Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Antibody Specificity: The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.Antibodies, Viral: Immunoglobulins produced in response to VIRAL ANTIGENS.Antibodies, Bacterial: Immunoglobulins produced in a response to BACTERIAL ANTIGENS.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Antibody Formation: The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.Antibodies, Neutralizing: Antibodies that reduce or abolish some biological activity of a soluble antigen or infectious agent, usually a virus.Antibody Affinity: A measure of the binding strength between antibody and a simple hapten or antigen determinant. It depends on the closeness of stereochemical fit between antibody combining sites and antigen determinants, on the size of the area of contact between them, and on the distribution of charged and hydrophobic groups. It includes the concept of "avidity," which refers to the strength of the antigen-antibody bond after formation of reversible complexes.Fluorescent Antibody Technique: Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.Antibodies, Anti-Idiotypic: Antibodies which react with the individual structural determinants (idiotopes) on the variable region of other antibodies.Binding Sites, Antibody: Local surface sites on antibodies which react with antigen determinant sites on antigens (EPITOPES.) They are formed from parts of the variable regions of FAB FRAGMENTS.HIV Antibodies: Antibodies reactive with HIV ANTIGENS.Epitopes: Sites on an antigen that interact with specific antibodies.Antibodies, Neoplasm: Immunoglobulins induced by antigens specific for tumors other than the normally occurring HISTOCOMPATIBILITY ANTIGENS.Antibodies, Protozoan: Immunoglobulins produced in a response to PROTOZOAN ANTIGENS.Antibodies, Antinuclear: Autoantibodies directed against various nuclear antigens including DNA, RNA, histones, acidic nuclear proteins, or complexes of these molecular elements. Antinuclear antibodies are found in systemic autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, polymyositis, and mixed connective tissue disease.Cross Reactions: Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.Immunoglobulin M: A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.Autoantibodies: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.Antibodies, Fungal: Immunoglobulins produced in a response to FUNGAL ANTIGENS.Neutralization Tests: The measurement of infection-blocking titer of ANTISERA by testing a series of dilutions for a given virus-antiserum interaction end-point, which is generally the dilution at which tissue cultures inoculated with the serum-virus mixtures demonstrate cytopathology (CPE) or the dilution at which 50% of test animals injected with serum-virus mixtures show infectivity (ID50) or die (LD50).Antigen-Antibody Reactions: The processes triggered by interactions of ANTIBODIES with their ANTIGENS.Antibodies, Bispecific: Antibodies, often monoclonal, in which the two antigen-binding sites are specific for separate ANTIGENIC DETERMINANTS. They are artificial antibodies produced by chemical crosslinking, fusion of HYBRIDOMA cells, or by molecular genetic techniques. They function as the main mediators of targeted cellular cytotoxicity and have been shown to be efficient in the targeting of drugs, toxins, radiolabeled haptens, and effector cells to diseased tissue, primarily tumors.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Single-Chain Antibodies: A form of antibodies consisting only of the variable regions of the heavy and light chains (FV FRAGMENTS), connected by a small linker peptide. They are less immunogenic than complete immunoglobulin and thus have potential therapeutic use.Mice, Inbred BALB CAntibodies, Blocking: Antibodies that inhibit the reaction between ANTIGEN and other antibodies or sensitized T-LYMPHOCYTES (e.g., antibodies of the IMMUNOGLOBULIN G class that compete with IGE antibodies for antigen, thereby blocking an allergic response). Blocking antibodies that bind tumors and prevent destruction of tumor cells by CYTOTOXIC T-LYMPHOCYTES have also been called enhancing antibodies. (Rosen et al., Dictionary of Immunology, 1989)Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.Immunoglobulin Fab Fragments: Univalent antigen-binding fragments composed of one entire IMMUNOGLOBULIN LIGHT CHAIN and the amino terminal end of one of the IMMUNOGLOBULIN HEAVY CHAINS from the hinge region, linked to each other by disulfide bonds. Fab contains the IMMUNOGLOBULIN VARIABLE REGIONS, which are part of the antigen-binding site, and the first IMMUNOGLOBULIN CONSTANT REGIONS. This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.Antibodies, Heterophile: Antibodies elicited in a different species from which the antigen originated. These antibodies are directed against a wide variety of interspecies-specific antigens, the best known of which are Forssman, Hanganutziu-Deicher (H-D), and Paul-Bunnell (P-B). Incidence of antibodies to these antigens--i.e., the phenomenon of heterophile antibody response--is useful in the serodiagnosis, pathogenesis, and prognosis of infection and latent infectious states as well as in cancer classification.Antibodies, Catalytic: Antibodies that can catalyze a wide variety of chemical reactions. They are characterized by high substrate specificity and share many mechanistic features with enzymes.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Immunoglobulin A: Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory IgA (IMMUNOGLOBULIN A, SECRETORY) is the main immunoglobulin in secretions.Antibodies, Monoclonal, Humanized: Antibodies from non-human species whose protein sequences have been modified to make them nearly identical with human antibodies. If the constant region and part of the variable region are replaced, they are called humanized. If only the constant region is modified they are called chimeric. INN names for humanized antibodies end in -zumab.Fluorescent Antibody Technique, Indirect: A form of fluorescent antibody technique commonly used to detect serum antibodies and immune complexes in tissues and microorganisms in specimens from patients with infectious diseases. The technique involves formation of an antigen-antibody complex which is labeled with fluorescein-conjugated anti-immunoglobulin antibody. (From Bennington, Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984)Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure MONOCLONAL ANTIBODIES or T-cell products, identical to those produced by the immunologically competent parent cell.Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by ANTIGEN injection or infection with microorganisms containing the antigen.Epitope Mapping: Methods used for studying the interactions of antibodies with specific regions of protein antigens. Important applications of epitope mapping are found within the area of immunochemistry.Antibodies, Antiphospholipid: Autoantibodies directed against phospholipids. These antibodies are characteristically found in patients with systemic lupus erythematosus (LUPUS ERYTHEMATOSUS, SYSTEMIC;), ANTIPHOSPHOLIPID SYNDROME; related autoimmune diseases, some non-autoimmune diseases, and also in healthy individuals.Immunization: Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).Antigens: Substances that are recognized by the immune system and induce an immune reaction.Immunoenzyme Techniques: Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Antigens, Bacterial: Substances elaborated by bacteria that have antigenic activity.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Antigens, Surface: Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.Immunization, Passive: Transfer of immunity from immunized to non-immune host by administration of serum antibodies, or transplantation of lymphocytes (ADOPTIVE TRANSFER).Recombinant Proteins: Proteins prepared by recombinant DNA technology.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Immunoassay: A technique using antibodies for identifying or quantifying a substance. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance.Immunoglobulin Fragments: Partial immunoglobulin molecules resulting from selective cleavage by proteolytic enzymes or generated through PROTEIN ENGINEERING techniques.Molecular Weight: The sum of the weight of all the atoms in a molecule.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Antigens, Viral: Substances elaborated by viruses that have antigenic activity.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Non-immunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.B-Lymphocytes: Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.Complement Fixation Tests: Serologic tests based on inactivation of complement by the antigen-antibody complex (stage 1). Binding of free complement can be visualized by addition of a second antigen-antibody system such as red cells and appropriate red cell antibody (hemolysin) requiring complement for its completion (stage 2). Failure of the red cells to lyse indicates that a specific antigen-antibody reaction has taken place in stage 1. If red cells lyse, free complement is present indicating no antigen-antibody reaction occurred in stage 1.Hemagglutination Tests: Sensitive tests to measure certain antigens, antibodies, or viruses, using their ability to agglutinate certain erythrocytes. (From Stedman, 26th ed)Hemagglutination Inhibition Tests: Serologic tests in which a known quantity of antigen is added to the serum prior to the addition of a red cell suspension. Reaction result is expressed as the smallest amount of antigen which causes complete inhibition of hemagglutination.Antibodies, Antineutrophil Cytoplasmic: Autoantibodies directed against cytoplasmic constituents of POLYMORPHONUCLEAR LEUKOCYTES and/or MONOCYTES. They are used as specific markers for GRANULOMATOSIS WITH POLYANGIITIS and other diseases, though their pathophysiological role is not clear. ANCA are routinely detected by indirect immunofluorescence with three different patterns: c-ANCA (cytoplasmic), p-ANCA (perinuclear), and atypical ANCA.Immunoglobulin Variable Region: That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions.Seroepidemiologic Studies: EPIDEMIOLOGIC STUDIES based on the detection through serological testing of characteristic change in the serum level of specific ANTIBODIES. Latent subclinical infections and carrier states can thus be detected in addition to clinically overt cases.Immunoglobulin Idiotypes: Unique genetically-controlled determinants present on ANTIBODIES whose specificity is limited to a single group of proteins (e.g., another antibody molecule or an individual myeloma protein). The idiotype appears to represent the antigenicity of the antigen-binding site of the antibody and to be genetically codetermined with it. The idiotypic determinants have been precisely located to the IMMUNOGLOBULIN VARIABLE REGION of both immunoglobin polypeptide chains.T-Lymphocytes: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.Immunologic Techniques: Techniques used to demonstrate or measure an immune response, and to identify or measure antigens using antibodies.Antigens, Neoplasm: Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Immunosorbent Techniques: Techniques for removal by adsorption and subsequent elution of a specific antibody or antigen using an immunosorbent containing the homologous antigen or antibody.Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response.Antibody Diversity: The phenomenon of immense variability characteristic of ANTIBODIES. It enables the IMMUNE SYSTEM to react specifically against the essentially unlimited kinds of ANTIGENS it encounters. Antibody diversity is accounted for by three main theories: (1) the Germ Line Theory, which holds that each antibody-producing cell has genes coding for all possible antibody specificities, but expresses only the one stimulated by antigen; (2) the Somatic Mutation Theory, which holds that antibody-producing cells contain only a few genes, which produce antibody diversity by mutation; and (3) the Gene Rearrangement Theory, which holds that antibody diversity is generated by the rearrangement of IMMUNOGLOBULIN VARIABLE REGION gene segments during the differentiation of the ANTIBODY-PRODUCING CELLS.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Peptide Library: A collection of cloned peptides, or chemically synthesized peptides, frequently consisting of all possible combinations of amino acids making up an n-amino acid peptide.Hepatitis C Antibodies: Antibodies to the HEPATITIS C ANTIGENS including antibodies to envelope, core, and non-structural proteins.Isoantibodies: Antibodies from an individual that react with ISOANTIGENS of another individual of the same species.Immunoglobulin Isotypes: The classes of immunoglobulins found in any species of animal. In man there are nine classes that migrate in five different groups in electrophoresis; they each consist of two light and two heavy protein chains, and each group has distinguishing structural and functional properties.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Immunoglobulins: Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.Antibodies, Monoclonal, Murine-Derived: Antibodies obtained from a single clone of cells grown in mice or rats.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Hepatitis B Antibodies: Antibodies to the HEPATITIS B ANTIGENS, including antibodies to the surface (Australia) and core of the Dane particle and those to the "e" antigens.Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction.Sensitivity and Specificity: Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)Binding, Competitive: The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Immunity, Maternally-Acquired: Resistance to a disease-causing agent induced by the introduction of maternal immunity into the fetus by transplacental transfer or into the neonate through colostrum and milk.Insulin Antibodies: Antibodies specific to INSULIN.Complement System Proteins: Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).Lupus Erythematosus, Systemic: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.Spleen: An encapsulated lymphatic organ through which venous blood filters.Autoantigens: Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.Mice, Inbred C57BLRecombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Precipitin Tests: Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.Species Specificity: The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.Antigens, Protozoan: Any part or derivative of any protozoan that elicits immunity; malaria (Plasmodium) and trypanosome antigens are presently the most frequently encountered.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Serologic Tests: Diagnostic procedures involving immunoglobulin reactions.Antibody-Dependent Cell Cytotoxicity: The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface IMMUNOGLOBULIN G whose Fc portion is intact. The effector cell is a "killer" cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent.Single-Domain Antibodies: An immunoglobulin fragment composed of one variable domain from an IMMUNOGLOBULIN HEAVY CHAIN or IMMUNOGLOBULIN LIGHT CHAIN.Polysaccharides, Bacterial: Polysaccharides found in bacteria and in capsules thereof.Kinetics: The rate dynamics in chemical or physical systems.Chromatography, Affinity: A chromatographic technique that utilizes the ability of biological molecules to bind to certain ligands specifically and reversibly. It is used in protein biochemistry. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Iodine Radioisotopes: Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes.Bacterial Vaccines: Suspensions of attenuated or killed bacteria administered for the prevention or treatment of infectious bacterial disease.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Mice, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Immunochemistry: Field of chemistry that pertains to immunological phenomena and the study of chemical reactions related to antigen stimulation of tissues. It includes physicochemical interactions between antigens and antibodies.Viral Envelope Proteins: Layers of protein which surround the capsid in animal viruses with tubular nucleocapsids. The envelope consists of an inner layer of lipids and virus specified proteins also called membrane or matrix proteins. The outer layer consists of one or more types of morphological subunits called peplomers which project from the viral envelope; this layer always consists of glycoproteins.Immunoglobulin Heavy Chains: The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kDa.Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.Dose-Response Relationship, Immunologic: A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.Autoimmune Diseases: Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.Antigens, CD: Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (IMMUNOTOXINS) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (see RADIOTHERAPY).Lymphocyte Activation: Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.Viral Vaccines: Suspensions of attenuated or killed viruses administered for the prevention or treatment of infectious viral disease.Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera.Microscopy, Electron: Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.Immunoglobulin E: An immunoglobulin associated with MAST CELLS. Overexpression has been associated with allergic hypersensitivity (HYPERSENSITIVITY, IMMEDIATE).Epitopes, B-Lymphocyte: Antigenic determinants recognized and bound by the B-cell receptor. Epitopes recognized by the B-cell receptor are located on the surface of the antigen.Immunoglobulin Light Chains: Polypeptide chains, consisting of 211 to 217 amino acid residues and having a molecular weight of approximately 22 kDa. There are two major types of light chains, kappa and lambda. Two Ig light chains and two Ig heavy chains (IMMUNOGLOBULIN HEAVY CHAINS) make one immunoglobulin molecule.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Agglutination Tests: Tests that are dependent on the clumping of cells, microorganisms, or particles when mixed with specific antiserum. (From Stedman, 26th ed)Vaccines, Synthetic: Small synthetic peptides that mimic surface antigens of pathogens and are immunogenic, or vaccines manufactured with the aid of recombinant DNA techniques. The latter vaccines may also be whole viruses whose nucleic acids have been modified.Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection.Swine: Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).Microscopy, Immunoelectron: Microscopy in which the samples are first stained immunocytochemically and then examined using an electron microscope. Immunoelectron microscopy is used extensively in diagnostic virology as part of very sensitive immunoassays.HIV-1: The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Immunotoxins: Semisynthetic conjugates of various toxic molecules, including RADIOACTIVE ISOTOPES and bacterial or plant toxins, with specific immune substances such as IMMUNOGLOBULINS; MONOCLONAL ANTIBODIES; and ANTIGENS. The antitumor or antiviral immune substance carries the toxin to the tumor or infected cell where the toxin exerts its poisonous effect.Antiphospholipid Syndrome: The presence of antibodies directed against phospholipids (ANTIBODIES, ANTIPHOSPHOLIPID). The condition is associated with a variety of diseases, notably systemic lupus erythematosus and other connective tissue diseases, thrombopenia, and arterial or venous thromboses. In pregnancy it can cause abortion. Of the phospholipids, the cardiolipins show markedly elevated levels of anticardiolipin antibodies (ANTIBODIES, ANTICARDIOLIPIN). Present also are high levels of lupus anticoagulant (LUPUS COAGULATION INHIBITOR).Radioimmunodetection: Use of radiolabeled antibodies for diagnostic imaging of neoplasms. Antitumor antibodies are labeled with diverse radionuclides including iodine-131, iodine-123, indium-111, or technetium-99m and injected into the patient. Images are obtained by a scintillation camera.Chickens: Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.HIV Envelope Protein gp120: External envelope protein of the human immunodeficiency virus which is encoded by the HIV env gene. It has a molecular weight of 120 kDa and contains numerous glycosylation sites. Gp120 binds to cells expressing CD4 cell-surface antigens, most notably T4-lymphocytes and monocytes/macrophages. Gp120 has been shown to interfere with the normal function of CD4 and is at least partly responsible for the cytopathic effect of HIV.Cell Adhesion: Adherence of cells to surfaces or to other cells.beta 2-Glycoprotein I: A 44-kDa highly glycosylated plasma protein that binds phospholipids including CARDIOLIPIN; APOLIPOPROTEIN E RECEPTOR; membrane phospholipids, and other anionic phospholipid-containing moieties. It plays a role in coagulation and apoptotic processes. Formerly known as apolipoprotein H, it is an autoantigen in patients with ANTIPHOSPHOLIPID ANTIBODIES.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Immunoglobulin A, Secretory: The principle immunoglobulin in exocrine secretions such as milk, respiratory and intestinal mucin, saliva and tears. The complete molecule (around 400 kD) is composed of two four-chain units of IMMUNOGLOBULIN A, one SECRETORY COMPONENT and one J chain (IMMUNOGLOBULIN J-CHAINS).HemocyaninFluorescent Antibody Technique, Direct: A form of fluorescent antibody technique utilizing a fluorochrome conjugated to an antibody, which is added directly to a tissue or cell suspension for the detection of a specific antigen. (Bennington, Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984)Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Tetanus ToxoidAdjuvants, Immunologic: Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.Bacterial Proteins: Proteins found in any species of bacterium.Goats: Any of numerous agile, hollow-horned RUMINANTS of the genus Capra, in the family Bovidae, closely related to the SHEEP.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Rheumatoid Factor: Antibodies found in adult RHEUMATOID ARTHRITIS patients that are directed against GAMMA-CHAIN IMMUNOGLOBULINS.Immunity, Humoral: Antibody-mediated immune response. Humoral immunity is brought about by ANTIBODY FORMATION, resulting from TH2 CELLS activating B-LYMPHOCYTES, followed by COMPLEMENT ACTIVATION.Immunization, Secondary: Any immunization following a primary immunization and involving exposure to the same or a closely related antigen.Bacterial Outer Membrane Proteins: Proteins isolated from the outer membrane of Gram-negative bacteria.Viral Proteins: Proteins found in any species of virus.Pregnancy: The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.Immunoglobulin Fc Fragments: Crystallizable fragments composed of the carboxy-terminal halves of both IMMUNOGLOBULIN HEAVY CHAINS linked to each other by disulfide bonds. Fc fragments contain the carboxy-terminal parts of the heavy chain constant regions that are responsible for the effector functions of an immunoglobulin (COMPLEMENT fixation, binding to the cell membrane via FC RECEPTORS, and placental transport). This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Sheep: Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.Protozoan Proteins: Proteins found in any species of protozoan.Mice, Nude: Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.Cell Line, Tumor: A cell line derived from cultured tumor cells.Receptors, Fc: Molecules found on the surface of some, but not all, B-lymphocytes, T-lymphocytes, and macrophages, which recognize and combine with the Fc (crystallizable) portion of immunoglobulin molecules.Immunity, Cellular: Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Opsonin Proteins: Proteins that bind to particles and cells to increase susceptibility to PHAGOCYTOSIS, especially ANTIBODIES bound to EPITOPES that attach to FC RECEPTORS. COMPLEMENT C3B may also participate.Indium Radioisotopes: Unstable isotopes of indium that decay or disintegrate emitting radiation. In atoms with atomic weights 106-112, 113m, 114, and 116-124 are radioactive indium isotopes.Antibody-Producing Cells: Cells of the lymphoid series that can react with antigen to produce specific cell products called antibodies. Various cell subpopulations, often B-lymphocytes, can be defined, based on the different classes of immunoglobulins that they synthesize.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Staining and Labeling: The marking of biological material with a dye or other reagent for the purpose of identifying and quantitating components of tissues, cells or their extracts.Gangliosides: A subclass of ACIDIC GLYCOSPHINGOLIPIDS. They contain one or more sialic acid (N-ACETYLNEURAMINIC ACID) residues. Using the Svennerholm system of abbrevations, gangliosides are designated G for ganglioside, plus subscript M, D, or T for mono-, di-, or trisialo, respectively, the subscript letter being followed by a subscript arabic numeral to indicated sequence of migration in thin-layer chromatograms. (From Oxford Dictionary of Biochemistry and Molecular Biology, 1997)Lipopolysaccharides: Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)Evaluation Studies as Topic: Studies determining the effectiveness or value of processes, personnel, and equipment, or the material on conducting such studies. For drugs and devices, CLINICAL TRIALS AS TOPIC; DRUG EVALUATION; and DRUG EVALUATION, PRECLINICAL are available.Protein Engineering: Procedures by which protein structure and function are changed or created in vitro by altering existing or synthesizing new structural genes that direct the synthesis of proteins with sought-after properties. Such procedures may include the design of MOLECULAR MODELS of proteins using COMPUTER GRAPHICS or other molecular modeling techniques; site-specific mutagenesis (MUTAGENESIS, SITE-SPECIFIC) of existing genes; and DIRECTED MOLECULAR EVOLUTION techniques to create new genes.Hemolytic Plaque Technique: A method to identify and enumerate cells that are synthesizing ANTIBODIES against ANTIGENS or HAPTENS conjugated to sheep RED BLOOD CELLS. The sheep red blood cells surrounding cells secreting antibody are lysed by added COMPLEMENT producing a clear zone of HEMOLYSIS. (From Illustrated Dictionary of Immunology, 3rd ed)Receptors, Cell Surface: Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Radioimmunoprecipitation Assay: Sensitive assay using radiolabeled ANTIGENS to detect specific ANTIBODIES in SERUM. The antigens are allowed to react with the serum and then precipitated using a special reagent such as PROTEIN A sepharose beads. The bound radiolabeled immunoprecipitate is then commonly analyzed by gel electrophoresis.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Cattle Diseases: Diseases of domestic cattle of the genus Bos. It includes diseases of cows, yaks, and zebus.Camelids, New World: Ruminant mammals of South America. They are related to camels.Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.Cytotoxicity, Immunologic: The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.Antigens, CD20: Unglycosylated phosphoproteins expressed only on B-cells. They are regulators of transmembrane Ca2+ conductance and thought to play a role in B-cell activation and proliferation.Rubella virus: The type (and only) species of RUBIVIRUS causing acute infection in humans, primarily children and young adults. Humans are the only natural host. A live, attenuated vaccine is available for prophylaxis.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.

Plaque-forming cells in mice after experimental infection with Brucella abortus. (1/1095)

Cells producing antibody to brucella lipopolysaccharide were detected in spleens of mice infected with Brucella abortus 19 by a hemolytic plaque assay. The appearance of immunoglobulin M-producing cells preceded humoral antibodies. The primary plaques were observed 5 days after inoculation, and they were still present by day 70.  (+info)

Induction of mucosal immunity by inactivated poliovirus vaccine is dependent on previous mucosal contact with live virus. (2/1095)

The inactivated poliovirus vaccine (IPV) is used for protection against poliomyelitis in The Netherlands. It is not clear, however, whether IPV vaccination can lead to priming of the mucosal immune system and the induction of IgA. It has been demonstrated that IPV vaccination is able to induce strong memory IgA responses in the serum of persons who have been naturally exposed to wild-type poliovirus. This has led to the hypothesis that IPV vaccination is able to induce poliovirus-specific IgA at mucosal sites in persons who have been previously primed with live poliovirus at mucosal sites. To test this hypothesis, the kinetics of the IgA response in serum and saliva after IPV vaccination were examined in persons previously vaccinated with oral poliovirus vaccine (OPV) or IPV. ELISA and enzyme-linked immunospot assays were used for the detection of poliovirus-specific IgA responses. In addition, B cell populations were separated on the basis of the expression of mucosal (alpha4beta7 integrin) and peripheral homing receptors (L-selectin). Parenteral IPV vaccination was able to boost systemic and mucosal IgA responses in previously OPV-vaccinated persons only. None of the previously vaccinated IPV recipients responded with the production of IgA in saliva. In agreement with this finding, a large percentage of the poliovirus-specific IgA-producing lymphocytes detected in previous OPV recipients expressed the alpha4beta7 integrin. It is concluded that IPV vaccination alone is insufficient to induce a mucosal IgA response against poliovirus. In mucosally (OPV-) primed individuals, however, booster vaccination with IPV leads to a strong mucosal IgA response.  (+info)

Characterization of anergic anti-DNA B cells: B cell anergy is a T cell-independent and potentially reversible process. (3/1095)

Anti-single stranded DNA (ssDNA) and anti-double stranded DNA (dsDNA) B cells are regulated in non-autoimmune mice. In this report we show that while both anti-ssDNA and anti-dsDNA B cells are blocked in their ability to differentiate into antibody-secreting cells, other phenotypic and functional characteristics distinguish them from one another. Splenic anti-ssDNA B cells are found distributed throughout the B cell follicle, and are phenotypically mature and long-lived. On the other hand, splenic anti-dsDNA B cells are short-lived, exhibit an immature and antigen-experienced phenotype, and localize to the T-B interface of the splenic follicle. Functionally, anti-ssDNA B cells proliferate, albeit suboptimally, in response to anti-IgM, lipopolysaccharide (LPS) and CD40L/IL-4 + anti-IgM stimulation, and tyrosine phosphorylate intracellular proteins upon mIgM cross-linking. Anti-dsDNA B cells, on the other hand, are functionally unresponsive to anti-IgM and LPS stimulation, and do not phosphorylate intracellular proteins, including Syk, upon mIg stimulation. Importantly, anti-DNA B cell anergy is maintained in the absence of T cells since both anti-ssDNA and anti-dsDNA B cells are as efficiently regulated in RAG2(-/-) mice as in their RAG2(+/+) counterparts. Interestingly, the severely anergic state of anti-dsDNA B cells is partially reversible upon stimulation with CD40 ligand and IL-4. In response to these signals, anti-dsDNA B cells remain viable, up-regulate cell surface expression of B7-2 and IgM, and restore their ability to proliferate and phosphorylate Syk upon mIg cross-linking. Collectively, these data suggest that anti-DNA B cell anergy encompasses distinct phenotypes which, even in its most severe form, may be reversible upon stimulation with T cell-derived factors.  (+info)

Development of immunoglobulin and antibody-synthesizing cells after immunization with different doses of antigen. (4/1095)

The kinetics of development of antibody-synthesizing cells and of cells synthesizing immunoglobulins without detectable antibody function were studied in rats immunized with different doses (0-1, 1, 10, 100 mg) of horse radish peroxidase, bovine serum albumin, human serum albumin, hen ovalbumin, or human IgG, which had been deaggregated or heat-aggregated. Each antigen was injected once or twice as a solution in saline. Antibody and immunoglobulin-producing cells were detected in draining lymph nodes by immunohistochemical staining. In the primary response a few antibody-synthesizing cells were found whatever the dose injected. No increase or some increase was found with the amount of antigen injected, according to the protein used, but with all doses of antigen injected, the population of cells remained small, except with human IgG where a relatively high number of positive cells was detected even after injection of 1 mg of antigen. In the secondary response a few antibody-forming cells were also detected with the lower doses of antigen, but this population increased after boosting with 100 mg of antigen. With human IgG a greater number of positive cells was induced withall the doses tested. A correlation between the number of cells synthesizing immunoglobulins without antibody function and the amount of antigen injected was observed in the primary and secondary responses. The relative size of these two populations varied with the stage of immunity of the animals. In the primary response, the population of cells synthesizing immunoglobulins without antibody function was larger than the population of antibody-forming cells. The same was true in the secondary response, but if after a booster injection the level of antibody-synthesizing cells exceeded that reached in the primary response, the increase of cells synthesizing Ig without antibody function was smaller than the increase in antibody-forming cells. In general the more immunogenic an antigen was, the smaller was the ratio between antibody-forming cells and cells producing immunoglobulin without antibody function.  (+info)

Differential involvement of the transcription factor Blimp-1 in T cell-independent and -dependent B cell differentiation to plasma cells. (5/1095)

Along humoral immune responses, different stimuli drive the differentiation of B lymphocytes to Ig-secreting plasma cells in discrete microenvironments. The Blimp-1 transcription factor is up-regulated early during the transition of mature B cells to IgM-secreting plasma cells. In the present study, we have examined the requirement of Blimp-1 in plasma cell formation after both T cell-independent (LPS) and -dependent (CD40 + IL-4, Th cell lines) stimulation of spleen B cells. B lymphocyte-induced maturation protein (Blimp-1) was expressed early after in vitro LPS stimulation, mainly in a population of IgM+Syndecan+CD43+ preplasma cells. In contrast, the BSAP transcription factor expressed in mature B cells was down-regulated during the differentiation to plasma cells. Treatment of these cultures with Blimp-1-specific antisense phosphorothioate oligonucleotides suppressed both Blimp-1 protein levels and the emergence of IgM+Syndecan+ cells and plasma cells. However, T-B cell cocultures of spleen B cells from C3H/HeJ (H-2k) mice and syngeneic autoreactive SR.10 Th2 cells submitted to the anti-Blimp-1 therapy did not show any significant reduction in IgM- and IgG1-secreting plasma cell formation. Spleen B cells treated with anti-CD40 mAb + IL-4 differentiated to IgG1-secreting cells without significant transcription of the Blimp-1 gene; anti-Blimp-1 treatment subsequently did not have any effect in the later cultures. Altogether, these results suggest that Blimp-1 transcription factor specifically promotes T cell-independent B cell differentiation to plasma cells, probably at preplasma cell stages. In contrast, T cell-dependent plasma cell formation likely evolves through Blimp-1-independent pathways.  (+info)

Relaxed negative selection in germinal centers and impaired affinity maturation in bcl-xL transgenic mice. (6/1095)

The role of apoptosis in affinity maturation was investigated by determining the affinity of (4-hydroxy-3-nitrophenyl)acetyl (NP)-specific antibody-forming cells (AFCs) and serum antibody in transgenic mice that overexpress a suppressor of apoptosis, Bcl-xL, in the B cell compartment. Although transgenic animals briefly expressed higher numbers of splenic AFCs after immunization, the bcl-xL transgene did not increase the number or size of germinal centers (GCs), alter the levels of serum antibody, or change the frequency of NP-specific, long-lived AFCs. Nonetheless, the bcl-xL transgene product, in addition to endogenous Bcl-xL, reduced apoptosis in GC B cells and resulted in the expansion of B lymphocytes bearing VDJ rearrangements that are usually rare in primary anti-NP responses. Long-lived AFCs bearing these noncanonical rearrangements were frequent in the bone marrow and secreted immunoglobulin G(1) antibodies with low affinity for NP. The abundance of noncanonical cells lowered the average affinity of long-lived AFCs and serum antibody, demonstrating that Bcl-xL and apoptosis influence clonal selection/maintenance for affinity maturation.  (+info)

Partial IgA-deficiency with increased Th2-type cytokines in TGF-beta 1 knockout mice. (7/1095)

Though it has been shown that TGF-beta 1 directs B cells to switch to IgA in vitro, no studies have assessed TGF-beta 1 effects on mucosal vs systemic immunity in vivo. When the B cell functions of TGF-beta 1 gene-disrupted (TGF-beta 1-/-) mice were analyzed, significantly decreased IgA levels and increased IgG and IgM levels in serum and external secretions were observed. Further, analysis of Ab forming cells (AFC) isolated from both mucosal and systemic lymphoid tissue showed elevated IgM, IgG, and IgE, with decreased IgA AFC. A lack of IgA-committed B cells was seen in TGF-beta 1-/- mice, especially in the gastrointestinal (GI) tract. Splenic T cells triggered via the TCR expressed elevated Th2-type cytokines and, consistent with this observation, a 31-fold increase in serum IgE was seen in TGF-beta 1-/- mice. Thus, uncontrolled B cell responses, which include elevated IgE levels, a lack of antiinflammatory IgA, and an excess of complement-binding IgG and IgM Abs, will promote inflammation at mucosal surfaces in TGF-beta 1-/- mice and likely contribute to pulmonary and GI tract lesions, ultimately leading to the early death of these mice.  (+info)

Variegated expression of the endogenous immunoglobulin heavy-chain gene in the absence of the intronic locus control region. (8/1095)

The expression of chromosomally integrated transgenes usually varies greatly among independent transfectants. This variability in transgene expression has led to the definition of locus control regions (LCRs) as elements which render expression consistent. Analyses of expression in single cells revealed that the expression of transgenes which lack an LCR is often variegated, i.e., on in some cells and off in others. In many cases, transgenes which show variegated expression were found to have inserted near the centromere. These observations have suggested that the LCR prevents variegation by blocking the inhibitory effect of heterochromatin and other repetitive-DNA-containing structures at the insertion site and have raised the question of whether the LCR plays a similar role in endogenous genes. To address this question, we have examined the effects of deleting the LCR from the immunoglobulin heavy-chain locus of a mouse hybridoma cell line in which expression of the immunoglobulin mu heavy-chain gene is normally highly stable. Our analysis of mu expression in single cells shows that deletion of this LCR resulted in variegated expression of the mu gene. That is, in the absence of the LCR, expression of the mu gene in the recombinant locus could be found in either of two epigenetically maintained, metastable states, in which transcription occurred either at the normal rate or not at all. In the absence of the LCR, the on state had a half-life of approximately 100 cell divisions, while the half-life of the off state was approximately 40,000 cell divisions. For recombinants with an intact LCR, the half-life of the on state exceeded 50,000 cell divisions. Our results thus indicate that the LCR increased the stability of the on state by at least 500-fold.  (+info)

  • Although studies investigating the nature of Ab-secreting cells (ASCs) during acute infection with influenza or dengue virus found that the ASC response was dominated by virus-specific IgG secretion, the Ag specificity and phenotype of ASCs during primary acute viral infection were not identified. (
  • As compared with HAV-specific ASCs, non-HAV-specific ASCs were Ki-67 low CD138 high CD31 high CD38 high , demonstrating that non-HAV-specific ASCs had a bone marrow plasma cell-like phenotype whereas HAV-specific ASCs had a phenotype typical of circulating plasmablasts. (
  • These data suggest that non-HAV-specific ASCs might be mobilized plasma cells from the bone marrow or the spleen, whereas HAV-specific ASCs were newly generated plasmablasts. (
  • Our lab is currently focused on (1) identifying optimal conditions for differentiation of engineered human B cells into long-lived antibody-secreting cells, (2) assessing the impact of autophagy on plasma cell survival, and (3) determining the effect that a host immune system will have on engrafted engineered B cells. (
  • In this study, we provide evidence that pre-existing plasma cells are released into the circulation and contribute to Ag-nonspecific secretion of IgM during primary HAV infection. (
  • Naïve ( A and B ) and activated ( C and D ) T cells were assayed for their chemotactic response to serum samples obtained from patients undergoing therapy with trastuzumab and IL-12. (
  • E, migration of activated T cells was measured in response to patient serum that had been pretreated with neutralizing concentrations of antibodies to IL-8, RANTES, and MIP-1α or with isotype-matched control IgG. (
  • Here, we report the development of a serum-free CHO DG44 cell line, stably producing a CR9114-like antibody with a potential to become a useful influenza virus research tool. (
  • Here, we decided to take advantage of a biotechnology-relevant production cell line, Chinese hamster ovary (CHO) DG44, to establish a serum-free, stable, CR9114-like (CR9114L, a generic version of CR9114) antibody-producing cell line for a steady supply of this mAb with low batch to batch variation. (
  • However, the variation was only 2.3-fold for sequential serum samples from the same patient, indicating different distributions of terminal- versus internal-binding antibodies in different individuals. (
  • The Kelsoe group will analyze induction of germinal centers, Ig class switch recombination and hypermutation, affinity maturation of serum antibodies and germinal center B cells in response to MPER immunogens. (
  • Finally, the stable manufacture of fully non-fucosylated antibodies with enhanced ADCC was confirmed using the converted cells in serum-free fed-batch culture. (
  • Such antibodies may sometimes not be detected in recipient serum. (
  • Peripheral blood B cells were obtained from 36 subjects, including 16 allograft recipients, 12 sensitized patients, three multiparous women with serum HLA antibodies, and five healthy non-transfused male subjects. (
  • Beneficial effect of 30Kc6 gene expression on production of recombinant interferon-β in serum-free suspension culture of CHO cells", Process Biochemistry, Feb. 2009, vol. 44, pp. 146-153. (
  • In two cases, serum antibodies to Arg-hgp and Lys-hgp were AlphaScreen positive, whereas plasma cells were scarcely observed within the lesions. (
  • Isolation and characterization of antibodies in COVID-19 patients has largely focused on memory B cells , however it is the antibody-secreting plasma cells that are directly responsible for the production of serum antibodies , which play a critical role in controlling and resolving SARS-CoV-2 infection . (
  • Introduction: Naturally occurring antibodies (auto-Abs) recognizing human granulocyte-colony stimulating factor were detected with high frequency in serum samples obtained from umbilical cord blood of newborns (12 of 65 samples screened) and maternal peripheral blood serum samples from women at the end of gestation (seven of 56 cases tested). (
  • We now report that the antibodies produced by the B-cells within these clusters, as well as those in the serum of patients who were rejecting transplants, react strongly with the core carbohydrate epitopes of bacterial lipopolysaccharide (LPS). (
  • IL-21 production by CD4 + T cells is required for IL-6 to promote B cell antibody production in vitro. (
  • In particular, the methods relate to the field of in vitro monoclonal antibody production. (
  • In an attempt to learn about possible mechanisms, we investigated antibody production by recipient B lymphocytes in vitro. (
  • Materials and methods: Mononuclear cells from cord blood samples of different newborns containing high titer anti-G-CSF Abs were infected with Epstein-Barr virus in vitro, and EBV-immortalized B-cell lines were isolated and characterized for specific anti-G-CSF Ab production. (
  • Conclusion: The secreted Abs did not affect the in vitro generation of granulocyte colonies by human normal adult haemopoietic progenitor cells in soft agar clonogenic assays, suggesting that these Abs were not neutralizing. (
  • Thymidine (Tdr) and its analogues 5-fluorodeoxyuridine (FUdr) and 5-bromodeoxyuridine (BUdr) inhibited the development of antibody-producing cells (PFC) in cultures of explants of rabbit spleen stimulated with sheep red cells in vitro. (
  • For the method, use is made of in silico design synthetic immunogens, which are caused to act in vitro on human lymphocyte-containing cell populations. (
  • The results, published Tuesday, July 14 in Immunity , could provide vaccine designers with a goalpost when aiming for long-lasting antibody production. (
  • As described in part of the Immunity paper, the researchers studied 11 older individuals (aged 43 to 70) who had not been immunized against measles or mumps, but who had antibodies in their blood indicating infection by those viruses in childhood. (
  • In this way, antibodies help the body develop an immunity to disease. (
  • Antibodies are an essential component of our immune system, underpinning the effectiveness of both the primary immune response to microbial pathogens and the protective and long-lived immunity against. (
  • Plasma cell survival and the consequent duration of immunity vary widely with infection or vaccination. (
  • The progress of the disease may be broken down into three phases: an initial phase, characterized by a Type IV immune response (Cell-Mediated Immunity, delayed-hypersensitivity response), a second phase, characterized by a Type III response (Immune Complex), and a third phase where substantial tissue damage occurs. (
  • Lachmann outlines a scheme which attempts to account for most of the immunological findings in ROU and BS, and the shift from an early, predominantly lymphomonocytic infiltration (probably Type IV, cell- mediated immunity (CMI), delayed hypersensitivity) to a later PMNL infiltration with features associated with a Type III (immune complex) reaction. (
  • How herpesvirus-host interactions imprint on the immune system of otherwise healthy humans remains largely elusive, and contrary to the cellular immunity, the impact of EBV and CMV on the humoral immunity and B-cell compartment has received much less attention. (
  • Here the authors show that PRL-3 is also detectable on cell surface, and can be recognized by PRL3-zumab to recruit immune cells into tumor to promote anti-tumor immunity, thereby implicating PRL-3 as a potential tumor antigen. (
  • a key feature of this response is the production of antibodies by B cells (or B lymphocytes) involving an arm of the immune system known as humoral immunity . (
  • The benefit of this method of producing antibody is that it doesn't require initial infection, and through this route, many vaccinations confer immunity without causing illness. (
  • Their prophylactic and therapeutic protection ability was first discovered in the late nineteenth century by the passive transmission of antibodies from a diseased animal that provided immunity against diphtheria. (
  • an antibody-secreting cell, derived from B cells, that plays a major role in antibody-mediated immunity. (
  • Researchers in the U.S. have shown both preventive and treatment effects of an antibody cocktail in animal models of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - the agent that causes coronavirus disease 2019 (COVID-19). (
  • A small study published in the journal JCI Insight on November 14, 2019, suggests that antibody treatment could help people with severe allergy to peanuts eat a small amount of peanut-containing food just two weeks later, without any ill effects. (
  • Interestingly, humans have more memory B cells than mice 3,4 , although this may be an artifact of mice being housed in pathogen-free facilities and therefore, are exposed to only a limited number of microbes and infectious agents. (
  • Memory cells need to be recruited to lymph nodes if the infectious agent induces local inflammation. (
  • These cells defend the body against infection and disease by ingesting foreign materials and debris, by destroying infectious agents and cancer cells, or by producing antibodies (Britannica 1). (
  • Objective: To evaluate the frequency of anticardiolipin (aCL) or anti-beta-2 glycoprotein I (anti -β2GPI) antibodies in a cohort of patients with primary (PAPS) and secondary (SAPS) antiphospholipid syndrome and other rheumatic and infectious conditions. (
  • Using an antibody generated by the immune system of a recovered COVID-19 patient gives us a jump start on finding a safe and effective therapeutic," Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID) said in a statement. (
  • Yet with billions of dollars of research funds, all the infectious disease industry could do this flu season is produce a vaccine that was only 36% effective . (
  • Migration of naïve ( A ) or activated ( B ) T cells was measured in response to supernatants derived from costimulated NK cells (trastuzumab-coated tumor and IL-12) that had been preincubated with neutralizing concentrations of antibodies to MIP-1α, RANTES, and/or IL-8 or isotype-matched control antibodies ( Iso Ctl ). (
  • None of the HIV-1 reactive ileum antibodies were of the IgA isotype. (
  • Antibodies of the human IgG1 isotype containing two biantennary complex-type N -linked oligosaccharides in the constant region (Fc) [ 1 ] are commonly used therapeutically. (
  • Here, we present the first application of the Spec-seq framework, which we applied to human plasmablasts after influenza vaccination in order to characterize transcriptional differences governed by B cell receptor (BCR) isotype and vaccine reactivity. (
  • One very clever way to elicit production of antibody is to expose an individual to parts of a virus or bacterium without exposing them to the entire living pathogen. (
  • A preferred receptor is human CD152, particularly the regions of CDR1, CDR2 and CDR3 that elicit antibodies serving as antagonist, inverse agonist and agonist, respectively. (
  • MAb CR9114 is using the V H 1-69 germline gene and compared to other broadly neutralizing antibodies has a relatively small number of somatic mutations [ 1 ]. (
  • In recombinant cell lines, exogenous dhfr (together with the gene of interest, (GOI)) is provided by a vector used for transfection, making additional supplementation by HT unnecessary. (
  • It is from the CLP from which B cells arise (see Figure 1), commitment to the B cell lineage is a result of contact with the stromal cells as well as growth factor and cytokine production that results in initiating gene regulation that drives B cell commitment. (
  • Once HC Ig gene rearrangement has successfully initiated, the cells become precursor B (or pre-B) cells. (
  • During the pre-B cell stage (which can be divided into different phases) HC Ig gene rearrangement is completed and tested (I'll get back to this in a moment) and light chain (LC) gene rearrangement takes place to generate a fully functional B cell receptor (BCR, which is a membrane bound antibody). (
  • Once the LC gene is rearranged and produced it also must pair with the HC and be transported to the plasma membrane and interact with all the appropriate components signaling a fully formed BCR. (
  • Our scientists have years of experience at performing gene editing with CRISPR/Cas9, and have generated series of gene knockout CHO-K1 cell lines developed by CRISPR/Cas9 system. (
  • Our gene editing CHO-K1 cells can save your precious time and effort with great performance in antibody production. (
  • In 1982, researchers discovered an oncogene (a gene that can release cells from growth constraints, possibly converting them into tumors) in 90% of patients with Burkitt's lymphoma. (
  • The C- myc onco-gene appears to stimulate the HMG-I/Y gene, which then triggers the changes in normal B-cells that cause them to multiply rapidly and form tumors. (
  • The CAR gene is added to your T cells. (
  • Because viruses deliver DNA into human cells they are invaluable to gene therapists. (
  • TRA-8, an agonistic mouse monoclonal antibody to human DR5, generates apoptosis in a variety of human tumor cell lines and inhibits tumor growth in vivo ( Nature Med 7:954-60, 2001 and Clin Cancer Res 9:3731-41, 2003). (
  • Generation of stable monoclonal antibody-producing B cell receptor-positive human memory B cells by genetic programming. (
  • We show that IL-6 is sufficient and necessary to induce IL-21 production by naive and memory CD4 + T cells upon T cell receptor stimulation. (
  • However, expression of the transgene is not restricted to B cells, leaving open the possibility that other cells may require a functional gp130 receptor. (
  • B cell receptor signaling has been implicated and the strength of the signal may be the determining factor 3 . (
  • For the design of the construct we combined the transmembrane domain of the EGF-receptor with a hemagglutinin epitope and a biotin acceptor peptide and performed a transposon-mediated transfection of myeloma cell lines. (
  • Since LPS is a costimulatory immunogen that can react with both the B-cell receptor (BCR) and the Toll-like receptor 4 (TLR4), these results suggest a mechanism for the selective pressure that leads to clonality of these B-cell clusters and opens the possibility that infection and the attendant exposure to LPS plays a role in the chronic rejection of human kidney transplants. (
  • LPS is an immunogen that can react with both the B-cell receptor (BCR) and the Toll-like receptor 4 (TLR4). (
  • We talked about host cells that are perhaps infected with a virus, displaying pieces of that virus, antigenic pieces of that virus in the context of a surface receptor called MHC-1, presenting that. (
  • This mechanism is similar to that of another anti-psoriasis antibody, brodalumab, which binds to the interleukin-17 receptor. (
  • Antibodies to the F. tularensis lipopolysaccharide (LPS) have been shown to be protective against respiratory tularemia in BALB/c, C3H/HeN, C57BL/6, and C57BL/10 mice, and F. tularensis antibodies, most of which are directed to LPS, have been shown to ameliorate tularemia in humans ( 13 - 22 ). (
  • My review will be focused primarily on mouse B cell development (although there are great similarities with humans), as that has been the primary focus of my work as well as the host for monoclonal antibody development here at MBS. (
  • Why do humans need cells? (
  • Now, Regeneron Pharmaceuticals says its COVID-19 antibody-drug cocktail under development prevented and treated the disease in monkeys and hamsters, showing promise that it may work in humans. (
  • Furthermore, recent advances in antibody engineering techniques together with antibody fragments, display technologies, immunomodulation, and broad applications of antibodies are discussed to enhance innovative antibody production in pursuit of a healthier future for humans. (
  • If you're developing a vaccine, you want to fill up this compartment with cells that respond to your target antigen," says co-senior author F. Eun-Hyung Lee, MD, assistant professor of medicine at Emory University School of Medicine and director of Emory Healthcare's Asthma, Allergy and Immunology program. (
  • Four groups of investigators plan to utilize their collective talents in structural immunology, vaccinology, inflammation research, biomaterials and B cell biology to deliver lipid-embedded MPER nanoparticles for vaccination of animals in order to generate BNABs. (
  • Advanced antibody engineering techniques have extensive applications in the fields of immunology, biotechnology, diagnostics, and therapeutic medicines. (
  • Such substances are known as soluble antibodies and perform important functions in countering infections. (
  • More studies in this area would help us understand how mutations in RAS signaling drive malignancy, and may point to novel targets for antibody and cellular-therapy-based treatment in RAS-driven cancers. (
  • Two herpesviruses often contracted during childhood are Epstein-Barr virus (EBV), which establishes latent infection in the memory B-cell (MBC) compartment ( 1 , 2 ), and Cytomegalovirus (CMV), which has a number of latency targets including CD34 + and CD33 + hematopoietic cells ( 3 , 4 ). (
  • Trinchieri had already shown that the drug Interleukin-12 targets only TH2 cells but leaves the rest of the immune system intact. (
  • This means your immune system mistakenly targets healthy cells and tissues in the body. (
  • The Foundation has awarded Dr. Sainz both for his strong career path and for the strength of his proposal, a promising approach that has the ultimate goal of fighting pancreatic cancer by identifying new therapeutic targets associated with cancer stem cells, which represent between 1 and 5% of the total tumor mass. (
Antibody-secreting cells with a phenotype of Ki-67<sup>low</sup>, CD138<sup>high</sup>, CD31<sup>high</sup>, and CD38<sup>high<...
Antibody-secreting cells with a phenotype of Ki-67<sup>low</sup>, CD138<sup>high</sup>, CD31<sup>high</sup>, and CD38<sup>high<... (
Mac-1-negative B-1b phenotype of natural antibody-producing cells, including those responding to Galα1,3Gal epitopes α1,3...
Mac-1-negative B-1b phenotype of natural antibody-producing cells, including those responding to Galα1,3Gal epitopes α1,3... (
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