Glossary

acquired immune response: Immunity mediated by lymphocytes and characterized by antigen specificity and memory.

acute phase proteins: Serum proteins, mostly produced in the liver, that rapidly change in concentration (some increase, some decrease) during the initiation of an inflammatory response.

addressin: Cell adhesion molecule present on the luminal surface of blood and lymph vessel endothelium, and recognized by homing molecules that direct leukocytes to tissues with the appropriate “address.”

adjuvant: Any substance that nonspecifically enhances the immune response to antigen.

affinity (intrinsic affinity): The strength of binding (affinity constant) between a receptor (e.g., one antigen-binding site on an antibody) and a ligand (e.g., epitope on an antigen).

affinity chromatography: The use of immobilized antibody (or antigen) to select specific antigen (or antibody) from a mixture. The purified ligand is then released by disrupting the antibody–antigen interaction, for example by changing the pH.

allele: Variants of a polymorphic gene at a given genetic locus.

allelic exclusion: The phenomenon whereby, following successful rearrangement of one allele of an antigen receptor gene, rearrangement of the other parental allele is suppressed.

allergen: An antigen that causes allergy.

allergy: IgE-mediated hypersensitivity (e.g., asthma, eczema, hayfever, and food allergy).

allogeneic: Refers to the genetic differences between individuals of the same species.

allograft: Tissue or organ graft between allogeneic individuals.

allotype: An allelic variant of an antigen that, because it is not present in all individuals, may be immunogenic in members of the same species that have a different version of the allele.

alternative pathway (of complement activation): Activation pathway involving complement components C3, factor B, factor D, and properdin that, in the presence of a stabilizing activator surface such as microbial polysaccharide, generates the alternative pathway C3 convertase C3bBb.

anaphylatoxin: A substance (e.g., C3a, C4a, or C5a) capable of directly triggering mast cell degranulation.

anaphylaxis: An often fatal hypersensitivity reaction, triggered by IgE or anaphylatoxin-mediated mast cell degranulation, leading to anaphylactic shock due to vasodilatation and smooth muscle contraction.

anergy: Potentially reversible specific immunological tolerance in which the lymphocyte becomes functionally nonresponsive.

antibody-dependent cellular cytotoxicity (ADCC): A cytotoxic reaction in which an antibody-coated target cell is directly killed by an Fc receptor-bearing leukocyte (e.g., NK cell, macrophage, or neutrophil).

antigen: Any molecule capable of being recognized by an antibody or T-cell receptor.

antigenic determinant: A cluster of epitopes (see epitope).

antigen-presenting cell (APC): A term most commonly used when referring to cells that present processed antigenic peptide and MHC class II molecules to the T-cell receptor on CD4⁺ T-cells (e.g., dendritic cells, macrophages, B-cells). Note, however, that most types of cell are able to present antigenic peptides with MHC class I to CD8⁺ T-cells (e.g., as occurs with virally infected cells).

apoptosis: A form of programmed cell death characterized by endonuclease digestion of DNA.

atopic allergy: IgE-mediated hypersensitivity (e.g., asthma, eczema, hayfever, and food allergy).

autologous: From the same individual.

avidity (functional affinity): The binding strength between two molecules (e.g., antibody and antigen) taking into account the valency of the interaction. Thus the avidity will always be equal to or greater than the intrinsic affinity (see affinity).

basophil: A type of granulocyte found in the blood and resembling the tissue mast cell.

BCG (bacille Calmette–Guérin): Attenuated Mycobacterium tuberculosis, used both as a specific vaccine for tuberculosis and as an adjuvant.

β₂-microglobulin: A 12 kDa protein, not itself encoded within the MHC, but forming part of the structure of MHC class I-encoded molecules.

biolistics: The use of small particles (e.g., colloidal gold) as a vehicle for carrying agents (drugs, nucleic acid, etc.) into a cell. Following coating with the desired agent(s), the particles are fired into the dermis of the recipient using a helium-powered gun.

bispecific antibody: An artificially produced hybrid antibody in which each of the two antigen-binding arms is specific for a different antigenic epitope. Such antibodies, which can be produced either by chemical cross-linkage or by recombinant DNA techniques, can be used to link together two different antigens or cells (e.g., a cytotoxic T-cell and a tumor cell).

B-1/B-2-cells: The two major subpopulations of B-lymphocytes. B-1 cells bear high levels of surface IgM, lower levels of surface IgD, are CD43⁺ CD23⁻ and most express the cell surface antigen CD5; they are self-renewing, and frequently secrete high levels of antibody, which binds to a range of antigens (“polyspecificity”) with a relatively low affinity. The majority of B-cells, however, are B-2, which express low levels of surface IgM, higher levels of surface IgD, do not express CD5, and are CD43⁻ CD23⁺; they are directly generated from precursors in the bone marrow and secrete highly specific antibody.

bursa of Fabricius: A primary lymphoid organ in avian species, located at the cloacal–hind gut junction; it is the site of B-cell maturation.

capping: An active process whereby cross‐linking of cell surface molecules (e.g., by antibody) leads to aggregation and subsequent migration of the molecules to one pole of the cell.

carrier: Any molecule that when conjugated to a nonimmunogenic molecule (e.g., a hapten) makes the latter immunogenic by providing epitopes for helper T‐cells which the hapten lacks.

caspases: A family of cysteine proteases involved in generating apoptosis.

CD antigen: Cluster of differentiation designation assigned to leukocyte cell surface molecules that are identified by a given group of monoclonal antibodies.

CD3: A trimeric complex of γ, δ, and ε chains that together with a ζζ homodimer or ζη heterodimer acts as a signal transducing unit for the T‐cell receptor.

CD4: Cell surface glycoprotein, usually on helper T‐cells, that recognizes MHC class II molecules on antigen‐presenting cells.

CD8: Cell surface glycoprotein, usually on cytotoxic T‐cells, that recognizes MHC class I molecules on target cells.

cell‐mediated immunity (CMI): Refers to T‐cell‐mediated immune responses.

central memory: Immunological memory that is dependent on CCR7⁺ T‐cells that, under the influence of chemokines, travel to secondary lymphoid organs where they give rise to CCR7⁻ effector memory T‐cells.

central tolerance: Specific immunological tolerance due to the induction of lymphocyte apoptosis or anergy within the primary lymphoid organs (bone marrow in the case of B‐cell tolerance and the thymus for T‐cells).

chemokines: A family of structurally related cytokines that selectively induce chemotaxis and activation of leukocytes. They also play important roles in lymphoid organ development, cell compartmentalization within lymphoid tissues, Th1/Th2 development, angiogenesis, and wound healing.

chemotaxis: Movement of cells up a concentration gradient of chemotactic factors.

chimeric: Composite of genetically distinct individuals (e.g., following an allogeneic bone marrow graft).

citrullination: The enzymatic conversion, by peptidyl arginine deiminase, of an arginine in a protein to a citrulline.

classical pathway (of complement activation): Activation pathway involving complement components C1, C2, and C4 that, following fixation of C1q (e.g., by antigen–antibody complexes), produces the classical pathway C3 convertase C .

class switching: The process by which a B‐cell changes the class but not specificity of a given antibody it produces (e.g., switching from an IgM to an IgG antibody).

class switch recombination: The recombination of immunoglobulin heavy chain constant region gene segments (e.g., switching from Cμ and Cδ to Cγ1 to convert an IgM (and IgD) antibody into an IgG1 antibody).

clonal deletion: A process by which contact with antigen (e.g., self antigen) at an early stage of lymphocyte differentiation leads to cell death by apoptosis.

clonal selection: The selection and activation by antigen of a lymphocyte bearing a complementary receptor, which then proliferates to form an expanded clone.

clone: Identical cells derived from a single progenitor.

colony‐stimulating factors (CSF): Factors that permit the proliferation and differentiation of hematopoietic cells.

combinatorial diversity: That component of antibody and T‐cell receptor (TCR) diversity that is generated by the recombination of variable (V), diversity (D, for immunoglobulin heavy chains, and for TCR β and δ chains), and joining (J) gene segments.

complement: A group of serum proteins, some of which act in an enzymatic cascade, producing effector molecules involved in inflammation (C3a, C5a), phagocytosis (C3b), and cell lysis (C5b–9).

complementarity determining regions (CDR): The hypervariable amino acid sequences within antibody and T‐cell receptor variable regions that interact with complementary amino acids on the antigen or peptide–MHC complex.

ConA (concanavalin A): A T‐cell mitogen.

congenic: Animals that only differ only at a single genetic locus.

conjugate: Covalently linked complex of two or more molecules (e.g., fluorescein conjugated to antibody).

convergent evolution: Independent evolution of similarity between molecules or between species.

Coombs’ test: Diagnostic test using anti‐immunoglobulin to agglutinate antibody‐coated erythrocytes.

cortex: Outer (peripheral) layer of an organ.

C‐reactive protein: An acute phase protein that is able to bind to the surface of microorganisms where it functions as a stimulator of the classical pathway of complement activation, and as an opsonin for phagocytosis.

cyclophosphamide: Cytotoxic drug used as an immunosuppressive.

cyclosporine: A T‐cell‐specific immunosuppressive drug used to prevent graft rejection.

cytokines: Low‐molecular‐weight proteins that stimulate or inhibit the differentiation, proliferation or function of immune cells.

cytophilic: Binds to cells.

cytotoxic: Kills cells.

cytotoxic T‐lymphocyte (CTL, Tc): T‐cells (usually CD8⁺) that kill target cells following recognition of foreign peptide–MHC molecules on the target cell membrane.

danger-associated molecular pattern (DAMP): A structure or molecule produced by necrotic cells and which provides danger signals to activate the immune response following tissue damage.

defensins: A family of small basic antimicrobial peptides, produced by both animals and plants.

delayed-type hypersensitivity (DTH): A hypersensitivity reaction occurring within 48–72 hours and mediated by cytokine release from sensitized T-cells.

dendritic cell (DC): Refers to an interdigitating dendritic cell that is MHC class II positive and presents processed antigens to T-cells in the T-cell areas of secondary lymphoid tissues. (Note: This is a different cell type to follicular dendritic cells.)

differential splicing: The utilization and splicing of different exons from a primary RNA transcript in order to generate different mRNA sequences.

differentiation antigen: A cell surface molecule expressed at a particular stage of development or on cells of a given lineage.

DiGeorge syndrome: Immunodeficiency caused by a congenital failure in thymic development resulting in a lack of mature functional T-cells.

diversity (D) gene segments: Found in the immunoglobulin heavy chain gene and T-cell receptor β and δ gene loci between the V and J gene segments. They encode part of the third hypervariable region (CDR3) in these antigen receptor chains.

domain: A structural element of a polypeptide.

edema: Swelling caused by accumulation of fluid in the tissues.

effector cells: Cells that carry out an immune function (e.g., cytokine release, cytotoxicity).

ELISA (enzyme-linked immunosorbent assay): Assay for detection or quantitation of an antibody or antigen using a ligand (e.g., an anti-immunoglobulin) conjugated to an enzyme that changes the color of a substrate.

endocytosis: Cellular ingestion of macromolecules by invagination of plasma membrane to produce an intracellular vesicle that encloses the ingested material.

endogenous: From within.

endosomes: Intracellular smooth-surfaced vesicles in which endocytosed material passes on its way to the lysosomes.

endotoxin: Pathogenic cell wall-associated lipopolysaccharides of Gram-negative bacteria.

eosinophil: A class of granulocyte, the granules of which contain toxic cationic proteins.

epitope: That part of an antigen recognized by an antigen receptor (see antigenic determinant).

Epstein–Barr virus (EBV): The virus responsible for infectious mononucleosis and Burkitt’s lymphoma. Can be used to immortalize human B-cells in vitro.

equivalence: The ratio of antibody to antigen at which immunoprecipitation of the reactants is virtually complete.

erythema: The redness produced during inflammation due to erythrocytes entering tissue spaces.

erythropoiesis: Erythrocyte production.

exotoxin: Pathogenic protein secreted by bacteria.

exudate: The extravascular fluid (containing proteins and cellular debris) that accumulates during inflammation.

Fab: Monovalent antigen-binding fragment obtained following papain digestion of immunoglobulin. Consists of an intact light chain and the N-terminal V_H and C_H1 domains of the heavy chain.

F(ab′)₂ : Bivalent antigen-binding fragment obtained following pepsin digestion of immunoglobulin. Consists of both light chains and the N-terminal part of both heavy chains linked by disulfide bonds.

Fas: A member of the TNF receptor gene family. Engagement of Fas (CD95) on the surface of the cell by the Fas ligand (CD178) present on cytotoxic cells can trigger apoptosis in the Fas-bearing target cell.

Fc: Crystallizable, nonantigen-binding fragment of an immunoglobulin molecule obtained following papain digestion. Consists of the C-terminal portion of both heavy chains that is responsible for binding to Fc receptors and C1q.

Fc receptors: Cell surface receptors that bind the Fc portion of particular immunoglobulin classes.

fibroblast: Connective tissue cell that produces collagen and plays an important part in wound healing.

fluorescein isothiocyanate (FITC): Green fluorescent dye used to “tag” antibodies for use in immunofluorescence.

fluorescent antibody: An antibody conjugated to a fluorescent dye such as FITC.

foam cell: Macrophages that have engulfed low-density lipoproteins. They are characteristically present in atherosclerotic plaques.

follicular dendritic cell: MHC class II-negative Fc receptor-positive dendritic cells that bear immune complexes on their surface and are involved in the stimulation of B-cells and maintenance of B-cell memory in germinal centers. (Note: This is a different cell type to interdigitating dendritic cells).

follicular helper T-cell: Subset of helper T-cells that direct B-cell development, class switch recombination and survival within germinal centers.

Foxp3: A transcription factor present in the nucleus of most regulatory T-cells.

framework regions: The relatively conserved amino acid sequences that flank the hypervariable regions in immunoglobulin and T-cell receptor variable regions and maintain a common overall structure for all V-region domains.

Freund’s adjuvant: Complete Freund’s adjuvant is an emulsion of aqueous antigen in mineral oil that contains heat-killed mycobacteria. Incomplete Freund’s adjuvant lacks the mycobacteria.

Fv: The variable region fragment of an antibody heavy or light chain.

γ-globulin: The serum proteins, mostly immunoglobulins, which have the greatest mobility towards the cathode during electrophoresis.

germinal center: Discrete areas within secondary lymphoid tissues where B-cell maturation and memory development occur.

germline: The arrangement of the genetic material as transmitted through the gametes.

giant cell: Large multinucleate cell derived from fused macrophages and often present in granulomas.

glomerulonephritis: Inflammation of renal glomerular capillary loops, often resulting from immune complex deposition.

graft-versus-host (GVH) reaction: Reaction occurring when T-lymphocytes present in a graft recognize and attack host cells.

granulocyte: Myeloid cells containing cytoplasmic granules (i.e., neutrophils, eosinophils, and basophils).

granuloma: A tissue nodule containing proliferating lymphocytes, fibroblasts, and giant cells and epithelioid cells (both derived from activated macrophages), which forms due to inflammation in response to chronic infection or persistence of antigen in the tissues.

granzymes: Serine esterases present in the granules of cytotoxic T-lymphocytes and NK cells. They induce apoptosis in the target cell that they enter through perforin channels inserted into the target cell membrane by the cytotoxic cell.

gut-associated lymphoid tissue (GALT): Includes Peyer’s patches, appendix, and solitary lymphoid nodules in the submucosa.

haplotype: The set of allelic variants present at a given genetic region.

hapten: A low-molecular-weight molecule that is recognized by preformed antibody but is not itself immunogenic unless conjugated to a “carrier” molecule that provides epitopes recognized by helper T-cells.

helper T-lymphocyte (Th): A subclass of T-cells that provide help (in the form of cytokines and/or cognate interactions) necessary for the expression of effector function by other cells in the immune system.

hemagglutinin: Any molecule that agglutinates erythrocytes.

hematopoiesis: The production of erythrocytes, leukocytes, and platelets.

hematopoietic stem cells: Self-renewing stem cells that are capable of giving rise to all of the formed elements of the blood (i.e., leukocytes, erythrocytes, and platelets).

heterozygous: Possessing different alleles at a given locus on the two homologous chromosomes.

high endothelial venule (HEV): Capillary venule composed of specialized endothelial cells allowing migration of lymphocytes into lymphoid organs.

hinge region: Amino acids between the Fab and Fc regions of immunoglobulin that permit flexibility of the molecule.

histamine: Vasoactive amine present in basophil and mast cell granules that, following degranulation, causes increased vascular permeability and smooth muscle contraction.

HLA (human leukocyte antigen): The human major histocompatibility complex (MHC).

homing receptors: Cell surface molecules that direct leukocytes to specific locations in the body.

homozygous: Possessing the same allele at a given locus on the two homologous chromosomes.

H-2: The mouse major histocompatibility complex (MHC).

humanized antibody: A genetically engineered monoclonal antibody of nonhuman origin in which all but the antigen-binding CDR sequences have been replaced with sequences derived from human antibodies. This procedure is carried out to minimize the immunogenicity of therapeutic monoclonal antibodies.

humoral: Pertaining to extracellular fluid such as plasma and lymph. The term humoral immunity is used to denote antibody-mediated immune responses.

hybridoma: Hybrid cell line obtained by fusing a lymphoid tumor cell with a lymphocyte that then has both the immortality of the tumor cell and the effector function (e.g., monoclonal antibody secretion) of the lymphocyte.

hypersensitivity: Excessive immune response that leads to undesirable consequences (e.g., tissue or organ damage).

hypervariable regions: Those amino acid sequences within the immunoglobulin and T-cell receptor variable regions that show the greatest variability and contribute most to the antigen or peptide–MHC binding site.

idiotope: An epitope made up of amino acids within the variable region of an antibody or T-cell receptor that reacts with an anti-idiotope.

idiotype: The complete set of idiotopes in the variable region of an antibody or T-cell receptor that react with an anti-idiotypic serum.

idiotype network: A regulatory network based on interactions of idiotypes and anti-idiotypes present on antibodies and T-cell receptors.

immune complex: Complex of antibody bound to antigen that may also contain complement components.

immunoadsorption: Method for removal of antibody or antigen by allowing it to bind to solid phase antigen or antibody.

immunofluorescence: Technique for detection of cell- or tissue-associated antigens by the use of a fluorescently tagged ligand (e.g., an anti-immunoglobulin conjugated to fluorescein isothiocyanate).

immunogen: Any substance that elicits an immune response. Although all immunogens are antigens, not all antigens are immunogens (see hapten).

immunoglobulin superfamily: Large family of proteins characterized by possession of “immunoglobulin-type” domains of approximately 110 amino acids folded into two β-pleated sheets. Members include immunoglobulins, T-cell receptors, and MHC molecules.

immunological synapse: A contact point between the T-cell and antigen-presenting cell that is generated by reorganization and clustering of cell surface molecules in lipid rafts. The synapse facilitates interactions between TCR and MHC, co-stimulatory and adhesion molecules, thereby potentiating the TCR-mediated activation signal.

immunotoxin: A biochemical conjugate, or recombinant fusion protein, consisting of an immune targeting molecule such as an antibody or antibody fragment together with a cytotoxic molecule.

inflammasome: A multi-protein cytoplasmic complex that promotes inflammation by converting the IL-1β precursor into active IL-1β, and additionally by stimulating the generation of IL-18.

inflammation: The tissue response to trauma, characterized by increased blood flow and entry of leukocytes into the tissues, resulting in swelling, redness, elevated temperature, and pain.

innate immunity: Immunity that is not intrinsically affected by prior contact with antigen (i.e., all aspects of immunity not directly mediated by lymphocytes).

integrins: A family of heterodimeric cell adhesion molecules.

interdigitating dendritic cell: MHC class II-positive antigen-presenting dendritic cell found in T-cell areas of lymph nodes and spleen. (Note: This is a different cell type to follicular dendritic cells.)

interferons (IFN): IFNα and IFNβ (type I interferons) can be induced in most cell types, whereas IFNγ (type II interferon) is produced by T-lymphocytes and NK cells. All three types induce an antiviral state in cells and IFNγ additionally acts in the regulation of immune responses.

interleukins (IL): Designation for some of the cytokines secreted by leukocytes.

internal image: An epitope on an anti-idiotype that binds in a way that structurally and functionally mimics the antigen.

invariant chain: A polypeptide that binds MHC class II molecules in the endoplasmic reticulum, directs them to the late endosomal compartment and prevents premature association with self peptides.

Ir (immune response) genes: The genes, including those within the MHC, that together determine the overall level of immune response to a given antigen.

isotype: An antibody constant region structure present in all normal individuals (i.e., antibody class or subclass).

ITAM: Immunoreceptor tyrosine-based activation motifs are amino acid consensus sequences recognized by src-family tyrosine kinases. These motifs are found in the cytoplasmic domains of several signaling molecules including the signal transduction units of lymphocyte antigen receptors and of Fc receptors.

ITIM: Immunoreceptor tyrosine-based inhibitory motifs present in the cytoplasmic domains of certain cell surface molecules (e.g., FcγRIIB, inhibitory NK cell receptors), and that mediate inhibitory signals.

J chain: A molecule that forms part of the structure of pentameric IgM and dimeric IgA.

joining (J) gene segments: Found in the immunoglobulin and T-cell receptor gene loci and, upon gene rearrangement, encode part of the third hypervariable region (CDR3) of the antigen receptors.

junctional diversity: Diversity of the splice junctions in the recombined variable (V), diversity (D, for immunoglobulin heavy chains, and for TCR β and δ chains), and joining (J) gene segments of antibody and T-cell receptor (TCR) genes.

K (killer) cell: A generic term for any leukocyte that mediates antibody-dependent cellular cytotoxicity (ADCC).

kinins: A family of polypeptides released during inflammatory responses and that increase vascular permeability and smooth muscle contraction.

KIRs: Killer cell immunoglobulin-like receptors found on NK cells, some γδ and some αβ T-cells. KIRs recognize MHC class I molecules and, like the C-type lectin receptors also found on these cells, can either inhibit or activate the killer cells. If ITIM sequences are present in their cytoplasmic domain they are inhibitory. KIRs lacking ITIMs can associate with ITAM-containing adaptor molecules, in which case they can activate the NK cell or T-cell.

knockout: The use of homologous genetic recombination in embryonal stem cells to replace a functional gene with a defective copy of the gene. The animals that are produced by this technique can be bred to homozygosity, thus allowing the generation of a null phenotype for that gene product.

Kuppfer cells: Fixed tissue macrophages lining the blood sinuses in the liver.

lamina propria: The connective tissue underlying the epithelium at mucosal sites.

Langerhans cell: Fc receptor and MHC class II-positive antigen-presenting dendritic cell found in the skin.

large granular lymphocyte (LGL): Leukocytes (most are not actually true lymphocytes) that contain cytoplasmic granules and function as natural killer (NK) and killer (K) cells. Activated CD8⁺ cytotoxic T-lymphocytes (Tc) also assume an LGL morphology.

lectins: A family of proteins that bind specific sugars on glycoproteins and glycolipids. Some plant lectins are mitogenic (e.g., PHA, ConA).

leukocyte: White blood cells, which include neutrophils, basophils, eosinophils, lymphocytes, NK cells, and monocytes.

leukotrienes: Metabolic products of arachidonic acid that promote inflammatory processes (e.g., chemotaxis, increased vascular permeability) and are produced by a variety of cell types including mast cells, basophils, and macrophages.

ligand: General term for a molecule recognized by a binding structure such as a receptor.

linkage disequilibrium: The occurrence of two alleles being inherited together at a greater frequency than that expected from the product of their individual frequencies.

lipid raft: Cholesterol- and glycosphingolipid-rich membrane subdomain in which molecules involved in cellular activation become concentrated.

lipopolysaccharide (LPS): Endotoxin derived from Gram-negative bacterial cell walls that has inflammatory and mitogenic actions.

lymph: The tissue fluid that drains into and through the lymphatic system.

lymphadenopathy: Enlarged lymph nodes.

lymphotoxin (also called TNFβ): A T-cell-derived cytokine that is cytotoxic for certain tumor cells and also has immunoregulatory functions.

lysosomes: Membrane-bound cytoplasmic organelles containing hydrolytic enzymes involved in the digestion of phagocytosed material.

lysozyme: Antibacterial enzyme present in phagocytic cell granules, tears, and saliva, which digests peptidoglycans in bacterial cell walls.

macrophage: Large phagocytic cell, derived from the blood monocyte, which also functions as an antigen-presenting cell and can mediate ADCC.

mannose binding lectin (mannose binding protein): A member of the collectin family of calcium-dependent lectins, and an acute phase protein. It functions as a stimulator of the lectin pathway of complement activation, and as an opsonin for phagocytosis by binding to mannose, a sugar residue usually found in an exposed form only on the surface of microorganisms.

marginal zone: The outer area of the splenic periarteriolar lymphoid sheath (PALS) that is rich in B-cells, particularly those responding to thymus-independent antigens.

margination: Leukocyte adhesion to the endothelium of blood vessels in the early phase of an acute inflammatory reaction.

mast cell: A tissue cell with abundant granules that resembles the blood basophil. Both these cell types bear high-affinity Fc receptors for IgE, which when cross-linked by IgE and antigen cause degranulation and the release of a number of mediators including histamine and leukotrienes.

medulla: Inner (central) region of an organ.

megakaryocyte: A bone marrow precursor of platelets.

membrane attack complex (MAC): Complex of complement components C5b–C9 that inserts as a pore into the membrane of target cells, leading to cell lysis or apoptosis.

memory (immunological): A characteristic of the acquired immune response of lymphocytes whereby a second encounter with a given antigen produces a secondary immune response, which is faster, greater, and longer lasting than the primary immune response.

memory cells: Clonally expanded T- and B-cells produced during a primary immune response and that are “primed” to mediate a secondary immune response to the original antigen.

MHC (major histocompatibility complex): A genetic region encoding molecules involved in antigen presentation to T-cells. Class I MHC molecules are present on virtually all nucleated cells and are encoded mainly by the H-2 K, H-2D, and H-2 L loci in mice and by HLA-A, HLA-B, and HLA-C in humans, while class II MHC molecules are expressed on antigen-presenting cells (primarily dendritic cells, macrophages, and B-cells) and are encoded by H-2A and H-2E in mice and HLA-DR, HLA-DQ, and HLA-DP in humans. Allelic differences are associated with the most intense graft rejection within a species.

MHC restriction: The necessity that T-cells recognize processed antigen only when presented by MHC molecules of the original haplotype associated with T-cell priming.

minor histocompatibility antigens: Non-MHC-encoded processed peptides derived from the allogeneic products of polymorphic gene loci. In association with MHC-encoded molecules they contribute to graft rejection, albeit not usually as severe as that due to MHC mismatch.

mitogen: A substance that nonspecifically induces lymphocyte proliferation.

mixed lymphocyte reaction (MLR): A T-cell proliferative response induced by cells expressing allogeneic MHC.

monoclonal antibody: Homogeneous antibody derived from a single B-cell clone and therefore all bearing identical antigen-binding sites and isotype.

monocyte: Mononuclear phagocyte found in blood and that is the precursor of the tissue macrophage.

mononuclear phagocyte system: A system comprising blood monocytes and tissue macrophages.

mucosa-associated lymphoid tissue (MALT): Lymphoid tissue present in the surface mucosa of the respiratory, gastrointestinal, and genitourinary tracts.

multiple myeloma: Plasma cell malignancy resulting in high levels of monoclonal immunoglobulin in serum and of free light chains (Bence Jones protein) in urine.

murine: Pertaining to mice.

myeloma protein: Monoclonal antibody secreted by myeloma cells.

naive lymphocyte: A mature T- or B-cell that has not yet been activated by initial encounter with antigen.

negative selection: Deletion by apoptosis in the thymus of T-cells that recognize self peptides presented by self MHC molecules, thus preventing the development of autoimmune T-cells. Negative selection of developing B-cells also occurs if they encounter high levels of self antigen in the bone marrow.

neutrophil: The major circulating phagocytic polymorphonuclear granulocyte. Enters tissues early in an inflammatory response and is also able to mediate antibody-dependent cellular cytotoxicity (ADCC).

NK (natural killer) cell: Large granular leukocyte that does not rearrange nor express either immunoglobulin or T-cell receptor genes but is able to recognize and destroy certain tumor and virally infected cells in an MHC- and antibody-independent manner. Also able to mediate ADCC.

NKT cell: NK1.1⁺ lymphoid cells with a morphology and granule content intermediate between T-cells and NK cells. They express low levels of αβ TCR with an invariant α chain and very restricted β chain specificity, recognize lipid and glycolipid antigens presented by the nonclassical MHC-like molecule CD1d, and are potent producers of IL-4 and IFNγ.

N-nucleotides: Nontemplated nucleotides added to the junctions between antibody and T-cell receptor variable (V), diversity (D), and joining (J) gene segments during gene rearrangement.

NOD-like receptor: A family of cytoplasmic pattern recognition receptors involved in sensing the presence of pathogens.

nude mouse: Mouse that is T-cell deficient due to a homozygous gene defect (nu/nu) resulting in the absence of a thymus (and also lack of body hair).

oligoclonal: A few different clones, or the product of a few different clones.

oncofetal antigen: Antigen whose expression is normally restricted to the fetus but that may be expressed during malignancy in adults.

opsonin: Substance (e.g., antibody or C3b) that enhances phagocytosis by promoting adhesion of the antigen to the phagocyte.

opsonization: Coating of antigen with opsonin to enhance phagocytosis.

PAF (platelet activating factor): An alkyl phospholipid released by a variety of cell types including mast cells and basophils, which has immunoregulatory effects on lymphocytes and monocytes/macrophages as well as causing platelet aggregation and degranulation.

paracortex: The part of an organ (e.g., lymph node) that lies between the cortex and the medulla.

pathogen-associated molecular pattern (PAMP): Molecules such as lipopolysaccharide, peptidoglycan, lipoteichoic acids, and mannans, which are widely expressed by microbial pathogens as repetitive motifs but are not present on host tissues. They are therefore utilized by the pattern recognition receptors (PRRs) of the immune system to distinguish pathogens from self antigens.

pattern recognition receptor (PRR): Cell-associated or soluble receptors that enable the immune system to detect pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs). Among the large number of different PRRs are the mannose receptor (CD206), macrophage scavenger receptor (CD204), and the Toll-like receptors.

perforin: Molecule produced by cytotoxic T-cells and NK cells that, like complement component C9, polymerizes to form a pore in the membrane of the target cell leading to cell death.

periarteriolar lymphoid sheath (PALS): The lymphoid tissue that forms the white pulp of the spleen.

peripheral tolerance: Specific immunological tolerance occurring outside of the primary lymphoid organs.

Peyer’s patches: Part of the gut-associated lymphoid tissue (GALT) and found as distinct lymphoid nodules mainly in the small intestine.

PHA (phytohemagglutinin): A plant lectin that acts as a T-cell mitogen.

phage antibody library: A collection of cloned antibody variable region gene sequences that can be expressed as Fab or scFv fusion proteins with bacteriophage coat proteins. These can be displayed on the surface of the phages. The gene encoding a monoclonal recombinant antibody is enclosed in the phage particle and can be selected from the library by binding of the phage to specific antigen.

phagocyte: Cells (including monocytes/macrophages and neutrophils) that are specialized for the engulfment of cellular and particulate matter.

phagolysosome: Intracellular vacuole where killing and digestion of phagocytosed material occurs following the fusion of a phagosome with a lysosome.

phagosome: Intracellular vacuole produced following invagination of the cell membrane around phagocytosed material.

phorbol myristate acetate (PMA): A mitogenic phorbol ester that directly stimulates protein kinase C and acts as a tumor promoter.

plaque-forming cell (PFC): Antibody-secreting plasma cell detected in vitro by its ability to produce a “plaque” of lysed antigen-sensitized erythrocytes in the presence of complement.

plasma cell: Terminally differentiated B-lymphocyte that actively secretes large amounts of antibody.

pluripotent stem cell: A cell that has the potential to differentiate into many different cell types.

P-nucleotides: Palindromic nucleotide sequences generated at the junctions between antibody and T-cell receptor variable (V), diversity (D), and joining (J) gene segments during gene rearrangement.

pokeweed mitogen (PWM): A plant lectin that is a T-cell-dependent B-cell mitogen.

polyclonal: Many different clones, or the product of many different clones (e.g., polyclonal antiserum).

poly-Ig receptor: A receptor molecule that specifically binds J-chain containing polymeric Ig (i.e., dimeric secretory IgA and pentameric IgM) and transports it across mucosal epithelium.

polymorphic: Highly variable in structure or sequence.

positive selection: The selection of those developing T-cells in the thymus that are able to recognize self MHC molecules. This occurs by preventing apoptosis in these cells.

precipitin: Precipitate of antibody and multivalent antigen due to the formation of high molecular weight complexes.

primary immune response: The relatively weak immune response that occurs upon the first encounter of naive lymphocytes with a given antigen.

primary lymphoid organs: The sites at which immunocompetent lymphocytes develop (i.e., bone marrow and thymus in mammals).

prime: The process of giving an initial sensitization to antigen.

prostaglandins: Acidic lipids derived from arachidonic acid that are able to increase vascular permeability, mediate fever, and can both stimulate and inhibit immunological responses.

proteasome: Cytoplasmic proteolytic enzyme complex involved in antigen processing to generate peptides for association with MHC.

protein A:Staphylococcus aureus cell wall protein that binds to the Fc region of IgG.

protein tyrosine kinases: Enzymes that are able to phosphorylate proteins on tyrosines, and often act in a cascade-like fashion in the signal transduction systems of cells.

Qa antigens: “Nonclassical” MHC class I molecules of mice.

radioimmunoconjugate: A biochemical conjugate consisting of an immune targeting molecule such as an antibody or antibody fragment together with a cytotoxic radionuclide.

recombination signal sequence (RSS): Conserved heptamer (7-nucleotide)-nonamer (9-nucleotide) sequences, separated by a 12 or 23 base spacer, which occur 3′ of variable gene segments, 5′ and 3′ of diversity gene segments, and 5′ of joining gene segments, in both immunoglobulin and T-cell receptor genes. They function as recognition sequences for the recombinase enzymes that mediate the gene rearrangement process involved in the generation of lymphocyte antigen receptor diversity.

regulatory idiotope: An antibody or T-cell receptor idiotope capable of regulating immune responses via interaction with lymphocytes bearing complementary idiotopes (anti-idiotopes).

regulatory T-cell: T-cells, mostly CD4⁺, that suppress the functional activity of lymphocytes and dendritic cells.

respiratory burst: The increased oxidative metabolism that occurs in phagocytic cells following activation.

reticuloendothelial system (RES): A rather old term for the network of phagocytes and endothelial cells throughout the body.

rheumatoid factor: IgM, IgG, and IgA autoantibodies to the Fc region of IgG.

rosette: Particles or cells bound to the surface of a lymphocyte (e.g., sheep erythrocytes around a human T-cell).

scavenger receptors: Cell surface receptors, for example on phagocytic cells, that recognize cells or molecules that require clearance from the body.

scFv: A single-chain molecule composed of the variable regions of an antibody heavy and light chain joined together by a flexible linker.

SCID (severe combined immunodeficiency): Immunodeficiency affecting both T- and B-lymphocytes.

secondary immune response: The qualitatively and quantitatively improved immune response that occurs upon the second encounter of primed lymphocytes with a given antigen.

secretory component: Proteolytic cleavage product of the poly-Ig receptor that remains associated with dimeric IgA in sero-mucous secretions.

secretory IgA: Dimeric IgA found in sero-mucous secretions.

somatic hypermutation: The enhanced occurence of point mutations in the recombined immunoglobulin variable region V(D)J genes that occurs following antigenic stimulation and acts as a mechanism for increasing antibody diversity and affinity.

stem cell: Multipotential cell from which differentiated cells derive.

stochastic: A process involving at least some element of randomness.

superantigen: An antigen that reacts with all the lymphocytes belonging to a particular T-cell receptor or immunoglobulin V region family, and that therefore stimulates (or deletes) a much larger number of cells than does conventional antigen.

surface plasmon resonance: A technique based upon changes in the angle of reflected light that occur upon ligand binding to an immobilized target molecule on a biosensor chip. This permits the observation of protein–protein interactions (such as antibody binding to an antigen) in “real-time” (i.e., by continuous monitoring of the association and dissociation of the reversible reaction).

switch sequences: Highly conserved repetitive sequences that mediate class switching in the immunoglobulin heavy chain gene locus.

syngeneic: Genetically identical (e.g., a fully inbred strain of mice).

systemic: Throughout the body.

TAP: The transporters associated with antigen processing (TAP-1 and TAP-2) are molecules that carry antigenic peptides from the cytoplasm into the lumen of the endoplasmic reticulum for incorporation into MHC class I molecules.

T-cell receptor (TCR): The heterodimeric antigen receptor of the T-lymphocyte exists in two alternative forms, consisting of α and β chains, or γ and δ chains. The αβ TCR recognizes peptide fragments of protein antigens presented by MHC molecules on cell surfaces. The function of the γδ TCR is less clearly defined but it can often recognize native proteins on the cell surface.

T-dependent antigen: An antigen that requires helper T-cells in order to elicit an antibody response.

thymocyte: Developing T-cell in the thymus.

T-independent antigen: An antigen that is able to elicit an antibody response in the absence of T-cells.

titer: Measure of the relative “strength” (a combination of amount and avidity) of an antibody or antiserum, usually given as the highest dilution that is still operationally detectable in, for example, an ELISA.

tolerance: Specific immunological unresponsiveness.

tolerogen: An antigen used to induce tolerance. Often depends more on the circumstances of administration (e.g., route and concentration) than on any inherent property of the molecule.

Toll-like receptors (TLRs): A family of pattern recognition receptors involved in the detection of structures associated with pathogens or damaged host tissues.

toxoid: Chemically or physically modified toxin that is no longer harmful but retains immunogenicity.

tumor antigens: Antigens whose expression is associated with tumor cells.

tumor necrosis factor (TNF, also called TNFα): Together with the related cytokine lymphotoxin (TNFβ), was originally named for its cytotoxic effect on certain tumor cells, but also has important inflammatory and immunoregulatory functions.

variable (V) gene segments: Genes that rearrange together with D (diversity) and J (joining) gene segments in order to encode the variable region amino acid sequences of immunoglobulins and T-cell receptors.

vascular addressins: Cell adhesion molecules present on the luminal surface of blood and lymph vessel endothelium recognized by homing molecules that direct leukocytes to tissues with the appropriate “address.”

vasoactive amines: Substances including histamine and 5-hydroxytryptamine that increase vascular permeability and smooth muscle contraction.

xenogeneic: Genetic differences between species.

xenograft: A tissue or organ graft between individuals of different species.