that the patient’s blood cannot clot appropriately. Seen in septic shock. diversion colitis Inﬂammation and necrosis of intestinal enterocytes following surgical diversion of normal ﬂow of fecal contents due to impaired metabolism resulting from loss of short-chain fatty acids derived from microbiota. diversity gene segment (DH) Short DNA sequences that form a join between the V and J gene segments in rearranged immunoglobulin heavy-chain genes and in T-cell receptor βand δ-chain genes. See gene segments.


Immunology_Janeway

Immunology_Janeway. DN1, DN2, DN3, DN4 Substages in the development of CD4+CD8+ double-positive T cells in the thymus. Rearrangement of the TCRβ-chain locus starts at DN2 and is completed by DN4. DNA-dependent protein kinase (DNA-PK) Protein kinase in the DNA repair pathway involved in the rearrangement of immunoglobulin and T-cell receptor genes. DNA ligase IV Enzyme responsible for joining the DNA ends to produce the coding joint during V(D)J recombination. DNA transposons Genetic elements encoding their own transposase that can insert themselves into and excise themselves from the DNA genomes of a host. DNA vaccination Vaccination by introduction into skin and muscle of DNA encoding the desired antigen; the expressed protein can then elicit antibody and T-cell responses. donor lymphocyte infusion (DLI) Transfer of mature lymphocytes (i.e., T cells) from donor into patients during bone marrow transplantation for cancer treatment to help eliminate residual tumor.


Immunology_Janeway

Immunology_Janeway. donor lymphocyte infusion (DLI) Transfer of mature lymphocytes (i.e., T cells) from donor into patients during bone marrow transplantation for cancer treatment to help eliminate residual tumor. double-negative thymocytes Immature T cells in the thymus that lack expression of the two co-receptors CD4 and CD8 and represent the progenitors to the remaining T cells developing in the thymus. In a normal thymus, these represent about 5% of thymocytes. double-positive thymocytes Immature T cells in the thymus that are characterized by expression of both the CD4 and the CD8 co-receptor proteins. They represent the majority (about 80%) of thymocytes and are the progenitors to the mature CD4 and CD8 T cells. double-strand break repair (DSBR) A nonhomologous end joining pathway of DNA repair used in the completion of isotype switching. double-stranded RNA (dsRNA) A chemical structure that is a replicative intermediate of many viruses that is recognized by TLR-3.


Immunology_Janeway

Immunology_Janeway. double-stranded RNA (dsRNA) A chemical structure that is a replicative intermediate of many viruses that is recognized by TLR-3. Down syndrome cell adhesion molecule (Dscam) See Dscam. DR4, DR5 Members of the TNFR superfamily expressed by many cell types that can be activated by the TRAIL to induce apoptosis. draining lymph nodes A lymph node downstream of a site of infection that receives antigens and microbes from the site via the lymphatic system. Draining lymph nodes often enlarge enormously during an immune response and can be palpated; they were originally called swollen glands. Dscam A member of the immunoglobulin superfamily that in insects is thought to opsonize invading bacteria and aid their engulfment by phagocytes. It can be made in a multiplicity of different forms as a result of alternative splicing.


Immunology_Janeway

Immunology_Janeway. dysbiosis Altered balance of microbial species comprising the microbiota resulting from a variety of causes (e.g., antibiotics, genetic disorders) and frequently associated with outgrowth of pathogenic organisms such as Clostridium difficile. dysregulated self Refers to changes that take place in infected or malignant cells that alter expression of various surface receptors that can be detected by the innate immune system. E3 ligase An enzymatic activity that directs the transfer of a ubiquitin molecule from an E2 ubiquitin-conjugating enzyme onto a specific protein target. early-onset sarcoidosis Disease associated with activating NOD2 mutations characterized by inﬂammation in tissues such as liver. early pro-B cell See pro-B cells. EBI2 (GPR183) A chemokine receptor that binds oxysterols and regulates B-cell movement to the outer follicular and interfollicular regions during early phases of B-cell activation in lymphoid tissues.


Immunology_Janeway

Immunology_Janeway. E-cadherin Integrin expressed by epithelial cells important in forming the adherens junctions between adjacent cells. edema Swelling caused by the entry of ﬂuid and cells from the blood into the tissues; it is one of the cardinal features of inﬂammation. effector caspases Intracellular proteases that are activated as a result of an apoptotic signal and mediate the cellular changes associated with apoptosis. To be distinguished from initiator caspases, which act upstream of effector caspases to initiate the caspase cascade. effector CD4 T cells The subset of differentiated effector T cells carrying the CD4 co-receptor molecule, which includes the TH1, TH2, TH17, and regulatory T cells.


Immunology_Janeway

Immunology_Janeway. effector CD4 T cells The subset of differentiated effector T cells carrying the CD4 co-receptor molecule, which includes the TH1, TH2, TH17, and regulatory T cells. effector lymphocytes The cells that differentiate from naive lymphocytes after initial activation by antigen and can then mediate the removal of pathogens from the body without further differentiation. They are distinct from memory lymphocytes, which must undergo further differentiation to become effector lymphocytes. effector mechanisms Those processes by which pathogens are destroyed and cleared from the body. Innate and adaptive immune responses use most of the same effector mechanisms to eliminate pathogens. effector memory T cells (TEM) Memory lymphocytes that recirculate between blood and peripheral tissues and are specialized for rapid maturation into effector T cells after restimulation with antigen in non-lymphoid tissues.


Immunology_Janeway

Immunology_Janeway. effector modules This term refers to a set of immune mechanisms, either cell-mediated and humoral, innate or adaptive, that act together in the elimination of a particular category of pathogen. effector T lymphocytes The T cells that perform the functions of an immune response, such as cell killing and cell activation, that clear the infectious agent from the body. There are several different subsets, each with a specific role in an immune response. electrostatic interactions Chemical interaction occurring between charged atoms, as in the charged amino acid side chains and an ion in a salt bridge. elimination phase Stage of anti-tumor immune response that detects and eliminates cancer cells, also called immune surveillance. elite controllers A subset of HIV-infected long-term non-progressors who have clinically undetectable levels of virus without antiretroviral therapy.


Immunology_Janeway

Immunology_Janeway. elite controllers A subset of HIV-infected long-term non-progressors who have clinically undetectable levels of virus without antiretroviral therapy. ELL2 A transcription elongation factor that favors the polyadenylation at pAS leading to the secreted form of IgM. endocrine Describes the action of a biologically active molecule such as a hormone or cytokine that is secreted by one tissue into the blood and acts on a distant tissue. Cf. autocrine, paracrine. endogenous pyrogens Cytokines that can induce a rise in body temperature. endoplasmic reticulum aminopeptidase associated with antigen processing (ERAAP) Enzyme in the endoplasmic reticulum that trims polypeptides to a size at which they can bind to MHC class I molecules. A system of enzymes in the endoplasmic reticulum that recognizes incompletely or misfolded proteins and assures their eventual degradation.


Immunology_Janeway

Immunology_Janeway. A system of enzymes in the endoplasmic reticulum that recognizes incompletely or misfolded proteins and assures their eventual degradation. endosteum The region in bone marrow adjacent to the inner surface of the bone; hematopoietic stem cells are initially located there. endothelial activation The changes that occur in the endothelial walls of small blood vessels as a result of inﬂammation, such as increased permeability and the increased production of cell-adhesion molecules and cytokines. endothelial cell Cell type that forms the endothelium, the epithelium of a blood vessel wall. endothelial protein C receptor (EPCR) A nonclassical MHC class I protein induced on endothelial cells that can interact with the blood coagulation factor XIV (protein C) and can be recognized by some γ:δ T cells. endothelium The epithelium that forms the walls of blood capillaries and the lining of larger blood vessels.


Immunology_Janeway

Immunology_Janeway. endothelium The epithelium that forms the walls of blood capillaries and the lining of larger blood vessels. endotoxins Toxins derived from bacterial cell walls released by damaged cells. They can potently induce cytokine synthesis and in large amounts can cause a systemic reaction called septic shock or endotoxic shock. enteroadherent Escherichia coli Referring to multiple strains of E. coli capable of attachment to, and infection and destruction of cells of the intestinal microvilli, causing colitis and diarrheagenic diseases. eomesodermin A transcription factor involved in development and function of certain types of NK cells, ILCs, and CD8 T cells. eosinophilia An abnormally large number of eosinophils in the blood. eosinophils A type of white blood cell containing granules that stain with eosin. It is thought to be important chieﬂy in defense against parasitic infections, but is also medically important as an effector cell in allergic reactions.


Immunology_Janeway

Immunology_Janeway. eotaxins CC chemokines that act predominantly on eosinophils, including CCL11 (eotaxin 1), CCL24 (eotaxin 2), and CCL26 (eotaxin 3). epitope A site on an antigen recognized by an antibody or an antigen receptor. T-cell epitopes are short peptide bound to MHC molecules. B-cell epitopes are typically structural motifs on the surface of the antigen. Also called an antigenic determinant. epitope spreading Increase in diversity of responses to autoantigens as the response persists, as a result of responses being made to epitopes other than the original one. equilibrium phase Stage of anti-tumor immune response when immunoediting allows the immune response to continuously shape the antigenic character of cancer cells. Erk Extracellular signal-related kinase, a protein kinase that is the MAPK for one module of the T-cell receptor signaling pathway. Erk also functions in other receptors in other cell types.


Immunology_Janeway

Immunology_Janeway. Erk Extracellular signal-related kinase, a protein kinase that is the MAPK for one module of the T-cell receptor signaling pathway. Erk also functions in other receptors in other cell types. ERp57 A chaperone protein involved in loading peptide onto MHC class I molecules in the endoplasmic reticulum. error-prone ‘translesion’ DNA polymerases A DNA polymerase operates during DNA repair, such as Polη which can repair a basic lesion by incorporating untemplated nucleotides into the newly formed DNA strand. escape mutants Mutants of pathogens that are changed in such a way that they can evade the immune response against the original pathogen. escape phase Final stage of anti-tumor immune response when immunoediting has removed the expression of antigenic targets such that the cancer cells are no loner detected by the immune system. E-selectin See selectins.


Immunology_Janeway

Immunology_Janeway. E-selectin See selectins. etanercept Fc fusion protein containing the p75 subunit of the TNF receptor that neutralizes TNF-α used for treatment of rheumatoid arthritis and other inﬂammatory diseases. eukaryotic initiation factor 2 (eIF2α) Subunit of eukaryotic initiation factor that helps form the preinitiation complex that begins protein translation from mRNA. When it is phosphorylated by PKR, protein translation is suppressed. eukaryotic initiation factor 3 (eIF3) Multisubunit complex that acts in formation of the 43S preinitiation complex. It can bind interferon-induced transmembrane (IFIT) proteins which thereby suppress translation of viral proteins. exogenous pyrogen Any substance originating outside the body that can induce fever, such as the bacterial lipopolysaccharide LPS. Cf. endogenous pyrogens. exotoxins A protein toxin produced and secreted by a bacterium.


Immunology_Janeway

Immunology_Janeway. exotoxins A protein toxin produced and secreted by a bacterium. experimental autoimmune encephalomyelitis (EAE) An inﬂammatory disease of the central nervous system that develops after mice are immunized with neural antigens in a strong adjuvant. extrachromosomal DNA DNA not contained within chromosomes, such as the circular DNA produced by V(D)J recombination occurring between RSSs in the same chromosomal orientation and is eventually lost from the cell. extravasation The movement of cells or ﬂuid from within blood vessels into the surrounding tissues. extrinsic pathway of apoptosis A pathway triggered by extracellular ligands binding to specific cell-surface receptors (death receptors) that signal the cell to undergo programmed cell death (apoptosis).


Immunology_Janeway

Immunology_Janeway. Fab fragment Antibody fragment composed of a single antigen-binding arm of an antibody without the Fc region, produced by cleavage of IgG by the enzyme papain. It contains the complete light chain plus the amino-terminal variable region and first constant region of the heavy chain, held together by an interchain disulfide bond. F(abʹ)2 fragment Antibody fragment composed of two linked antigen-binding arms (Fab fragments) without the Fc regions, produced by cleavage of IgG with the enzyme pepsin. factor B Protein in the alternative pathway of complement activation, in which it is cleaved to Ba and an active protease, Bb, the latter binding to C3b to form the alternative pathway C3 convertase, C3bBb. factor D A serine protease in the alternative pathway of complement activation, which cleaves factor B into Ba and Bb. factor H Complement-regulatory protein in plasma that binds C3b and competes with factor B to displace Bb from the convertase.


Immunology_Janeway

Immunology_Janeway. factor H Complement-regulatory protein in plasma that binds C3b and competes with factor B to displace Bb from the convertase. factor H binding protein (fHbp) A protein produced by the pathogen Neisseria meningitidis that recruits factor H to its membrane, thereby inactivating C3b deposited on its surface, and evading destruction by complement. factor I Complement-regulatory protease in plasma that cleaves C3b to the inactive derivative iC3b, thus preventing the formation of a C3 convertase. factor I deficiency A genetically determined lack of the complement-regulatory protein factor I. This results in uncontrolled complement activation, so that complement proteins rapidly become depleted. Those with the deficiency suffer repeated bacterial infections, especially with ubiquitous pyogenic bacteria. factor P Plasma protein released by activated neutrophils that stabilizes the C3 convertase C3bBb of the alternative pathway.


Immunology_Janeway

Immunology_Janeway. factor P Plasma protein released by activated neutrophils that stabilizes the C3 convertase C3bBb of the alternative pathway. familial cold autoinflammatory syndrome (FCAS) An episodic autoinﬂammatory disease caused by mutations in the gene NLRP3, encoding NLRP3, a member of the NOD-like receptor family and a component of the inﬂammasome. The symptoms are induced by exposure to cold. familial hemophagocytic lymphohistiocytosis (FHL) A family of progressive and potentially lethal inﬂammatory diseases caused by an inherited deficiency of one of several proteins involved in the formation or release of cytolytic granules. Large numbers of polyclonal CD8-positive T cells accumulate in lymphoid and other organs, and this is associated with activated macrophages that phagocytose blood cells, including erythrocytes and leukocytes.


Immunology_Janeway

Immunology_Janeway. familial Mediterranean fever (FMF) A severe autoinﬂammatory disease, inherited as an autosomal recessive disorder. It is caused by mutation in the gene (MEFV) that encodes the protein pyrin, which is expressed in granulocytes and monocytes. In patients with this disorder, defective pyrin is thought to spontaneously activate inﬂammasomes. farmer’s lung A hypersensitivity disease caused by the interaction of IgG antibodies with large amounts of an inhaled antigen in the alveolar wall of the lung, causing alveolar wall inﬂammation and compromising respiratory gas exchange. Fc fragment, Fc region The carboxy-terminal halves of the two heavy chains of an IgG molecule disulfide-bonded to each other by the residual hinge region. It is produced by cleavage of IgG by papain. In the complete antibody this portion is often called the Fc region.


Immunology_Janeway

Immunology_Janeway. Fc receptors Family of cell-surface receptors that bind the Fc portions of different immunoglobulins: Fcγ receptors bind IgG, for example, and Fcε receptors bind IgE. FCAS See familial cold autoinflammatory syndrome. FcεRI The high affinity receptor for the Fc region of IgE. Expressed primarily on the surface of mast cells and basophils. When multivalent antigen interacts with IgE that is bound to FcεRI and cross-links nearby receptors, it causes activation of the receptor-bearing cell. FcγR1 (CD64) Fc receptor highly expressed by monocytes and macrophages that has the highest affinity of the Fc receptors for IgG. FcγRIIB-1 An inhibitory receptor on B cells that recognizes the Fc portion of IgG antibodies. FcγRIIB-1 contains an ITIM motif in its cytoplasmic tail.


Immunology_Janeway

Immunology_Janeway. FcγRIIB-1 An inhibitory receptor on B cells that recognizes the Fc portion of IgG antibodies. FcγRIIB-1 contains an ITIM motif in its cytoplasmic tail. FcγRIII Cell-surface receptors that bind the Fc portion of IgG molecules. Most Fcγ receptors bind only aggregated IgG, allowing them to discriminate bound antibody from free IgG. Expressed variously on phagocytes, B lymphocytes, NK cells, and follicular dendritic cells, the Fcγ receptors have a key role in humoral immunity, linking antibody binding to effector cell functions. FcRn (neonatal Fc receptor) Neonatal Fc receptor, a receptor that transports IgG from mother to fetus across the placenta, and across other epithelia such as the epithelium of the gut. FHL See familial hemophagocytic lymphohistiocytosis. fibrinogen-related proteins (FREPs) Members of the immunoglobulin superfamily that are thought to have a role in innate immunity in the freshwater snail Biomphalaria glabrata.


Immunology_Janeway

Immunology_Janeway. fibrinogen-related proteins (FREPs) Members of the immunoglobulin superfamily that are thought to have a role in innate immunity in the freshwater snail Biomphalaria glabrata. ficolins Carbohydrate-binding proteins that can initiate the lectin pathway of complement activation. They are members of the collectin family and bind to the N-acetylglucosamine present on the surface of some pathogens. fingolimod Small-molecule immunosuppressive drug that interferes with the actions of sphingosine, leading to retention of effector T cells in lymphoid organs. FK506 See tacrolimus. FK-binding proteins (FKBPs) Group of prolyl isomerases related to the cyclophilins and bind the immunosuppressive drug FK506 (tacrolimus). flagellin A protein that is the major constituent of the ﬂagellum, the tail-like structure used in bacterial locomotion. TLR-5 recognizes intact ﬂagellin protein that has dissociated from the ﬂagellum.


Immunology_Janeway

Immunology_Janeway. fluid-phase C3 convertase Short-lived alternative pathway C3 convertase, C3(H20)Bb, that is continually produced at a low level in the plasma that can initiate activation of the alternative pathway of complement. fMet-Leu-Phe (fMLF) receptor A pattern recognition receptor for the peptide fMet-Leu-Phe, which is specific to bacteria, on neutrophils and macrophages. fMet-Leu-Phe acts as a chemoattractant. folic acid A B vitamin, derivatives of folic acid produced by various bacteria can be bound by the nonclassical MHC class Ib protein MR1 for recognition by MAIT cells. follicle-associated epithelium Specialized epithelium separating the lymphoid tissues of the gut wall from the intestinal lumen. As well as enterocytes it contains microfold cells, through which antigens enter the lymphoid organs from the gut. follicles An area of predominantly B cells in a peripheral lymphoid organ, such as a lymph node, which also contains follicular dendritic cells.


Immunology_Janeway

Immunology_Janeway. follicles An area of predominantly B cells in a peripheral lymphoid organ, such as a lymph node, which also contains follicular dendritic cells. follicular B cells The majority population of long-lived recirculating conventional B cells found in the blood, the spleen, and the lymph nodes. Also known as B-2 B cells. follicular dendritic cell (FDC) A cell type of uncertain origin in B-cell follicles of peripheral lymphoid organs that captures antigen:antibody complexes using non-internalized Fc receptors and presents them to B cells for internalization and processing during the germinal center reaction. follicular helper T cell (TFH) Type of effector CD4 T cell that resides in lymphoid follicles and provides help to B cells for antibody production. framework regions Relatively invariant regions that provide a protein scaffold for the hypervariable regions in the V domains of immunoglobulins and T-cell receptors.


Immunology_Janeway

Immunology_Janeway. framework regions Relatively invariant regions that provide a protein scaffold for the hypervariable regions in the V domains of immunoglobulins and T-cell receptors. Freund’s complete adjuvant Emulsion of oil and water containing killed mycobacteria used to enhance immune responses to experimental antigens. fungi A kingdom of single-celled and multicellular eukaryotic organisms, including the yeasts and molds, that can cause a variety of diseases. Immunity to fungi is complex and involves both humoral and cell-mediated responses. Fyn See Src-family tyrosine kinases. γ:δ T cells Subset of T lymphocytes bearing a T-cell receptor composed of the antigen-recognition chains, γ and δ, assembled in a γ:δ heterodimer. γ:δ T-cell receptors Antigen receptor carried by a subset of T lymphocytes that is distinct from the α:βT-cell receptor. It is composed of a γ and a δ chain, which are produced from genes that undergo gene rearrangement.


Immunology_Janeway

Immunology_Janeway. γ-glutamyl diaminopimelic acid (iE-DAP) A product of degradation of the peptidoglycan of Gram-negative bacteria. It is sensed by NOD1. GAP See GTPase-activating proteins. GEFs See guanine nucleotide exchange factors. gene rearrangement The process of somatic recombination of gene segments in the immunoglobulin and T-cell receptor genetic loci to produce a functional gene. This process generates the diversity found in immunoglobulin and T-cell receptor variable regions.


Immunology_Janeway

Immunology_Janeway. gene segments Sets of short DNA sequences at the immunoglobulin and T-cell receptor loci that encode different regions of the variable domains of antigen receptors. Gene segments of each type are joined together by somatic recombination to form a complete variable-domain exon. There are three types of gene segments: V gene segments encode the first 95 amino acids, D gene segments (in heavy-chain and TCRα chain loci only) encode about 5 amino acids, and J gene segments encode the last 10–15 amino acids of the variable domain. There are multiple copies of each type of gene segment in the germline DNA, but only one of each type is joined together to form the variable domain. genetic locus The site of a gene on a chromosome. In the case of the genes for the immunoglobulin and T-cell receptor chains, the term locus refers to the complete collection of gene segments and C-region genes for the given chain.


Immunology_Janeway

Immunology_Janeway. genome-wide association studies (GWASs) Genetic association studies in the general population that look for a correlation between disease frequency and variant alleles by scanning the genomes of many people for the presence of informative single-nucleotide polymorphisms (SNPs). germ-free mice Mice that are raised in the complete absence of intestinal and other microorganisms. Such mice have very depleted immune systems, but they can respond virtually normally to any specific antigen, provided it is mixed with a strong adjuvant. germinal center Sites of intense B-cell proliferation and differentiation that develop in lymphoid follicles during an adaptive immune response. Somatic hypermutation and class switching occur in germinal centers. germline theory An excluded hypothesis that antibody diversity was encoded by a separate germline gene for each antibody, known not to be true for most vertebrates, although cartilaginous fishes do have some rearranged V regions in the germline.


Immunology_Janeway

Immunology_Janeway. glycosylphosphatidylinositol (GPI) tail A glycolipid modification of proteins that can allow attachment to host membranes without the requirement of a transmembrane protein domain. gnathostomes The class of jawed vertebrates comprising most fish and all mammals. These possess an adaptive immunity based on the RAG-mediated V(D)J recombination. gnotobiotic mice See germ-free mice. goblet cells Specialized epithelial cells located in many sites throughout the body responsible for mucus production; important in protection of the epithelium. Goodpasture’s syndrome An autoimmune disease in which autoantibodies against type IV collagen (found in basement membranes) are produced, causing extensive inﬂammation in kidneys and lungs. gout Disease caused by monosodium urate crystals deposited in the cartilaginous tissues of joints, causing inﬂammation. Urate crystals activate the NLRP3 inﬂammasome, which induces inﬂammatory cytokines.


Immunology_Janeway

Immunology_Janeway. G proteins Intracellular GTPases that act as molecular switches in signaling pathways. They bind GTP to induce their active conformation, which is lost when GTO is hydrolyzed to GDP. There are two kinds of G proteins: the heterotrimeric (α, β, γ subunits) receptor-associated G proteins, and the small G proteins, such as Ras and Raf, which act downstream of many transmembrane signaling events. G-protein-coupled receptors (GPCRs) A large class of seven-span transmembrane cell-surface receptors that associate with intracellular heterotrimeric G proteins after ligand binding, and signal by activation of the G protein. Important examples are the chemokine receptors. G-quadruplex A structure formed from G-rich regions of DNA in which four guanine bases form a planar hydrogen-bonded network, or guanine tetrad, that can further stack on other guanine tetrads. G-quadruplexes processed from intronic switch region RNA may target AID back to the switch regions during isotype switching.


Immunology_Janeway

Immunology_Janeway. graft rejection See allograft rejection. graft-versus-host disease (GVHD) An attack on the tissues of the recipient by mature T cells in a bone marrow graft from a nonidentical donor, which can cause a variety of symptoms; sometimes these are severe. graft-versus-leukemia effect A beneficial side-effect of bone marrow grafts given to treat leukemia, in which mature T cells in the graft recognize minor histocompatibility antigens or tumor-specific antigens on the recipient’s leukemic cells and attack them. Gram-negative bacteria Bacteria that fail to retain crystal violet stain following alcohol wash due to a thin peptidoglycan layer. Gram-negative binding proteins (GNBPs) Proteins that act as the pathogen-recognition proteins in the Toll pathway of immune defense in Drosophila.


Immunology_Janeway

Immunology_Janeway. Gram-negative binding proteins (GNBPs) Proteins that act as the pathogen-recognition proteins in the Toll pathway of immune defense in Drosophila. granulocyte-macrophage stimulating factor (GM-CSF) A cytokine involved in the growth and differentiation of cells of the myeloid lineage, including dendritic cells, monocytes and tissue macrophages, and granulocytes. granulocytes White blood cells with multilobed nuclei and cytoplasmic granules. They comprise the neutrophils, eosinophils, and basophils. Also known as polymorphonuclear leukocytes. granuloma A site of chronic inﬂammation usually triggered by persistent infectious agents such as mycobacteria or by a nondegradable foreign body. Granulomas have a central area of macrophages, often fused into multinucleate giant cells, surrounded by T lymphocytes.


Immunology_Janeway

Immunology_Janeway. Grass A serine protease of Drosophila that functions downstream of peptidoglycan-recognition proteins (PGRPs) and Gram-negative binding proteins (GNBPs) to initiate the proteolytic cascade leading to Toll activation. Graves’ disease An autoimmune disease in which antibodies against the thyroid-stimulating hormone receptor cause overproduction of thyroid hormone and thus hyperthyroidism. Griscelli syndrome An inherited immunodeficiency disease that affects the pathway for secretion of lysosomes. It is caused by mutations in a small GTPase Rab27a, which controls the movement of vesicles within cells. group 1 ILCs (ILC1s) The subtype of innate lymphoid cells (ILCs) characterized by IFN-γ production. GTPase-activating proteins (GAP) Regulatory proteins that accelerate the intrinsic GTPase activity of G proteins and thus facilitate the conversion of G proteins from the active (GTP-bound) state to the inactive (GDP-bound) state.


Immunology_Janeway

Immunology_Janeway. guanine nucleotide exchange factors (GEFs) Proteins that can remove the bound GDP from G proteins, thus allowing GTP to bind and activate the G protein. gut-associated lymphoid tissues (GALT) Lymphoid tissues associated with the gastrointestinal tract, comprising Peyer’s patches, the appendix, and isolated lymphoid follicles found in the intestinal wall, where adaptive immune responses are initiated, and by lymphatics to mesenteric lymph nodes. GVHD See graft-versus-host disease. H-2 locus, H-2 genes The major histocompatibility complex of the mouse. Haplotypes are designated by a lower-case superscript, as in H-2b. H-2DM See HLA-DM. H-2O See HLA-DO. H2-M3 A nonclassical MHC class Ib protein in mice that can bind and present peptides having an N-formylated amino terminus for recognition by CD8 T cells. H5N1 avian flu A highly pathogenic inﬂuenza subtype responsible for ‘bird ﬂu’.


Immunology_Janeway

Immunology_Janeway. H5N1 avian flu A highly pathogenic inﬂuenza subtype responsible for ‘bird ﬂu’. haploinsufficient Describes the situation in which the presence of only one normal allele of a gene is not sufficient for normal function. hapten carrier effect Antibody production against a small chemical group, the hapten, following its attachment to a carrier protein for which an immune response has been generated. haptens Any small molecule that can be recognized by a specific antibody but cannot by itself elicit an immune response. A hapten must be chemically linked to a protein molecule to elicit antibody and T-cell responses. Hashimoto’s thyroiditis An autoimmune disease characterized by persistent high levels of antibody against thyroid-specific antigens. These antibodies recruit NK cells to the thyroid, leading to damage and inﬂammation.


Immunology_Janeway

Immunology_Janeway. heavy chain, H chain One of the two types of protein chain in an immunoglobulin molecule, the other being called the light chain. There are several different classes, or isotypes, of heavy chain (α,δ, ε, γ, and μ), each of which confers a distinctive functional activity on the antibody molecule. Each immunoglobulin molecule contains two identical heavy chains. heavy-chain-only IgGs (hcIgGs) Antibodies produced by some camelid species composed of heavy-chain dimers without an associated light chain that retain antigen binding capacity. heavy-chain variable region (VH) Referring to the V region of the heavy chain of an immunoglobulin. helicard See MDA-5. helper CD4 T cells, helper T cells Effector CD4 T cells that stimulate or ‘help’ B cells to make antibody in response to antigenic challenge. TH2, TH1, and the TFH subsets of effector CD4 T cells can perform this function.


Immunology_Janeway

Immunology_Janeway. hemagglutinin (HA) Substances that can cause hemagglutination, such as human antibodies that recognize the ABO blood group antigens on red blood cells, or the inﬂuenza virus hemagglutinin, a glycoprotein that functions in viral fusion with endosome membranes. hematopoietic stem cells (HSCs) Type of pluripotent cell in the bone marrow that can give rise to all the different blood cell types. hematopoietin superfamily Large family of structurally related cytokines that includes growth factors and many interleukins with roles in both adaptive and innate immunity. hemochromatosis protein A protein expressed by intestinal epithelial cells that regulates iron uptake and transport by interacting with the transferrin receptor to decrease its affinity for iron-loaded transferrin.


Immunology_Janeway

Immunology_Janeway. hemolytic disease of the newborn A severe form of Rh hemolytic disease in which maternal anti-Rh antibody enters the fetus and produces a hemolytic anemia so severe that the fetus has mainly immature erythroblasts in the peripheral blood. hemophagocytic lymphohistiocytic (HLH) syndrome A dysregulated expansion of CD8-positive lymphocytes that is associated with macrophage activation. The activated macrophages phagocytose blood cells, including erythrocytes and leukocytes. hepatobiliary route Route whereby mucosally produced dimeric IgA enters the portal veins in the lamina propria, is transported to the liver, and reaches the bile duct by transcytosis. This pathway is not of great significance in humans. heptamer The conserved seven-nucleotide DNA sequence in the recombination signal sequences (RSSs) ﬂanking gene segments in the immunoglobulin and T-cell receptor loci.


Immunology_Janeway

Immunology_Janeway. heptamer The conserved seven-nucleotide DNA sequence in the recombination signal sequences (RSSs) ﬂanking gene segments in the immunoglobulin and T-cell receptor loci. HER-2/neu A receptor tyrosine kinase overexpressed in many cancers, particularly breast cancer, that is the target of trastuzumab (Herceptin) used in its treatment. herd immunity Protection conferred to unvaccinated individuals in a population produced by vaccination of others and reduction in the natural reservoir for infection. hereditary angioedema (HAE) A genetic deficiency of the C1 inhibitor of the complement system. In the absence of C1 inhibitor, spontaneous activation of the complement system can cause diffuse ﬂuid leakage from blood vessels, the most serious consequence of which is swelling of the larynx, leading to suffocation. hereditary hemochromatosis A disease caused by defects in the HFE gene characterized by abnormally high retention of iron in the liver and other organs.


Immunology_Janeway

Immunology_Janeway. hereditary hemochromatosis A disease caused by defects in the HFE gene characterized by abnormally high retention of iron in the liver and other organs. herpes virus entry molecule (HVEM) See B and T lymphocyte attenuator. heterosubtypic immunity Immune protection against a pathogen conferred by infection with a distinct strain, typically with reference to different inﬂuenza A serotypes. heterotrimeric G proteins See G proteins. heterozygous Describes individuals that have two different alleles of a given gene, one inherited from the mother and one from the father. HFE See hemochromatosis protein. high endothelial cells, high endothelial venules (HEV) Specialized small venous blood vessels in lymphoid tissues. Lymphocytes migrate from the blood into lymphoid tissues by attaching to the high endothelial cells in the walls of the venules and squeezing between them.


Immunology_Janeway

Immunology_Janeway. highly active antiretroviral therapy (HAART) A combination of drugs that is used to control HIV infection. It comprises nucleoside analogs that prevent reverse transcription, and drugs that inhibit the viral protease. hinge region The ﬂexible domain that joins the Fab arms to the Fc piece in an immunoglobulin. The ﬂexibility of the hinge region in IgG and IgA molecules allows the Fab arms to adopt a wide range of angles, permitting binding to epitopes spaced variable distances apart. HIP/PAP An antimicrobial C-type lectin secreted by intestinal cells in humans. Also known as RegIIIα. histamine A vasoactive amine stored in mast-cell granules. Histamine released by antigen binding to IgE antibodies bound to mast cells causes the dilation of local blood vessels and the contraction of smooth muscle, producing some of the symptoms of IgE-mediated allergic reactions. Antihistamines are drugs that counter histamine action.


Immunology_Janeway

Immunology_Janeway. histatins Antimicrobial peptides constitutively produced by the parotid, sublingual, and submandibular glands in the oral cavity. Active against pathogenic fungi such as Cryptococcus neoformans and Candida albicans. HIV See human immunodeficiency virus. HLA The genetic designation for the human MHC. Individual loci are designated by upper-case letters, as in HLA-A, and alleles are designated by numbers, as in HLA-A*0201. HLA-DM An invariant MHC protein resembling MHC class II in humans that is involved in loading peptides onto MHC class II molecules. A homologous protein in mice is called H-2M, or sometimes H2-DM. HLA-DO An invariant MHC class II molecule that binds HLA-DM, inhibiting the release of CLIP from MHC class II molecules in intracellular vesicles. A homologous protein in mice is called H-2O or H2-DO. homeostatic chemokines Chemokines that are produced at steady-state to direct the localization of immune cells to lymphoid tissues.


Immunology_Janeway

Immunology_Janeway. homeostatic chemokines Chemokines that are produced at steady-state to direct the localization of immune cells to lymphoid tissues. homing The direction of a lymphocyte into a particular tissue. homing receptors Receptors on lymphocytes for chemokines, cytokines, and adhesion molecules specific to particular tissues, and which enable the lymphocyte to enter that tissue. homozygous Describes individuals that have two identical alleles of a given gene, inherited separately from each parent. host-versus-graft disease (HVGD) Another name for the allograft rejection reaction. The term is used mainly in relation to bone marrow transplantation when immune cells of the host recognize and destroy transplanted bone marrow or hematopoietic stem cells (HSCs).


Immunology_Janeway

Immunology_Janeway. human immunodeficiency virus (HIV) The causative agent of the acquired immune deficiency syndrome (AIDS). HIV is a retrovirus of the lentivirus family that selectively infects macrophages and CD4 T cells, leading to their slow depletion, which eventually results in immunodeficiency. There are two major strains of the virus, HIV-1 and HIV-2, of which HIV-1 causes most disease worldwide. HIV-2 is endemic to West Africa but is spreading. human leukocyte antigen (HLA) See HLA. humanization The genetic engineering of mouse hypervariable loops of a desired specificity into otherwise human antibodies for use as therapeutic agents. Such antibodies are less likely to cause an immune response in people treated with them than are wholly mouse antibodies. humoral Referring to effector proteins in the blood or body ﬂuids, such as antibodies in adaptive immunity, or complement proteins in innate immunity.


Immunology_Janeway

Immunology_Janeway. humoral Referring to effector proteins in the blood or body ﬂuids, such as antibodies in adaptive immunity, or complement proteins in innate immunity. humoral immunity, humoral immune response Immunity due to proteins circulating in the blood, such as antibodies (in adaptive immunity) or complement (in innate immunity). Adaptive humoral immunity can be transferred to unimmunized recipients by the transfer of serum containing specific antibody. HVGD See host-versus-graft disease. hydrophobic interaction Chemical interaction occurring between nearby hydrophobic moieties typically excluding water molecules. 21-hydroxylase An enzyme of non-immune function but encoded in the MHC locus required for normal cortisol synthesis by the adrenal gland. 3-hydroxy-3-methylglutaryl-co-enzyme A (HMG-CoA) reductase Rate-limiting enzyme in the production of cholesterol and a target of cholesterol-lowering drugs such as the statins.


Immunology_Janeway

Immunology_Janeway. 3-hydroxy-3-methylglutaryl-co-enzyme A (HMG-CoA) reductase Rate-limiting enzyme in the production of cholesterol and a target of cholesterol-lowering drugs such as the statins. hygiene hypothesis A hypothesis first proposed in 1989 that reduced exposure to ubiquitous environmental microorganisms was a cause of the increased frequency of patients with allergies observed over the course of the midto late-20th century. hyper IgE syndrome (HIES) Also called Job’s syndrome. A disease characterized by recurrent skin and pulmonary infections and high serum concentrations of IgE. hyper IgM syndrome A group of genetic diseases in which there is overproduction of IgM antibody, among other symptoms. They are due to defects in various genes for proteins involved in class switching such as CD40 ligand and the enzyme AID. See activation-induced cytidine deaminase, CD40 ligand deficiency. hyper IgM type 2 immunodeficiency See activation-induced cytidine deaminase.


Immunology_Janeway

Immunology_Janeway. hyper IgM type 2 immunodeficiency See activation-induced cytidine deaminase. hyperacute graft rejection Immediate rejection reaction caused by preformed natural antibodies that react against antigens on the transplanted organ. The antibodies bind to endothelium and trigger the blood-clotting cascade, leading to an engorged, ischemic graft and rapid death of the organ. hypereosinophilic syndrome Disease associated with an overproduction of eosinophils. hypervariable regions See complementarity-determining regions. hypomorphic mutations Applied to mutations that result in reduced gene function. IκB A cytoplasmic protein that constitutively associates with the NFκB homodimer, composed of p50 and p65 subunits. When IκB is phosphorylated by activated IKK (IκB kinase), IκB becomes degraded and allows the NFκB dimer to be released as an active transcription factor. IκB kinase (IKK) See IKK. iC3b Inactive complement fragment produced by cleavage of C3b.


Immunology_Janeway

Immunology_Janeway. IκB kinase (IKK) See IKK. iC3b Inactive complement fragment produced by cleavage of C3b. ICAMs ICAM-1, ICAM-2, ICAM-3. Cell-adhesion molecules of the immunoglobulin superfamily that bind to the leukocyte integrin CD11a:CD18 (LFA-1). They are crucial in the binding of lymphocytes and other leukocytes to antigen-presenting cells and endothelial cells. ICOS (inducible co-stimulatory) A CD28-related co-stimulatory receptor that is induced on activated T cells and can enhance T-cell responses. It binds a co-stimulatory ligand known as ICOSL (ICOS ligand), which is distinct from the B7 molecules. ICOSL See ICOS. IFI16 (IFN-γ-inducible protein 16) A member of the PYHIN subfamily of NLR (NOD-like receptor) family containing an N-terminal HIN domain. It activates the STING pathway in response to double-stranded DNA.


Immunology_Janeway

Immunology_Janeway. IFIT (IFN-induced protein with tetratricoid repeats) A small family of host proteins induced by interferons that regulate protein translation during infection in part by interactions with eIF3. IFITM (interferon-induced transmembrane protein) A small family of host transmembrane proteins induced by interferons that function in the cell's vesicular compartment to restrain various steps in viral replication. IFN-α, IFN-β Antiviral cytokines produced by a wide variety of cells in response to infection by a virus, and which also help healthy cells resist viral infection. They act through the same receptor, which signals through a Janus-family tyrosine kinase. Also known as the type I interferons. IFN-γ A cytokine of the interferon structural family produced by effector CD4 TH1 cells, CD8 T cells, and NK cells. Its primary function is the activation of macrophages, and it acts through a different receptor from that of the type I interferons.


Immunology_Janeway

Immunology_Janeway. IFN-γ-induced lysosomal thiol reductase (GILT) An enzyme present in the endosomal compartment of many antigen-presenting cells that denatures disulfide bonds to facilitate the degradation and processing of proteins. IFN-λ Also called type III interferons, this family includes IL-28A, IL-28B, and IL-29, which bind a common receptor expressed by a limited set of epithelial tissues. IFN-λ receptor Receptor composed of a unique IL-28Rα subunit and the β subunit of the IL-10 receptor that recognizes IL-28A, IL-28B, and IL-29. Igα, Igβ See B-cell receptor. IgA Immunoglobulin class composed of α heavy chains that can occur in a monomeric and a polymeric (mainly dimeric) form. Polymeric IgA is the main antibody secreted by mucosal lymphoid tissues.


Immunology_Janeway

Immunology_Janeway. IgA Immunoglobulin class composed of α heavy chains that can occur in a monomeric and a polymeric (mainly dimeric) form. Polymeric IgA is the main antibody secreted by mucosal lymphoid tissues. IgA deficiency The class of immunoglobulin characterized by α heavy chains. It is the most common type of immunodeficiency. It can occur in a monomeric and a polymeric (mainly dimeric) form. Polymeric IgA is the main antibody secreted by mucosal lymphoid tissues. IgD Immunoglobulin class composed of δ heavy chains that appears as surface immunoglobulin on mature B cells. IgE Immunoglobulin class composed of ε heavy chains that acts in defense against parasite infections and in allergic reactions. IgG Immunoglobulin class composed of γ heavy chains that is the most abundant class of immunoglobulin in the plasma. IgM Immunoglobulin class composed of μ heavy chains that is the first to appear on B cells and the first to be secreted. IgNAR See immunoglobulin new antigen receptor.


Immunology_Janeway

Immunology_Janeway. IgM Immunoglobulin class composed of μ heavy chains that is the first to appear on B cells and the first to be secreted. IgNAR See immunoglobulin new antigen receptor. IgW Type of heavy-chain isotype present in cartilaginous fishes composed of six immunoglobulin domains. IKK The IkB kinase, IKK, is a multisubunit protein complex composed of IKKα, IKKβ, and IKKγ (or NEMO). IKKε A kinase that interacts with TBK1 (TANK-binding kinase 1) in the phosphorylation of IRF3 downstream of TLR-3 signaling. IL-1 family One of four major families of cytokines, this family contains 11 cytokines that are structurally similar to IL-1α, and are largely pro-inﬂammatory in function. IL-1β A cytokine produced by active macrophages that has many effects in the immune response, including the activation of vascular endothelium, activation of lymphocytes, and the induction of fever.


Immunology_Janeway

Immunology_Janeway. IL-1β A cytokine produced by active macrophages that has many effects in the immune response, including the activation of vascular endothelium, activation of lymphocytes, and the induction of fever. IL-6 Interleukin-6, a cytokine produced by activated macrophages and which has many effects, including lymphocyte activation, the stimulation of antibody production, and the induction of fever. IL-7 receptor (IL-7Rα) See CD127. IL-21 A cytokine produced by T cells (e.g.,TFH cells) that activates STAT3 and promotes survival and proliferation, particularly germinal center B cells. ILC1 A subset of innate lymphoid cells characterized by production of IFN-γ. ILCs (innate lymphoid cells) These are a class of innate immune cells having overlapping characteristics with T cells but lacking an antigen receptor. They arise in several groups, ILC1, ILC2, ILC3, and NK cells, which exhibit properties roughly similar to TH1, TH2, TH17, and CD8 T cells.


Immunology_Janeway

Immunology_Janeway. Imd (immunodeficiency) signaling pathway A defense against Gram-negative bacteria in insects that results in the production of antimicrobial peptides such as diptericin, attacin, and cecropin. imiquimod Drug (aldara) approved for treatment of basal cell carcinoma, genital warts, and actinic keratoses known to activate TLR-7, although not approved as an adjuvant for vaccines. immature B cells B cells that have rearranged a heavyand a light-chain V-region gene and express surface IgM, but have not yet matured sufficiently to express surface IgD as well. immediate hypersensitivity reactions Allergic reactions that occur within seconds to minutes of encounter with antigen, caused largely by activation of mast cells or basophils.


Immunology_Janeway

Immunology_Janeway. immediate hypersensitivity reactions Allergic reactions that occur within seconds to minutes of encounter with antigen, caused largely by activation of mast cells or basophils. immune complexes Complexes formed by the binding of antibody to its cognate antigen. Activated complement proteins, especially C3b, are often bound in immune complexes. Large immune complexes form when sufficient antibody is available to cross-link multivalent antigen; these are cleared by cells of the reticuloendothelial system that bear Fc receptors and complement receptors. Small, soluble immune complexes form when antigen is in excess; these can be deposited in small blood vessels and damage them. immune evasion Mechanisms used by pathogens to avoid detection and/ or elimination by host immune defenses. immune modulation The deliberate attempt to change the course of an immune response, for example by altering the bias toward TH1 or TH2 dominance.


Immunology_Janeway

Immunology_Janeway. immune modulation The deliberate attempt to change the course of an immune response, for example by altering the bias toward TH1 or TH2 dominance. immune surveillance The recognition, and in some cases the elimination, of tumor cells by the immune system before they become clinically detectable. immune system The tissues, cells, and molecules involved in innate immunity and adaptive immunity. immunodeficiency diseases Any inherited or acquired disorder in which some aspect or aspects of host defense are absent or functionally defective. immunodominant Describes epitopes in an antigen that are preferentially recognized by T cells, such that T cells specific for those epitopes come to dominate the immune response. immunoevasins Viral proteins that prevent the appearance of peptide:MHC class I complexes on the infected cell, thus preventing the recognition of virus-infected cells by cytotoxic T cells.


Immunology_Janeway

Immunology_Janeway. immunoevasins Viral proteins that prevent the appearance of peptide:MHC class I complexes on the infected cell, thus preventing the recognition of virus-infected cells by cytotoxic T cells. immunogenic Any molecule that, on its own, is able to elicit an adaptive immune response on injection into a person or animal. immunoglobulin (Ig) The protein family to which antibodies and B-cell receptors belong. immunoglobulin A (IgA) See IgA. immunoglobulin D (IgD) See IgD. immunoglobulin domain Protein domain first described in antibody molecules but present in many proteins. immunoglobulin E (IgE) See IgE. immunoglobulin fold The tertiary structure of an immunoglobulin domain, comprising a sandwich of two β sheets held together by a disulfide bond. immunoglobulin G (IgG) See IgG. immunoglobulin-like domain (Ig-like domain) Protein domain structurally related to the immunoglobulin domain.


Immunology_Janeway

Immunology_Janeway. immunoglobulin G (IgG) See IgG. immunoglobulin-like domain (Ig-like domain) Protein domain structurally related to the immunoglobulin domain. immunoglobulin-like proteins Proteins containing one or more immunoglobulin-like domains, which are protein domains structurally similar to those of immunoglobulins. immunoglobulin M (IgM) See IgM. immunoglobulin new antigen receptor (IgNAR) A form of heavy-chainonly Ig molecule made by shark species. immunoglobulin repertoire The variety of antigen-specific immunoglobulins (antibodies and B-cell receptors) present in an individual. Also known as the antibody repertoire. immunoglobulin superfamily Large family of proteins with at least one Ig or Ig-like domain, many of which are involved in antigen recognition and cell– cell interaction in the immune system and other biological systems.