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Immunology
A Short Course, Fourth Edition

Eli Benjamini, Richard Coico, and Geoffrey Sunshine

Paper • February 2000 • 500 pp. • 0-471-34890-2

Glossary

- Last Updated: June 11, 2002

a-fetoprotein: A principal plasma protein in the a globulin fraction present in the fetus. Patients with liver cancer patients reveal significantly elevated serum levels of a-fetoprotein.
accessory cell: A cell required to initiate immune response, often used to describe antigen-presenting cell (see also antigen-presenting cell).
accessory molecules: Molecules other than the antigen receptor and major histocompatability complex (MHC) that participate in cognitive, activation, and effector functions of T lymphocyte responsiveness.
acquired immune response: See adaptive immune response.
activation-induced cell death: See apoptosis.
acute-phase proteins: A series of proteins, found in the blood shortly after the onset of an infection, that participate in the early phases of host defense against infection.
acute-phase response (APR): An early response stimulated by cytokines which include interleukin-1, interleukin-6, interferons and tumor necrosis factor. As a result, acute phase proteins. These include C-reactive protein, levels of which rise within a few hours of the response. Infection, inflammation, tissue injury, and, very infrequently, neoplasm may be associated with APR.
adaptive immune response: The response of antigen-specific lymphocytes to anti gen including the development of immunologic memory; also known as acquired immune response.
ADCC: See antibody-dependent, cell-mediated cytotoxity.
adenosine deaminase (ADA) deficiency: A form of severe combined immunodeficiency (SCID) in which affected individuals lack an enzyme, adenosine deaminase (ADA), which catalyzes the deamination of adenosine as well as deoxyadenosine to produce inosine and deoxyinosine, respectively.
adhesion molecules: Mediate the binding of one cell to other cells or to extracellular matrix proteins, integrins, selectins, and members of the immunoglobulin gene superfamily. These molecules are important in the operation of the immune system.
adjuvant: A substance, given with antigen, that enhances the response to the injected antigen.
adoptive transfer: The transfer of the capacity to make an immune response by transplantation of immunocompetent cells.
affinity: A measure of the binding constant of a single antigen combining site with a monovalent antigenic determinant.
affinity chromatography: The purification of a substance by means of its affinity for another substance immobilized on a solid support; for example, an antigen can be purified by affinity chromatography on a column of antigen-specific antibody molecules covalently linked to beads.
affinity maturation: The sustained increase in affinity of antibodies for an antigen with time following immunization. The genes encoding the antibody variable regions undergo somatic hypermutation with the selection of B lymphocytes whose receptors express high affinity for the antigen.
agammaglobulinemia: see X-linked agammaglobulinemia.
agglutination: The aggregation of particulate antigen by antibodies. Applies to red blood cells as well as to bacteria and inert particles covered with antigen.
alleles: Variants of a single genetic locus.
alleles: Two or more alternate forms of a gene that occupy the same position or locus on a specific chromosome.
allelic exclusion: The ability of heterozygous lymphoid cells to produce only one allelic form of antigen-specific receptor (Ig or TCR) when they have the genetic endowment to produce both. Genes other than those for the antigen-specific receptors are usually expressed codominantly.
allergen: An antigen responsible for producing allergic reactions by inducing IgE synthesis.
allergic asthma: is constriction of the bronchial tree due to an allergic reaction to inhaled antigen.
allergic rhinitis: is an allergic reaction in the nasal mucosa, also known as hay fever, that causes runny nose, sneezing and tears.
allergy: A term covering immune reactions to nonpathogenic antigens, which lead to inflammation and deleterious effects in the host.
allogeneic: An adjective that describes genetic variations or differences among members or strains of the same species.
allogeneic: Genetically dissimilar within the same species.
allograft: A tissue transplant (graft) between two genetically nonidentical members of a species.
allotypes: Antigenic determinants that are present in allelic (alternate) forms. When used in association with immunoglobulin, allotypes describe allelic variants of im munoglobulins detected by antibodies raised between members of the same species.
alternate complement pathway: The mechanism of complement activation that does not involve activation of the C1-C4-C2 pathway by antigen-antibody complexes, and begins with the activation of C3.
alveolar macrophage: A macrophage found in the lung alveoli that may remove inhaled particulate matter.
anamnestic: Literally, means "does not forget"; it is used to describe immunologic memory, which leads to a rapid increase in response after reexposure to antigen.
anaphylatoxin: Substance capable of releasing histamine from mast cells and basophils.
anaphylaxis: Immediate hypersensitivity response to antigenic challenge, mediated by IgE and mast cells. It is a life-threatening allergic reaction, caused by the release of pharmacologically active agents.
anergy: A state of antigen-specific nonresponsiveness in which a T or B cell is present but functionally unable to respond to antigen.
ankylosing spondylitis: A chronic inflammatory disease affecting the spine, sacroiliac joints, and large peripheral joints. There is a major genetic predisposition, as revealed by increased incidence in selected families. Approximately 90% of patients with ankylosing spondylitis are positive for HLA-B27 as compared with 8% among individuals who are negative for this HLA determinant in the U.S.
antibody: Serum protein formed in response to immunization; antibodies are generally defined in terms of their specific binding to the immunizing antigen.
antibody-dependent, cell-mediated cytotoxicity (ADCC): A phenomenon in which target cells, coated with antibody, are destroyed by specialized killer cells (NK cells and macrophages), which bear receptors for the Fc portion of the coating antibody (Fc receptors). These receptors allow the killer cells to bind to the antibody-coated target.
antigen: Any foreign material that is specifically bound by antibody or lymphocytes; also used loosely to describe materials used for immunization. Compare with immunogen.
antigen presentation: The display of antigen as peptide fragments bound to MHC molecules on the surface of a cell; T cells recognize antigen only when it is presented in this way.
antigen processing: The degradation of proteins into peptides that can bind to MHC molecules for presentation to T cells. All protein antigens must be processed into peptides before they can be presented by MHC molecules.
antigen receptor: The specific antigen-binding receptor on T or B lymphocytes; these receptors are transcribed and translated from rearrangements and translocation of V, D, and J genes.
antigen-binding site: The location on an antibody molecule where an antigenic determinant or epitope combines with it. The antigen-binding site is located in a cleft bordered by the N-terminal variable regions of heavy and light chain parts of the Fab region.
antigen-binding site: The part of an immunoglobulin molecule or T-cell receptor that binds antigen specifically.
antigenic determinant: A single antigenic site or epitope on a complex antigenic molecule or particle.
antigen-presenting cell (APC): A specialized type of cell, bearing cell-surface class II MHC (see major histocompatibility complex) molecules, involved in processing and presentation of antigen to T cells.
anti-immunoglobulin antibodies: Antibodies against immunoglobulin constant domains that are useful for detecting bound antibody molecules in immunoassays and other applications.
antiserum: (plural: antisera)The fluid component of clotted blood from an immune individual that contains a heterogeneous collection of antibodies against the molecule used for immunization. Such antibodies bind the antigen used for immunization. Each has its own structure, its own epitope on the antigen, and its own set of cross- reactions. This heterogeneity makes each antiserum unique.
antiserum (plural: antisera): The fluid component of clotted blood from an immune individual that contains antibodies against the molecule used for immunization. Antisera contain heterogeneous collections of antibodies, which bind the antigen used for immunization. This heterogeneity makes each antiserum unique.
antitoxin: Antibody specific for exotoxins produced by certain microorganisms such as the causative agents of diphtheria and tetanus.
APC: See antigen-presenting cell.
apoptosis: A form of programmed cell death caused by activation of endogenous molecules leading to the fragmentation of DNA.
appendix: A gut-associated lymphoid tissue located at the beginning of the colon.
Arthus reaction: A hypersensitivity reaction produced by local formation of antigen-antibody aggregates that activate the complement cascade and cause thrombosis, hemorrhage, and acute inflammation.
asthma: A disease of the lungs characterized by reversible airway obstruction (in most cases), inflammation of the airway with prominent eosinophil participation, and increased responsiveness by the airway to various stimuli. Some cases of asthma are allergic (see allergic asthma) and are mediated, in part, by IgE antibody to environmental allergens. Other cases are provoked by nonallergic factors.
ataxia telangiectasia: A disorder characterized by cerebellar ataxia, oculocutaneous telangiectasis, variable immunodeficiency which affects the function of both T and B lymphocytes, the development of lymphoid malignancies, and recurrent sinopulmonary infections.
atopy: A term used to describe IgE-mediated allergic responses in humans, usually showing a genetic predisposition.
autochthonous: Pertaining to self.
autograft: A tissue transplant from one area to another on a single individual.
autoimmunity: An immune response to self tissues or components. Such an immune response may have pathologic consequences leading to autoimmune diseases.
autologous: Derived from the same individual, self.
avidity: The summation of multiple affinities, for example, when a polyvalent antibody binds to a polyvalent antigen.
azathioprine: A potent immunosuppresive drug that is converted to its active form in vivo and then kills rapidly proliferating cells, including lymphocytes responding to grafted tissues.
b-pleated sheet: A protein configuration in which the b sheet polypeptide chains are extended and have a 35-nm axial distance. Hydrogen bonding between NH and CO groups of separate polypeptide chains stabilizes the molecules.
B cell: See B lymphocyte.
B lymphocyte (B cell): The precursor of an antibody-forming plasma cell; expresses immunoglobulin on its surface.
B7: A costimulatory homodimeric immunoglobulin superfamily protein whose expression is restricted to the surface of accessory cells (e.g. B cells and macrophages) that interact with T lymphocytes . The ligand for B7 is CD28.
BALT: See bronchus-associated lymphoid tissue.
bare lymphocyte syndrome: Failure to express class I HLA-A, -B, or -C major histocompatibility antigens due to defective b₂ microglobulin expression on the cell surface. In some individuals, the class II HLA-DR molecules are also not expressed.
basophils: White blood cells containing granules that stain with basic dyes. They are thought to have a function similar to mast cells.
BCG (bacille Calmette-Guerin): A Mycobacterium bovis strain that has long been used in Europe as a vaccine against tuberculosis, but has not gained popularity in the U.S.
BCR: B-cell receptors. See B lymphocyte.
Bence-Jones protein: Dimers of immunoglobulin light chains in the urine of patients with multiple myeloma.
blk: see tyrosine kinases.
blocking antibody: A functional term for an antibody molecule capable of blocking the interaction of antigen with other antibodies or with cells.
bone marrow: The site of hematopoiesis, in which stem cells give rise to the cellular elements of blood, including red blood cells, monocytes, polymorphonuclear leukocytes, platelets, and lymphocytes.
bone marrow transplantation: A procedure used to treat both nonneoplastic and neoplastic conditions not amenable to other forms of therapy. It has been especially used in cases of aplastic anemia, acute lymphocytic leukemia, and acute nonlymphocytic leukemia.
bronchus-associated lymphoid tissue (BALT): Secondary lymphoid organs connected to the bronchial tree.
bursa of Fabricius: Site of development of B cells in birds; an outpouching of the cloaca.
C region: See constant region.
C_H50 unit: The amount of complement (serum dilution) that induces lysis of 50% of erythrocytes coated with specific antibody.
C1 deficiencies: Patients with these defects may manifest systemic lupus erythematosus, glomerulonephritis or pyogenic infections as well as an increased incidence of type III (immune complex) hypersensitivity diseases. Only a few cases of C1q, Clr, or Clr and Cls deficiencies have been reported.
C1 esterase inhibitor (C1 INH): A serum protein that inhibits the function of activated C1.
C1q: An 18-polypeptide chain subcomponent of C1, the first component of complement. It commences the classical complement pathway.
C1q deficiency: Deficiency of C1q may be found in association with lupus-like syndromes.
C1r: A subcomponent of C1, the first component of complement in the classical activation pathway. It is a serine esterase.
C1s: A serine esterase that is a subcomponent of C1, the first component of complement in the classical activation pathway. Ca²⁺ binds two C1s molecules to the C1q stalk.
C2: The third complement protein to participate in the classical complement pathway activation. C2 is a single polypeptide chain that unites with C4b molecules on the cell surface in the presence of Mg²⁺.
C2 deficiency: Rare individuals may demonstrate a failure to express C2. Although, in general, no symptoms are associated with this trait, which has an autosomal recessive mode of inheritance, autoimmune-like manifestations that resemble features of certain collagen-vascular diseases, such as systemic lupus erythematosus, may appear.
C3: The fourth complement component to react in the classical pathway, and also a reactant in the alternative complement pathway. C3 contains a and b polypeptide chains linked by disulfide bonds and has an internal thioester bond which permits it to link covalently with surfaces of cells and proteins.
C3 convertase: An enzyme that splits C3 into C3b and C3a. There are two types: one in the classical pathway designated C4b2a and one in the alternative pathway of complement activation termed C3bBb.
C3 tickover: Alternative pathway C3 convertase perpetually generates C3b. C3 internal thioester bond hydrolysis is the initiating event.
C3a: A low molecular weight (9-kD) peptide fragment of complement component C3.
C3b: The principal fragment produced when complement component C3 is split by either classical or alternative pathway convertases, i.e., C4b2a or C3bBb, respectively. It results from C3 convertase digestion of C3's a chain.
C4: A complement component that reacts immediately following C1 in the classical pathway of complement activation.
C5: A complement component comprised of a and b polypeptide chains linked by disulfide bonds that react in the complement cascade following C1, C4b, C2a, and C3b fixation to complexes of antibody and antigen.
C5 convertase: A molecular complex that splits C5 into C5a and C5b in both the classical and the alternative pathway of complement activation.
C5 deficiency: A very uncommon genetic disorder that has an autosomal recessive mode of inheritance. Individuals with this deficiency have a defective ability to form the membrance attack complex (MAC), which is necessary for the efficient lysis of invading microorganisms. They have an increased susceptibility to disseminated infections by Neisseria microorganisms.
C5b: The principal molecular product that remains after C5a has been split off by the action of C5 convertase on C5. It has a binding site for complement component C6 and complexes with it to begin generation of the membrane attack complex (MAC).
C6: A complement component that participates in the membrane attack complex (MAC).
C6 deficiency: A very uncommon genetic defect that has an autosomal recessive mode of inheritance in which affected individuals have only trace amounts of C6 in their plasma. They are defective in the ability to form a membrane attack complex (MAC) and have increased susceptibility to disseminated infections by Neisseria microorganisms.
C7: A complement component that forms a complex with C5b67 is formed when C7 binds to C5b and C6. The complex has the appearance of a stalk with a leaf type of structure.
C7 deficiency: A very uncommon genetic disorder with an autosomal recessive mode of inheritance in which the serum of affected persons contains only trace amounts of C7 in the plasma. They have a defective ability to form a membrane attack complex (MAC) and show an increased incidence of disseminated infections caused by Neisseria microorganisms.
C8: A complement component comprising an a and b chain that participates in the membrane attack complex (MAC).
C8 deficiency: An uncommon genetic disorder with an autosomal recessive mode of inheritance in which affected individuals are missing one or more C8 chains. This is associated with a defective ability to form a membrane attack complex (MAC) and an increased propensity to develop disseminated infections caused by Neisseria microorganisms such as meningococci.
C9: A complement component comprised of a single chain protein that binds to the C5b678 complex on the cell surface. The interaction of 12 to 15 C9 molecules with one C5b678 complex produces the membrane attack complex (MAC).
C9 deficiency: A very uncommon genetic disorder with an autosomal recessive mode of inheritance in which only trace amounts of C9 are present in the plasma of affected persons. There is a defective ability to form the membrane attack complex (MAC).
CAM: Cell-surface adhesion molecule. See adhesion molecules.
carcinoembryonic antigen (CEA): A membrane glycoprotein epitope that is present in the fetal gastrointestinal tract in normal conditions. CEA levels are elevated in almost one third of patients with colorectal, liver, pancreatic, lung, breast, head and neck, cervical, bladder, medullary, thyroid, and prostatic carcinoma.
carrier: A large immunogenic molecule or particle to which a hapten or other non immunogenic, epitope-bearing molecule may attach, allowing it to become immunogenic.
caspases: are a family of closely related cysteine proteases that cleave proteins at aspartic acid residues. They have important roles in apoptosis.
CD: See cluster of differentiation and Appendix.
CDR: See complementarity-determining regions.
CEA: See carcinoembryonic antigen.
cell-mediated cytotoxicity (CMC): Killing (lysis) of a target cell by an effector lymphocyte.
cell-mediated immunity (CMI): Immune reaction mediated by T cells, in contrast to humoral immunity, which is antibody-mediated. Also referred to as delayed- type hypersensitivity.
central lymphoid organs: are sites of lymphocyte development. In humans, B lymphocytes develop in bone marrow. In contrast, lymphocytes develop with the thymus from bone-marrow derived progenitors.
CFU: Abbreviation for colony-forming unit.
Chediak-Higashi syndrome: A childhood disorder with an autosomal recessive mode of inheritance that is identified by the presence of large lysosomal granules in leukocytes that are very stable and undergo slow degranulation.
chemokines: Small cytokines of relatively low molecular weight, released by a variety of cells, and involved in the migration and activation primarily of phagocytic cells and lymphocytes. They have a central role in inflammatory responses.
chemotaxis: Migration of cells along a concentration gradient of an attractant.
chimera: Refers to an individual containing cellular components derived from another genetically distinct individual. In Greek mythology, an animal possessing the head of a lion, the body of a goat, and the tail of a snake.
chronic granulomatous disease (CGD): A disorder that is inherited as an X-linked trait in two thirds of the cases and as an autosomal recessive trait in the remaining one third. The disease is characterized by an enzyme defect associated with NADPH oxidase. This enzyme deficiency causes neutrophils and monocytes to have decreased consumption of oxygen and diminished glucose utilization by the hexose monophosphate shunt.
chronic lymphocytic leukemia (CLL): A B cell leukemia in which long-lived small lymphocytes continually collect in the spleen, lymph nodes, bone marrow, and blood. CLL cells express a monoclonal immunoglobulin on their surface.
class II-associated invariant chain peptide (CLIP): A peptide of variable length cleaved from the invariant chain by proteases. CLIP remains associated with MHC class II molecules in an unstable form until it is removed by the HLA-DM protein.
class switch: See isotype switch.
classical complement pathway: The mechanism of complement activation initiated by antigen-antibody aggregates and proceeding by way of C1 to C9.
clonal anergy: The interaction of a B or T lymphocyte with an antigen leading to its functional inactivation. Anergy can result when the lymphocyte interacts with antigen in the absence of a second signal, usually required for cell activation.
clonal deletion: The loss of lymphocytes of a particular specificity due to contact with either self or foreign antigen.
clonal selection theory: The prevalent concept that specificity and diversity of an immune response are the result of selection by antigen of specifically reactive clones from a large repertoire of preformed lymphocytes, each with individual specificities.
cluster of differentiation (CD): Cluster of antigens with which antibodies react that characterize cell-surface molecules.
cold agglutinin: An antibody that agglutinates particulate antigen, such as bacteria or red cells, optimally at temperatures less than 37º. In clinical medicine, the term usually refers to antibodies against red blood cell antigens which develop in the "cold agglutinin syndrome."
colony-stimulating factors (CSF): Glycoproteins that govern the formation, differentiation and function of hematopoietic progenitor cells (stem cells).
combinatorial joining: The joining of segments of DNA to generate new combinations of Ig or TCR genes during the development of B and T cells. Combinatorial joining allows multiple opportunities for two sets of genes to combine in different ways.
common variable immunodeficiency (CVID): A relatively common congenital or acquired immunodeficiency that may be either familial or sporadic. The familial form may have a variable mode of inheritance. Hypogammaglobulinemia is common to all of these patients and usually affects all classes of immunoglobulin, but in some cases only IgG is affected.
complement: A series of serum proteins involved in the mediation of immune reactions. The complement cascade is triggered classically by the interaction of antibody with specific antigen.
complement receptors (CR): Cell-surface proteins on various cells that recognize and bind complement proteins that have bound pathogens or other antigens. CR on phagocytes allow them to identify pathogens coated with complement proteins for uptake and destruction. Complement receptors include CR1, the receptor for C1q, CR2, CR3, and CR4.
complementarity-determining regions (CDRs): Parts of immunoglobulins and T-cell receptors that determine their specificity and make contact with specific ligand. The CDRs are the most variable part of the molecule and contribute to the diversity of these molecules. There are three such regions (CDR1, CDR2, and CDR3) in each V domain.
complete Freund's adjuvant (CFA): See Freund's complete adjuvant.
concanavalin A (con A): A lectin derived from the jack bean (Canavalia ensiformis) that stimulates T lymphocytes to undergo mitosis and proliferate, and induces erythrocyte agglutination.
conformational epitopes: or discontinuous epitopes, on a protein antigen are formed from several separate regions in the primary sequence of a protein brought together by protein folding. Antibodies that bind conformational epitopes bind only native folded proteins.
conformational epitopes: Discontinuous epitopes on a protein antigen that are formed from several separate regions in the primary sequence of a protein when brought together by protein folding. Antibodies that bind conformational epitopes bind only native-folded proteins.
congenic (also coisogenic): Describes two individuals who differ only in the genes at a particular locus and are identical at all other loci.
constant region (C region): The invariant carboxyl-terminal portion of an immu noglobulin or TCR molecule, as distinct from the variable region at the amino terminus of the chain.
contact dermatitis: A type IV, T lymphocyte-mediated hypersensitivity reaction of the delayed type that develops in response to an allergen applied in the skin.
contact hypersensitivity: A form of delayed-type hypersensitivity (type IV) in which T cells respond to antigens that are introduced by contact with the skin. Poison ivy hypersensitivity is a contact hypersensitivity reaction due to T-cell responses to the chemical antigen pentadecacatechol in poison ivy leaves.
convertase: An enzymatic activity that converts a complement protein into its reactive form by cleaving it. Generation of the C3/C5 convertase is the pivotal event in complement activation.
Coombs test: A test named for its originator, R.R.A. Coombs, used to detect antibodies by addition of an anti-immunoglobulin antibody.
corticosteroids: are steroid hormones (e.g. cortisone) that are lympholytic and are derived from the adrenal cortex. Glucocorticoids such as prednisone or dexamethasone can diminish the size and lymphocyte content of lymph nodes and spleen, while sparing proliferating myeloid or erythroid stem cells of the bone marrow.
costimulatory molecules: Membrane-bound or secreted products of accessory cells that activate signal transduction events in addition to those induced by MHC/TCR interactions. They are required for full activation of T cells.
CR: See complement receptors.
C-reactive protein (CRP): is a serum protein produced by liver cells as part of the acute phase response. It binds to phosphatidylcholine, a component of the surface of many bacteria. As a result of CRP binding to its surface, the bacterium is more easily taken up (opsonized) by phagocytic cells.
cromolyn sodium: A drug that blocks the release of pharmacological mediators from mast cells and diminishes the symptoms and tissue reactions of type I hypersensitivity (i.e., anaphylaxis) mediated by IgE.
cross-reactivity: The ability of an antibody, specific for one antigen, to react with a second antigen; a measure of relatedness between two different antigenic substances.
CTLA-4: The high-affinity receptor for B7 molecules expressed on T cells.
cyclophosphamide: An immunosuppressive drug that is more toxic for B than for T lymphocytes. Consequently, it is a more effective suppressor of humoral antibody synthesis than of cell-mediated immune reactions.
cyclophosphamide: An alkylating agent that is used as an immunosuppressive drug which acts by killing rapidly dividing cells, including lymphocytes proliferating in response to antigen.
cyclosporin A: An immunosuppresive drug that inhibits signaling from the T-cell receptor, preventing T-cell activation and effector function. It binds to cyclophilin, and this complex binds to an inactivates the serine/threonine phosphatase calcineurin.
cytokine receptors: Cellular receptors for cytokines. Binding of the cytokine to the cytokine receptor stimulates signal transduction resulting in new activities in the cell, such as growth, differentiation, or death.
cytokines: Soluble substances secreted by cells, which have a variety of effects on other cells.
cytophilic antibody: An antibody that attaches to a cell surface through its Fc region. It binds to Fc receptors on the cell surface. For example, IgE molecules bind to the surface of mast cells and basophils in this manner.
cytotoxic T cells: T cells that can kill other cells. Most cytotoxic T cells are MHC class 1-restricted CD8⁺ T cells, but CD4⁺ T cells can also kill target cells in some cases.
cytotoxins: are proteins made by cytotoxic T cells that participate in the destruction of target cells. Perforins and granzymes or fragmentins are the major defined cytotoxins.
D gene: A small segment of immunoglobulin heavy-chain or T-cell receptor DNA, coding for the third hypervariable region of the receptors.
decay-accelerating factor (DAF): A membrane glycoprotein of normal human erythrocytes, leukocytes, and platelets, but absent from the red blood cells of paroxysmal nocturnal hemaglobulinuria patients. It facilitates dissociation of classical complement pathway C3 convertase (C4b2a) into C4b and C2a.
degranulation: A mechanism whereby cytoplasmic granules in cells fuse with the cell membrane to discharge the contents from the cell. A classic example is degranulation of the mast cell or basophil in immediate (type I) hypersensitivity.
delayed-type hypersensitivity (DTH): A form of cell-mediated immunity elicited by antigen present in the skin. The reaction is mediated by CD4⁺T_H1 cells and involves release of cytokines and recruitment of monocytes and macrophages. It is called "delayed-type" because the reaction appears hours to days (usually 24-48 hours) after antigen is injected.
dendritic cells: Interdigitating reticular cells, derived from bone-marrow precursors, that are found in T-cell areas of lymphoid tissues. They have a branched or dendritic morphology and are the most potent stimulators of T-cell responses. Dendritic cells present in nonlymphoid tissues do not appear to stimulate T-cell responses until they are activated and migrate to lymphoid tissues.
desensitization: A procedure in which allergic individuals are exposed to increasing doses of allergen with the goal of inhibiting their allergic reactions. The mechanism responsible for this effect probably involves shifting the response from CD4⁺T_H2 to T_H1 cells and thus changing the antibody produced from IgE to IgG.
determinant: Part of the antigen molecule that binds to an antibody-combining site or to a receptor on T cells; also termed epitope (see hapten and epitope).
diapedesis: is the movement of blood cells, particularly leukocytes, from the blood across blood vessel walls into tissues.
differentiation antigen: A cell-surface antigenic determinant found only on cells of a certain lineage and at a particular developmental stage; used as an immunologic marker.
DiGeorge syndrome: is a recessive genetic immunodeficiency disease in which there is a failure to develop thymic epithelium, and is associated with absent parathyroid glands and large vessel anomalies. It seems to be due to a developmental defect in neural crest cells.
diphtheria toxoid: An immunizing preparation generated by formalin inactivation of Corynebacterium diphtheriae exotoxins. This toxoid, which is used in the active immunization of children against diphtheria, is usually administered as a triple vaccine, together with pertussis microorganisms and tetanus toxoid (DPT).
diversity gene segments: see D gene.
domain: A compact segment of an immunoglobulin or TCR chain, made up of amino acids around an S-S bond.
double-negative thymocytes: are immature T cells within the thymus that lack expression of the two co-receptors, CD4 and CD8.
double-positive thymocytes: are an intermediate stage in T-cell development in the thymus and are characterized by expression of both the CD4 and the CD8 co-receptor proteins.
DP, DQ, and DR molecules: Human MHC (HLA) class II molecules of humans found on B cells and antigen-presenting cells.
DTH: See delayed-type hypersensitivity.
ECAM: Endothelial cell adhesion molecule. See adhesion molecules.
effector cells: Lymphocytes that can mediate the removal of pathogens or antigens from the body without the need for further differentiation. Effectors are distinct from naive lymphocytes, which must proliferate and differentiate before they can mediate effector functions. They are also distinct from memory cells which must differentiate and sometimes proliferate before they become effector cells.
ELISA: See enzyme-linked immunosorbent assay.
elispot assay: is an adaptation of ELISA in which cells are placed over antibodies or antigens attached to a plastic surface. The antigen or antibody traps the cells' secreted products, which can then be detected by using an enzyme-coupled antibody that cleaves a colorless substrate to make a localized colored spot.
encapsulated bacteria: have thick carbohydrate coats that protect them from phagocytosis. Encapsulated bacteria can cause extracellular infections and are effectively engulfed and destroyed by phagocytes only if they are first coated with antibody and/or complement produced in an adaptive immune response.
endocytosis: A mechanism whereby substances are taken into a cell from the extracellular fluid by pinching off plasma membrane vesicles.
endogenous pyrogens: Cytokines (e.g. IL-1, TNF-a) that can induce a rise in body temperature. They are distinct form exogenous substances such as endotoxin from gram-negative bacteria that induce fever by triggering endogenous pyrogen synthesis.
endotoxins: Bacterial toxins that are released when bacterial cells are damaged or destroyed. The most important endotoxin is the lipopolysaccharide of gram-negative bacteria, which induces the synthesis inflammatory cytokines.
enzyme-linked immunosorbent assay (ELISA): An assay in which an enzyme is linked to an antibody and a colored substrate is used to measure the activity of bound enzyme and hence the amount of bound antibody.
eosinophils: White blood cells involved in allergic responses and thought to be important in defense against parasitic infections. See hemolytic disease of the newborn.
epitope: An alternative term for antigenic determinant.
erythroblastosis fetalis: A human fetal disease induced by IgG antibodies passed across the placenta from mother to fetus that are specific for fetal red blood cells, leading to their destruction.
erythropoietin: A glycoprotein produced by the kidney, based on the presence of substances such as heme in the kidneys which are oxygen sensitive. It stimulates red blood cell production.
exocytosis: The release of intracellular vesicle content to the exterior of the cell. The vesicles make their way to the plasma membrane, with which they fuse to permit the contents to be released to the external environment.
exon: The region of DNA coding for a protein or a segment of a protein.
experimental allergic encephalomyelitis (EAE): is an experimental inflammatory disease of the central nervous system that develops after animals are immunized with neural antigens together with an adjuvant.
F(ab)' 2: A fragment of an antibody containing two antigen-binding sites; generated by cleavage of the antibody molecule with the enzyme pepsin, which cuts at the hinge region C-terminally to the inter-heavy-chain disulfide bond.
Fab: Fragment of antibody containing one antigen-binding site; generated by cleavage of the antibody with the enzyme papain, which cuts at the hinge region N- terminally to the inter-heavy-chain disulfide bond and generates two Fab fragments from one antibody molecule.
FACS: see fluorescence-activated cell sorter.
factor B: An alternative complement pathway component which combines with C3b and is cleaved by factor D to produce alternative pathway C3 convertase.
factor H: A regulator of complement in the blood that unites with C3b and facilitates dissociation of alternative complement pathway C3 convertase, designated C3bBb, into C3b and Bb.
factor I: A serine protease that splits the a chain of C3b to produce C3bi and the a chain of C4b to yield C4bi.
factor P (properdin): A key participant in the alternative pathway of complement activation that combines with C3b and stabilizes alternative pathway C3 convertase (C3bB) to produce C3bBbP.
Farmer's lung: is a hypersensitivity disease caused by the interaction of IgG antibodies with large amounts of an inhaled allergen in the alveolar wall of the lung, causing alveolar wall inflammation and compromising gas exchange.
Fas: A member of the TNF receptor family that is expressed on certain cells and makes them susceptible to killing by cells expressing Fas ligand. Binding of Fas ligand to Fas triggers apoptosis in the Fas-bearing cells.
Fas ligand (FasL): A cell-surface member of the TNF family of proteins. Binding of Fas ligand to Fas triggers apoptosis in the Fas-expressing cell.
Fc: Fragment of antibody without antigen-binding sites, generated by cleavage with papain; the Fc fragment contains the C-terminal domains of the domains of the immunoglobulin heavy chains.
Fc receptor (FcR): A receptor on a cell surface with specific binding affinity for the Fc portion of an antibody molecule. Fc receptors are found on many types of cells.
Fce receptor (FceR): A mast cell and leukocyte receptor for the Fc region of IgE. When immune complexes bind to Fce receptors, the cell may respond by releasing the mediators of immediate hypersensitivity, such as histamine and serotonin. There are two varieties of Fce receptors, designated FceRI and FceRII (CD23). Fce RI represents a high-affinity receptor found on mast cells and basophils. FceRII represents a low-affinity receptor.
FITC: See fluorescein isothiocyanate.
FK506, or tacrolimus: is an immunosuppressive ploypeptide drug that inactivates T cells by inhibiting signal transduction from the T-cell receptor. FK506 and cyclosporin A are the most commonly used immunosuppressive drugs in organ transplantation.
fluorescein isothiocyanate (FITC): A fluorescent dye (a fluorchrome) which emits a yellow-green color and can be conjugated to antibody or other proteins.
fluorescence microscopy: A microscope method which uses ultraviolet light to illuminate a tissue or cell stained with a fluorochrome-labeled substance such as an antibody against an antigen of interest in the tissue.
fluorescence-activated cell sorter (FACS): An instrument that uses a laser to differentially deflect cells bound to fluorochrome-linked antibodies thus sorting the cells into fluorescent-positive and fluorescent-negative populations.
fluorescent antibody: An antibody coupled with a fluorescent dye, used to detect antigen on cells, tissues, or microorganisms.
follicle: Circular or oval areas of lymphocytes in lymphoid tissues rich in B cells. They are present in the cortex of lymph nodes and in the splenic white pulp. Primary follicles contain B lymphocytes that are small and medium sized. Antigen stimulation causes development of secondary follicles which contain large B lymphocytes in the germinal centers in which tingible body macrophages (those phagocytizing nuclear particles) and follicular dendritic cells are also present.
follicular dendritic cells: Cells within lymphoid follicles which are crucial in selecting antigen-binding B cells during antibody responses. Their origin is uncertain. They have Fc receptors that are not internalized by receptor-mediated endocytosis and thus hold antigen-antibody complexes on their surface for long periods.
Freund's complete adjuvant: An oil containing killed mycobacteria and an emulsifier, which, when emulsified with an immunogen in aqueous solution, enhances the immune response to that immunogen after injection. Termed incomplete Freund's adjuvant if mycobacteria are not included.
Fyn: see tyrosine kinase.
G proteins: are proteins that bind GTP and convert it to GDP in the process of cell signal transduction.
GALT: See gut-associated lymphoid tissue.
gene knockout: Jargon for gene disruption by homologous recombination.
genetic immunization: is a novel technique for inducing adaptive immune responses in which a plasmid DNA encoding a protein of interest is injected, usually into muscle; the protein is then expressed in vivo and elicits antibody and T-cell responses to the protein encoded by the DNA.
genotype: All the genes possessed by an individual; in practice it refers to the particular alleles present at the loci in question.
germ line: Refers to genes in germ cells as opposed to somatic cells. In immunology, it refers to genes in their unrearranged state rather than those rearranged for production of immunoglobulin or TCR molecules.
germinal centers: Secondary lymphoid structures that are sites of intense B-cell proliferation, selection, maturation, and death during antibody responses. They form around follicular dendritic cell networks after migration of B cells into lymphoid follicles.
glomerulonephritis: A group of diseases characterized by glomerular injury. Immune mechanisms are responsible for most cases of primary glomerulonephritis and many of the secondary glomerulonephritis group. Over 70% of glomerulonephritis patients have glomererular deposits of immunoglobulins, frequently with complement components.
Goodpasture's syndrome: An autoimmune disease in which autoantibodies against basement membrane or type IV collagen are produced and cause extensive vasculitis. It is rapidly fatal.
graft-versus-host reaction (GVH): The pathologic consequences of a response generally initiated by transplanted immunocompetent T lymphocytes into an allogeneic, immunologically incompetent host. The host is unable to reject the grafted T cells and becomes their target.
Granulocyte: see polymorphonuclear leukocyte.
granulocyte-macrophage colony-stimulating factor (GM-CSF): A cytokine involved in the growth and differentiation of myeloid and monocytic lineage cells, including dendritic cells, monocytes and tissue macrophages, and cells of the granulocyte lineage.
granuloma: An organized structure in the form of a mass of mononuclear cells at the site of a persisting inflammation; the cells are mostly macrophages with some T lymphocytes at the periphery. It is a typical delayed hypersensitivity reaction that is persistent due to the continuous presence of a foreign body or infection.
Graves' disease: An autoimmune disease in which antibodies against the thyroid-stimulating hormone receptor cause overproduction of thyroid hormone and thus hyperthyroidism.
Guillain-Barre syndrome: A type of idiopathic polyneuritis in which autoimmunity to peripheral nerve myelin leads to a condition characterized by chronic demyelination of the spinal cord and peripheral nerves.
gut-associated lymphoid tissue (GALT): Lymphoid tissue situated in the gastrointestinal mucosa and submucosa which constitutes the gastrointestinal immune sys tem. GALT is present in the Peyer's patches, appendix, and tonsils.
GVH: See graft versus host reaction.
H chain: See heavy chain.
H-2: The major histocompatibility complex of the mouse. Haplotypes are designated by a lower-case superscript, as in ^H-2b.
H-2 complex: The major histocompatibility complex situated on chromosome 17 of the mouse; contains subregions K, I, D, and L.
haplotype: A linked set of genes associated with one haploid genome. The term is used mainly in connection with the linked genes of the major histocompatibility complex (MHC), which are usually inherited as one haplotype from each parent. Some MHC haplotypes are over-represented in the population, a phenomenon known as linkage disequilibrium.
haplotype: A particular combination of closely linked genes on a chromosome in herited from one parent.
hapten: A compound, usually of low molecular weight, that is not itself immuno genic but that, after conjugation to a carrier protein or cells, becomes immunogenic and induces antibody, which can bind the hapten alone in the absence of carrier.
Hashimoto's thyroiditis: An autoimmune disease characterized by persistent high levels of antibody against thyroid-specific antigens. These antibodies recruit NK cells to the tissue, leading to damage and inflammation.
HAT: Hypoxanthine-aminopterin-thymidine.
heavy chain (H chain): The larger of the two types of chains that comprise a normal immunoglobulin or antibody molecule.
helper T cells: A class of T cells that helps trigger B cells to make antibody against thymus-dependent antigens. Helper T cells also help in the differentiation of other T cells such as cytotoxic T cells.
hemagglutinin: Any substance that causes red blood cells to agglutinate. The hemagglutinins in human blood are antibodies that recognize the ABO blood group antigens. Influenza and some other viruses have hemagglutinin molecules that bind to glycoproteins on host cells to initiate the infectious process.
hematopoiesis: The generation of the cellular elements of blood, including the red blood cells, leukocytes, and platelets.
hematopoietic stem cell: A bone marrow cell that is undifferentiated and serves as a precursor for multiple cell lineages. These cells are also demonstrable in the yolk sac and later in the liver of the fetus.
hemolytic disease of the newborn: or erythroblastosis fetalis, is caused by a maternal IgG antibody response to paternal antigens expressed on fetal red blood cells. The usual target of this response is the Rh blood group antigen. The maternal anti-Rh IgG antibodies cross the placenta, and bind to and lead to the lysis of fetal red blood cells.
herd immunity: The protection of unimmunized members of a community by the resistance of the majority of the population to a particular pathogen; generally conferred by vaccinating most of the susceptible individuals.
hereditary angioedema: A disorder in which recurrent attacks of edema occur in the skin and gastrointestinal and respiratory tracts. It is due to decreased or absent C1 inhibitor (C1 INH). The most serious consequence of this disorder is epiglottal swelling leading to suffocation.
heterodimer: A molecule comprised of two components that are different, but closely joined structures, such as a protein comprised of two separate chains. Examples include the T cell receptor conprised of either a and b chains or of g and d chains, and class I as well as class II histocompatibility molecules.
heterophile antigen: A cross-reacting antigen that appears in widely ranging species such as humans and bacteria.
heterozygous: heterozygous Individuals for a particular gene have two different alleles of that gene.
HEV: See high endothelial venules.
high endothelial venules (HEV): Specialized venules found in lymphoid tissues. Lymphocytes migrate from blood into lymphoid tissues by attaching to and migrating across the high endothelial cells of these vessels.
hinge region: A flexible, open segment of an antibody molecule that allows bending of the molecule. The hinge region is located between Fab and Fc and is susceptible to enzymatic cleavage.
histamine: A vasoactive amine stored in mast cell granules which is released by antigen binding to IgE molecules on mast cells, causing dilation of local blood vessels and smooth muscle contraction. Histamine release produces some of the symptoms of immediate hypersensitivity reactions.
histocompatibility: Literally, the ability of tissues to be compatible; in immunology, it means identity in all transplantation antigens. These antigens, in turn, are collectively referred to as histocompatibility antigens.
HIV: See human immunodeficiency virus.
HLA: See human leukocyte antigen.
Hodgkins's disease: is a malignant disease in which antigen-presenting cells that resemble dendritic cells seem to be the transformed cell type. Hodgkin's lymphoma is a form of Hodgkin's disease in which lymphocytes predominate, and it has a much better prognosis than the nodular sclerosis form of this disease in which the predominant cell type is non-lymphoid.
homodimer: A protein comprised of dual peptide chains that are identical.
human immunodeficiency virus (HIV): Retrovirus that infects human CD4⁺ cells and causes AIDS.
Human Leukocyte Antigen (HLA): The human major histocompatibility complex; contains the genes coding for the polymorphic MHC class I and II class molecules and many other important genes.
humanization: A term used to describe the genetic engineering of mouse hypervariable loops of a desired specificity into otherwise human antibodies. The DNA encoding hypervariable loops of mouse monoclonal antibodies or V regions selected in phage display libraries is inserted into the framework regions of human immunoglobulin genes. This allows the production of antibodies of a desired specificity that do not cause an immune response in humans treated with them.
humanization: Refers to the genetic engineering by which mouse V(D)J region genes defining a particular antigenic specificity are combined with human genes coding for the rest of the Ig molecule. Results in an antibody with a mouse-defined antigenic specificity but with human effector characteristics. Humanization reduces the immunogenicity of a mouse Ig in humans, making it more effective as an in vivo treatment than a completely mouse molecule.
humoral immunity: refers to immune responses that involve antibody (contrast with cell-mediated immunity: T-cell responses in the absence of antibody). Can be transferred to another individual using antibody-containing serum.
hybridoma: An immortalized hybrid cell resulting from the in vitro fusion of an antibody-secreting B cell with a myeloma; it secretes antibody without stimulation and proliferates continuously, both in vivo and in vitro. The term is also used for a hybrid T cell resulting from the fusion of a T lymphocyte with a thymoma (a malignant T cell); the T-cell hybridoma proliferates continuously and secretes cytokines upon activation by antigen and APC.
hyperacute graft rejection: of an allogenic tissue graft is an immediate reaction caused by natural preformed antibodies that react against antigens on the graft. The antibodies bind to endothelium and trigger the blood clotting cascade, leading to an engorged, ischemic graft and rapid loss of the organ.
hyperacute graft rejection: Rapid (minutes to hours) rejection of a graft mediated by preformed antibodies of the host reacting with the graft.
hypergammaglobulinemia: Elevated serum immunoglobulin levels. A polyclonal increase in immunoglobulins in the serum occurs in any condition where there is continuous stimulation of the immune system, such as chronic infection, autoimmune disease, systemic lupus erythematosus, etc. Hypergammaglobulinemia may also result from a monoclonal increase in immunoglobulin production, as in multiple myeloma, Waldenstrom's macroglobulinemia, or other conditions associated with the formation of monoclonal immunoglobulins.
hyperimmune: A descriptor for an animal with a high level of immunity that is induced by repeated immunization to generate large amounts of functionally effective antibodies, in comparison to animals subjected to routine immunization protocols, perhaps with fewer boosters.
hypersensitivity: State of reactivity to antigen that is greater than normal; denotes a deleterious rather than a protective outcome. Type I: IgE-mediated; type II: antibody specific for a cellular antigen triggers the complement cascade; type III: antigen-antibody complexes deposit in tissues and activate complement; type IV: T-cell-mediated.
hypervariable regions: Portions of the Ig or TCR chains that are highly variable in amino acid sequence from one molecule to another, and that together constitute the binding site for antigen. (see complementarity-determining region).
Ia (I region-associated): An older term for mouse MHC class II genes and molecules; comprise I-A and I-E.
IDC: See interdigitating dendritic cells.
idiotype: The combined antigenic determinants (idiotopes) expressed in the variable region of antibodies of an individual that are directed at a particular antigen.
Ig: See immunoglobulin.
IL: See interleukins.
immature B cell: IgM IgD^- cell in the B cell lineage; easily tolerized by exposure to antigen.
immediate-type hypersensitivity: (Type I) hypersensitivity reaction occurring within minutes after the interaction of antigen and IgE antibody.
immune adherence: The adherence of particulate antigen coated with C3b to cells expressing C3b receptors; results in enhanced phagocytosis of bacteria by macrophages.
immune complex: Molecules formed by the interaction of a soluble (that is, non-particulate) antigen with antibody molecules. Large immune complexes are cleared rapidly, but smaller complexes formed in antigen excess may deposit in tissues resulting in tissue damage.
immune modulators: Substances that control the level of the immune response.
immunity: The general term for resistance to a pathogen.
immunodeficiency: Decrease in immune response that results from absence or defect of some component of the immune system.
immunodiffusion: Identifies antigen or antibody by the formation of antigen-antibody complexes in a gel.
immunogen: A substance capable of inducing an immune response (as well as reacting with the products of an immune response). Compare with antigen.
immunoglobulin (Ig): A general term for all antibody molecules: IgM, IgD, IgG, IgA, IgE; each Ig unit is made up of two heavy chains and two light chains and has two antigen-binding sites.
immunoglobulin superfamily: Proteins involved in cellular recognition and interaction that are structurally and genetically related to immunoglobulins.
immunoreceptor tyrosine-based activation motif (ITAM): A pattern of amino acids in the cytoplasmic tail of many transmembrane receptor molecules, including Iga and Igb and CD3 chains, which are phosphorylated and then associate with intracellular molecules as an early consequence of cell activation.
immunoreceptor tyrosine-based inhibitory motif (ITIM): A pattern of amino acids in the cytoplasmic tail of transmembrane molecules, such as CD32, which negatively regulates cell activation. The ITIM bonds a phosphatase which removes phosphate groups from tyrosine residues in the ITAMs of other membrane molecules.
inflammation: An acute or chronic response to tissue injury or infection involving accumulation of leukocytes, plasma proteins, and fluid.
innate immunity: The antigen-nonspecific mechanisms involved in the early phase of resistance to a pathogen, which include phagocytic cells, cytokines, and complement; not expanded by repeat stimulation with the pathogen.
integrins: A family of two-chain cell-surface adhesion molecules found on leukocytes; important in the adhesion of APC and lymphocytes, and in leukocyte migration into tissues.
intercellular adhesion molecules (ICAMs) 1, 2, and 3: Adhesion molecules on the surface of several cell types, including antigen-presenting cells and T cells that interact with integrins; members of the immunoglobulin superfamily. [fp
interdigitating dendritic cells (IDC): Thymic bone marrow-derived cells which play a critical role in negative selection of developing thymocytes.
interferons (IFN): A group of proteins having antiviral activity and capable of enhancing and modifying the immune response.
interleukins (IL): Glycoproteins secreted by a variety of leukocytes that have effects on other leukocytes.
intron: A segment of DNA that does not code for protein: the intervening sequence of nucleotides between coding sequences or exons.
isoelectric focusing: Protein identification technique; proteins migrate in an electric field under a pH gradient to the pH at which their net charge is zero (their isoelectric point).
isograft: Tissue transplanted between two genetically identical individuals (same as syngraft).
isohemagglutinins: Naturally occurring IgM antibodies specific for the red blood cell antigens of the ABO blood groups; thought to result from immunization by bacteria in the gastrointestinal and respiratory tracts.
isotype switch: The switch which occurs when a B cell stops secreting antibody of one isotype or class and starts producing antibody of a different isotype but with same antigenic specificity; involves joining rearranged VDJ gene unit to a different heavy-chain constant region gene.
isotypes: Also known as antibody classes. Antibodies that differ in the heavy chain constant regions: IgM, IgG, IgD, IgA and IgE. These differences result in distinct biological activities of the antibodies; distinguishable also on the basis of reaction with antisera raised in another species.
ITAM: See immunoreceptor tyrosine-based activation motif.
ITIM: See immunoreceptor tyrosine-based inhibition motif.
J chain (joining chain): A polypeptide involved in the polymerization of IgM and IgA.
J gene: A gene segment coding for the J or joining segment in immunoglobulin or T-cell receptor chains; in Ig light chains and TCR a and g, a V gene segment rearranges to a J segment; in Ig heavy chains and TCR b and d, a D gene segment rearranges to a J segment.
JAK: See Janus kinases.
Janus kinases (JAK): Tyrosine kinases activated by cytokines binding to their cellular receptors.
killer inhibitory receptor (KIR): a receptor expressed on NK cells that binds to MHC class I molecules on target cells; ligation of MHC class I inhibits the signaling that would otherwise lead to target cell killing.
killer T cell: A T cell that kills a target cell expressing foreign antigen bound to MHC molecules on the surface of the target cell. Also called cytotoxic T cell.
KIR: See killer inhibitory receptor.
L chain: See light chain.
LAK cells: See lymphokine-activated killer cells.
Langerhans cell: Cell of the monocyte/dendritic cell family that takes up and processes antigens in the epidermal layer of the skin; migrates through lymphatics to lymph nodes draining the site of exposure to antigen, where it differentiates into a dendritic cell.
leukemia: Uncontrolled proliferation of a malignant leukocyte.
leukocytes: White blood cells; comprise monocytes/macrophages, lymphocytes and polymorphonuclear cells.
leukocyte common antigen (LCA, CD45): An antigen shared in common by both T and B lymphocytes.
ligand: A molecule or part of a molecule that binds to a receptor.
ligation: The binding of a molecule or a part of a molecule to a receptor.
light chain (L chain): The light chain of the immunoglobulin molecule; occurs in two forms: k or l.
linked recognition: The requirement for the T helper and B cell involved in the antibody response to a thymus-dependent antigen to interact with different epitopes physically linked in the same antigen.
lipopolysaccharide (LPS): Components of gram-negative bacteria cell walls; also known as endotoxin.
LPS: See lipopolysaccharide.
lymph: Extracellular fluid that bathes tissues; contains tissue products, antigens, antibodies and cells (predominantly lymphocytes).
lymph nodes: Secondary lymphoid organs, in which mature B and T lymphocytes respond to free antigen, or antigen associated with APC, brought in via lymphatic vessels.
lymphatic system: System of vessels through which lymph travels, and which includes organized structures—lymph nodes—at the intersection of vessels. Three major functions: to concentrate antigen from all parts of the body into a few lymphoid organs; to circulate lymphocytes through lymphoid organs so that antigen can interact with rare antigen-specific cells; and to carry products of the immune response (antibody and effector cells) to the bloodstream and tissues.
lymphocytes: Express antigen-specific receptors. Small leukocyte with virtually no cytoplasm, found in blood, tissues, and lymphoid organs such as lymph nodes, spleen, and Peyer's patches. Responsible for specificity, diversity, memory, and self-nonself discrimination.
lymphokine: A cytokine secreted by lymphocytes.
lymphokine-activated killer (LAK) cells: The heterogeneous population of lym phocytes, including NK cells, derived from the in vitro cytokine-driven activation of peripheral blood lymphocytes from a tumor-bearing patient.
lymphoma: Lymphocyte tumors in lymphoid or other tissues; not generally found in the blood.
macrophages: Large phagocytic leukocytes found in tissues; derived from blood monocytes.
major histocompatibility complex (MHC): A cluster of genes encoding polymorphic cell-surface molecules (MHC class I and class II) that are involved in antigen presentation to T cells. These molecules also play a major role in transplantation rejection. Several other nonpolymorphic proteins are encoded in this region.
MALT: See mucosal-associated lymphoid tissue.
mast cell: Bone-marrow derived granule-containing cell found in connective tissues; releases mediators such as histamine and cytokines following cell activation; plays a major role in allergic responses.
mature B cell: B cells with IgM and IgD on their surface.
membrane attack complex: Terminal components of the complement cascade (C7-C9) which form a pore on the surface of a target cell, resulting in cell damage or death.
memory: In the immune system denotes that a second interaction with antigen leads to a more effective and more rapid response than the first interaction (primary response).
MHC: See major histocompatibility complex.
MHC class I molecule: A molecule encoded by genes of the MHC that participates in antigen presentation to CD8⁺ (cytotoxic) T cells.
MHC class III molecules: Proteins including complement components C2, C4, and factor B encoded by genes in the major histocompatibility complex (MHC). Although adjacent to MC class I and class II genes that code for molecules critical in cellular interactions in the immune response, molecules coded for by MHC class III genes are not involved in celluar interactions.
MHC class II molecule: A molecule encoded by genes of the MHC that participates in antigen presentation to CD4⁺ T cells.
MHC restriction: The property of T lymphocytes to respond only when they are presented with the appropriate antigen in association with either self MHC class I or class II molecules.
minor histocompatibility antigens: Antigens encoded outside the MHC which stimulate graft rejection, but not as rapidly as MHC molecules.
mitogen: A substance that stimulates the proliferation of many different clones of lymphocytes.
mixed lymphocyte reaction (MLR): Proliferative response occurring when leuko cytes from two individuals are mixed in vitro; T cells from one individual (the responder) are activated by MHC antigens expressed by APC of the other individual (the stimulator).
MLR: See mixed lymphocyte reaction.
molecular mimicry: Identity or similarity of epitopes expressed by a pathogen and by a self molecule; may explain how autoimmune responses develop.
monoclonal: Means derived from a single clone, the progeny of a single cell. Generally refers to a population of T cells, B cells, or antibody that is homogeneous, and reactive with the same specificity toward an epitope.
monocyte: Phagocytic leukocyte found in the blood; precursor to tissue macrophage.
motif: A pattern of amino acids in the sequence of a molecule critical for the binding of a ligand.
mucosal-associated lymphoid tissue (MALT): System that connects lymphoid structures found in the gastrointestinal and respiratory tracts; includes tonsils, appendix, and Peyer's patches of the small intestine.
multiple sclerosis: Disease of the central nervous system believed to be autoimmune in nature, in which an inflammatory response results in demyelination and loss of neurologic function.
myasthenia gravis: Autoimmune disease in which antibody specific for the acetyl choline receptor expressed in muscle blocks function at the neuromuscular junction.
myeloma: A tumor of plasma cells, generally secreting a single monoclonal immunoglobulin.
natural killer (NK) cells: Large granular lymphocyte-like cells that kill various tumor cells in vitro and may play a role in resistance to tumors; also participate in ADCC; derived from the lymphoid progenitor but distinct from T and B lymphocytes. They do not exhibit antigenic specificity, and their number does not increase by immunization.
negative selection: Step in development of B and T cells at which cells with potential reactivity to self molecules are functionally inactivated.
neutralization: The ability of an antibody to block or inhibit the effects of a virus.
NK cells: See natural killer cells.
opsonization: The coating of a particle such as a bacterium with antibody and/or a complement component (an opsonin) that leads to enhanced phagocytosis by phagocytic cells.
paracortical area (or paracortex): The T-cell area of the lymph node.
passive cutaneous anaphylaxis (PCA): The passive transfer of anaphylactic sensitivity by intradermal injection of serum from a sensitive donor.
passive hemagglutination: Technique for measuring antibody, in which antigen-coated red blood cells are agglutinated by adding antibody specific for the antigen.
passive immunization: Immunization of an individual by the transfer of antibody synthesized in another individual.
pathogen: An agent which causes disease.
PCA: See passive cutaneous anaphylaxis.
PCR: See polymerase chain reaction.
perforin: A molecule synthesized by cytotoxic T cells and NK cells that polymerizes on the surface of a target cell and creates a pore in the membrane, resulting in target cell death.
peripheral lymphoid organs: Lymphoid organs other than the thymus; include spleen, lymph nodes, and mucosal associated lymphoid tissue.
peripheral tolerance: Tolerance induced in mature lymphocytes outside the thymus.
Peyer's patches: Clusters of lymphocytes distributed in the lining of the small intestine.
PHA: See phytohemagglutinin.
phagocytosis: The engulfment of a particle or a microorganism by leukocytes such as macrophages and neutrophils.
phenotype: The physical expression of an individual's genotype.
phosphatase: Enzyme that removes phosphate groups from proteins.
phospholipase C gamma (PLC-g): Enzyme involved in T-cell and B-cell activation pathways; splits phosphatidylinositol bisphosphate (PIP₂) into diacylglycerol (DAG) and inositol triphosphate (IP₃) leading to the activation of two major signaling pathways.
phytohemagglutinin (PHA): A mitogen that polyclonally activates T cells.
pinocytosis: Ingestion of liquid or very small particles by vesicle formation in a cell.
plasma: Fluid component of unclotted blood.
plasma cell: The antibody-producing end-stage of B-cell differentiation.
platelets: Bone-marrow derived cells crucial in blood clotting.
PMN leukocytes: See polymorphonuclear leukocytes.
pokeweed mitogen: A mitogen that polyclonally activates B cells.
polyclonal activator: A substance that induces activation of many clones of either T or B cells. See mitogen.
poly-Ig receptor: Binds to IgA at one surface of an epithelial cell, transports it through the cell, and releases it at the opposite lumenal surface; the IgA can then participate in protecting the mucosal system.
polymerase chain reaction (PCR): Produces large amounts of DNA from a sequence by repeated cycles of synthesis.
polymorphism: Literally, having many shapes; in genetics, the existence of multiple alleles at a particular genetic locus resulting in variants of the gene and product among different members of the species.
polymorphonuclear leukocytes (PMN): Leukocytes containing cytoplasmic granules with characteristic multilobed nucleus; three major types: neutrophils, eosinophils, and basophils.
positive selection: The process by which developing B and T cells receive signals in the primary lymphoid organ in which they are developing to continue their differentiation; in the absence of these signals the cells die.
pre-B cell: Cell in the B cell lineage which has rearranged heavy but not light chain genes; expresses surrogate light chains and m heavy chain at its surface in conjunc tion with Iga and Igb; all these molecules comprise the pre-B cell receptor (pre-BCR).
precipitin reaction: The mixing of soluble antigen and antibody at different proportions that can result in the precipitation of insoluble antigen-antibody complexes.
pre-T cell: Cell in T-lymphocyte differentiation in the thymus that has rearranged TCR b genes and expresses TCR b polypeptide on the surface with the molecule pTa (gp33), forming the pre-T-cell receptor.
primary follicle: Region of a secondary lymphoid organ containing predominantly unstimulated B lymphocytes; develops into a germinal center following antigen stimulation.
primary lymphoid organs: Organs in which the early stages of T- and B-lymphocyte differentiation take place and antigen-specific receptors are first expressed.
primary response: The immune response resulting from first encounter with antigen; generally small, with a long induction phase or lag period, and generates immunologic memory. In the primary B-cell response, mainly IgM antibodies are made.
priming: The activation of naive lymphocytes by exposure to antigen.
pro-B cell: Earliest stage of B cell differentiation in which a heavy chain D-gene segment rearranges to a J-gene segment.
programmed cell death: See apoptosis.
properdin (factor P): A positive regulator of the alternative pathway of complement activation; stabilizes C3bBb.
prophylaxis: Protection.
proteasome: Multiprotein cytoplasmic complex, which catabolizes proteins to 8-9 amino acid peptides.
protein kinase C: Enzyme activated by calcium and diacylglycerol during T- and B-lymphocyte activation.
protooncogenes: Cellular genes regulating growth control; mutation or aberrant expression can lead to malignant transformation of the cell.
provirus: DNA form of a retrovirus integrated into the host DNA.
pseudogene: Sequence of DNA resembling a gene but containing codons that prevent transcription into full-length RNA species.
pyogenic: Refers to the generation of pus at the sites of response to bacteria with large capsules.
pyrogen: A substance that causes fever.
radioallergosorbent test (RAST): A solid-phase radioimmunoassay for detecting IgE antibody specific for a particular allergen.
radioimmunoassay (RIA): A technique for measuring the level of a biologic substance in a sample, by measuring the binding of antigen to radioactively labeled antibody (or vice versa).
RAG-1 and RAG-2 (recombination activating genes): Genes and their products which are critically involved in V(D)J recombination in B and T cells.
rapamycin: An immunosuppressive agent used to prevent transplantation rejection; blocks cytokine production.
receptor: Generally a transmembrane molecule that binds to a ligand on the exterior surface of the cell, leading to biochemical changes inside the cell.
receptor editing: Process by which the rearranged genes of a cell in the B-cell lineage may undergo a secondary rearrangement, generating a different antigenic specificity.
recombination: See V(D)J recombination.
recombination activating genes: See RAG-1 and RAG-2.
repertoire: The complete library of antigenic specificities generated by either B or T lymphocytes to respond to foreign antigen.
RES: See reticuloendothelial system.
reticuloendothelial system (RES): A general term for the network of phagocytic cells.
reverse transcriptase: Enzyme which transcribes the RNA genome of a retrovirus into DNA; used in molecular biology to convert RNA into complementary DNA (cDNA).
rheumatoid arthritis: Autoimmune, inflammatory disease of the joints.
rheumatoid factor: An autoantibody (usually IgM) that reacts with the individual's own IgG; present in rheumatoid arthritis.
SCID: See severe combined immune deficiency disease.
second set rejection: Accelerated rejection of an allograft in a primed recipient.
secondary lymphoid organs: Organs in which antigen-driven proliferation and differentiation of mature B and T lymphocytes take place following antigen recognition.
secretory component: Cleaved component of the poly-Ig receptor that attaches to dimeric IgA and protects it from proteolytic cleavage as it is transported through an epithelial cell.
selectins: A family of cell-surface adhesion molecules found on leukocytes and endothelial cells; bind to sugars on glycoproteins.
sensitization: Prior immunization by antigen; generally used for first encounter with allergen.
sepsis: Infection of the bloodstream.
serology: Use of antibodies to detect antigens.
serum: Residual fluid derived from clotted blood; contains antibodies.
serum sickness: A type III hypersensitivity reaction resulting from deposition of circulating, soluble, antigen-antibody complexes leading to complement and neutrophil activation in tissues such as the kidney; typically induced following therapy with large doses of antibody from a foreign source, such as monoclonal antibodies made in mice (originally, by treating patients with horse serum).
severe combined immune deficiency (SCID): Disease resulting from early block in differentiation pathways of both B and T lymphocytes.
signal transducers and activators of transcription (STATs): Intracellular proteins phosphorylated by Janus kinases as a consequence of cytokine-cytokine receptor engagement.
signal transduction: Processes involved in transmitting the signal received on the outer surface of the cell (e.g., by antigen binding to its receptor) into the nucleus of the cell, which lead to altered gene expression.
SLE: See systemic lupus erythematosus.
slow-reacting substance of anaphylaxis (SRS-A): A group of leukotrienes released by mast cells during anaphylaxis that induces a prolonged contraction of smooth muscle.
somatic gene conversion: nonreciprocal exchange of sequences between genes: part of the donor gene or genes is "copied" into an acceptor gene, but only the acceptor gene is altered; mechanism for generating diverse Ig repertoire in many nonhuman species.
somatic hypermutation: Change in the variable region sequence of an antibody produced by a B cell following antigenic stimulation, resulting in increased antibody affinity for antigen.
spleen: Largest of the secondary lymphoid organs; traps and concentrates foreign substances carried in the blood; composed of white pulp, rich in lymphoid cells, and red pulp, which contains many erythrocytes and macrophages.
STATs: See signal transducers and activators of transcription.
strain: Set of animals (particularly mice and rats) in which every animal is bred to be genetically identical.
superantigen: A molecule that activates all T cells with a particular Vb gene seg ment, irrespective of their Va expression.
suppression: A mechanism for producing a specific state of immunologic unrespon siveness by which one cell or its products inhibits the function of another.
surrogate light chains: Nonrearranging chains (Vl5 and V preB) expressed in con junction with m chain in the pre-B cell; form part of the pre-BCR.
switch region: Region of B cell heavy chain DNA at which recombination occurs in an antigen-stimulated cell; allows isotype switch (e.g., IgM to IgE).
syngeneic: Literally, genetically identical; e.g., monozygotic twins or mice of the same strain.
syngraft: Same as isograft.
systemic lupus erythematosus (SLE): An autoimmune disease which affects many organs of the body, and causes fever and joint pain. Patients produce high levels of antibodies against the components of cell nuclei, particularly DNA, and form circulating soluble antigen-antibody complexes. These complexes deposit in tissues such as the kidney, activate the complement cascade, and result in tissue damage.
T cells: The set of lymphocytes whose differentiation requires the thymus.
T_H1: A subset of CD4⁺ T cells that synthesizes the cytokines IL-2, IFN-g, and TNF- b; these cytokines activate NK cells, macrophages, and CD8⁺ T-cells.
T_H2: A subset of CD4⁺ T cells which synthesizes the cytokines IL-4, IL-5, IL-10, and IL-13; these cytokines predominate in the response to allergens and parasites (B-cell class switching to IgE, and eosinophil activation).
TAP-1 and TAP-2: Molecules that selectively transport peptides from the cytoplasm to the endoplasmic reticulum of cells for binding to MHC class I molecules.
target: A cell killed by one of the body's killer cells, such as a CTL or NK cell.
Tc: T cytotoxic cell.
T-cell receptor (TCR): A two-chain structure on T cells that binds antigen: ab on the major set of T cells, gd on the minor set of T cells. The TCR complex comprises the antigen-binding chains associated at the cell surface with the signal transduction molecules CD3 plus z or h.
TCR: See T-cell receptor.
T-dependent antigen: An immunogen that requires T helper cells to interact with B cells in order to induce antibody synthesis.
terminal deoxynucleotidyl transferase (TdT): Enzyme that inserts nontemplated nucleotides at the junctions of V, D, and J gene segments of Ig and TCR locus DNA; these N-nucleotides increase the diversity of antigen-specific receptors.
thymocytes: T cells differentiating in the thymus.
thymus: The primary lymphoid organ for T-cell differentiation, comprising an outer cortex and inner medulla; developing thymocytes interact with epithelial cells and bone marrow derived macrophages and interdigitating dendritic cells in the thymus.
TIL: See tumor infiltrating lymphocyte.
T-independent antigen: An immunogen that induces antibody synthesis in the absence of T cells or their products; antibodies synthesized generally only of the IgM isotype, and no memory response.
titer: Used generally as an empirical measure of the avidity of an antibody; it is the reciprocal of the last dilution of a titration giving a measurable effect; e.g., if the last dilution of an antibody giving significant agglutination is 1:128, the titer is 128.
TNF: See tumor necrosis factor.
tolerance: Antigen-specific unresponsiveness of B or T cells.
toxic shock syndrome: The systemic reaction produced by the toxin derived from the bacterium [cf2]Staphylococcus aureus ; the toxin acts as a superantigen, which activates a high proportion of CD4⁺ T cells to produce cytokines.
toxoid: A nontoxic derivative of a toxin used as an immunogen for the induction of antibodies capable of cross-reacting with the toxin.
transplantation: Grafting solid tissue (such as a kidney or heart) or cells (particularly bone marrow) from one individual to another. See allograft and xenograft.
tuberculin test: Antigens derived the organism causing tuberculosis are injected subcutaneously; individuals who have been exposed to the organism and those who have been previously vaccinated with BCG develop a delayed hypersensitivity re sponse at the injection site 24—48 hours later.
tumor infiltrating lymphocyte (TIL): Mononuclear cells derived from the inflam matory infiltrate of solid tumors.
tumor necrosis factor (TNF): A cytokine with various actions including the selective killing of tumor cells; toxicity may be the result of the production of free radicals following the binding of high-affinity cell surface receptors.
tumor-specific transplantation antigen (TSTA): Antigens uniquely expressed by certain tumor cells.
tyrosine kinases: A family of enzymes which phosphorylates proteins on tyrosine residues, a critical step in lymphocyte activation. The key tyrosine kinases in T-cell activation are Lck, Fyn, and ZAP-70; those in B-cell activation are Blk, Fyn, Lyn, and Syk.
unresponsiveness: Inability to respond to antigenic stimulus. Unresponsiveness may be specific for a particular antigen (see Tolerance), or broadly nonspecific as a result of damage to the entire immune system, for example, after whole-body irradiation.
V regions: See variable regions.
V(D)J recombination: Mechanism for generating antigen-specific receptors of T and B cells; it involves the joining of V, D, and J gene segments mediated by the enzyme complex V(D)J recombinase, and products of the RAG-1 and 2 genes.
vaccination: Any protective immunization against a pathogen. Originally referred to immunization against smallpox with the less virulent cowpox (vaccinia) virus.
variable (V) regions: The N-terminal portion of an Ig or TCR which contains the antigen-binding region of the molecule; V regions are formed by the recombination of V(D) and J gene segments.
virion: A complete virus particle.
virus: An organism comprising a protein coat and DNA or RNA genome; it requires a host cell for replication.
Western blotting: A technique to identify a specific protein in a mixture; proteins separated by gel electrophoresis are blotted onto a nitrocellulose membrane, and the protein of interest is detected by adding radiolabeled antibody specific for the protein.
wheal and flare: Itchy reaction at skin site where antigen is injected into an allergic individual; characterized by erythema (redness due to dilation of blood vessels) and edema (swelling produced by release of serum into tissue).
xenogeneic: Originating from a foreign species.
xenograft: A tissue transplantation between individuals belonging to two different species.
X-linked agammaglobulinemia: Disease in boys manifesting as absence of mature B cells; due to defective tyrosine kinase btk, B cell differentiation does not progress beyond pre-B cell.
X-linked hyper-IgM syndrome: Disease in boys manifesting as inability to synthesize Ig isotypes other than IgM; result of defect in either CD40 or CD154.
ZAP-70: A T-cell specific tyrosine kinase involved in T cell activation.