T cells play a role in what immunity? Cell-mediated immunity and produce sensitized lymphocytes that secrete cytokines B cells are derived from what precursor? Common lymphoid precursor (CLP) Common lymphoid precursor differentiate into what? B cell progenitor cell Early lymphocyte progenitors can becomes what? T-cell, B-cell NK cells, or dendritic cells What are some example of differentiation of B cell? Pro- B cells Pre-B cells Immature B cells Mature B cells Activated B cells Plasma cells Memory cells The earliest B-cell precursor can be recognized by the presence of a surface molecule called? CD45R What so important about antigen-independent phase? Process that prepares them for role in antibody production and restricts the types of antigen to which the cell can respond. How does influence of growth factors and cytokines effect the differentiation of B cells? This causes rearrangement of genes to occur and codes for the heavy and light chains of an antibody molecule. After the rearrangement of genes occurs what is the outcome? B lymphocyte programmed to produce a unique antibody molecule, consisting of two identical light chains and two identical heavy chains. When B lymphocytes produce two identical light chains and two identical heavy chains, what is this process called? Pro-B cell What are some example of markers that exist on surface of pro-B cells? CD19, CD45R, CD43, CD24, and c-Kit In order for pro-B cells to differentiate into cell successfully what must occur? Successful rearrangement of heavy-chains genes. What cell interact with pro-B cells to secrete cytokines, hormones, chemokines, and adhesion molecules? Stromal cells What does the pre-B stage begins? When synthesis of the chain part of the antibody molecule occurs pre-B cells is complete which marker surface marker does it lose? CD43 marker as well as c-Kit and TdT Where does Mu chains accumulate? In the cytoplasm Which combination of chain forms the pre-B cell receptors? Combination of two heavy chains and two surrogate light chains plus two very short (Ig-α and Ig-β) The pre-B cell receptor adheres to what part of the body? Bone marrow stromal cell membranes and transmits a signal to prevent rearrangement of any heavy-chains genes
What is important in effector functions of immunoglobulin molecules, which include opsonization and complement fixation? FC fragment What are the remaining 2 identical fragments called? Fab fragments (fragment antigen-binding) Because precipitation would not occur if Fab fragments were allowed to react with antigen, what was gu100,essed that each fragment represented? One antigen-binding site and that 2 such fragments were present in an intact antibody molecule What does each Fab fragment consist of? One L chain and one-half of a H chain How is each Fab fragment held together? Disulfide bonding What was to cleave IgG at the side of the interchain disulfide bonds, yielding one single fragment with molecular weight of 100,000 d and all the antigen-binding ability, known as F(ab)2? Proteolytic enzyme pepsin What additional fragment was similar to FC except that it disintegrated into several smaller pieces? FC’ What is found in the urine of patients with multiple myeloma? Bence Jones porteins What type of chains were being secreted by malignant cells in patients with multiple myeloma? L chains Who discovered Bence Jones proteins in 1845? Dr. Henry Bence Jones When heated to 60°C, Bence Jones proteins ____ from urine, but on further heating to 80°C, they ____. precipitated; redissolved What were the two main types of L chains in Bence Jones proteins? Kappa (κ) and lambda (λ) How much amino acid is contained in each L chain? Between 200-220 amino acids What was the region called from positions number 111 and one each type had essentially the same sequence? Constant region What was the amino-terminal end called? Variable region What is the difference between the κ and λ chains? Amino acid substitutions at a few locations along the chain (T or F) Both κ and λ L chains are found in all 5 classes of immunoglobulins, but only one type is present in a given molecule. True What demonstrated the presence of domains similar to those in the L chains- that is, variable and constant regions? H chain sequencing What is the first approximately 110 amino acids at the amino-terminal end? Variable domain
What repeated contact with antigen continually increase? A specific lymphocyte pool What explains the kinetics of the immune response? Clonal selection Who proposed a solution to the tissue of the large number of genes required by the clonal selection theory? Dryer and Bennett What did Dryer and Bennett suggest? The constant and variable portions of immunoglobulin chains are actually coded by separate genes could be a small number coding for the ____ region and a larger number coding for the ____ region. Constant; variable What happens within lymphocytes? Genetic rearrangements What controls synthesis of a particular immunoglobulin, and through a random selection process these individual segments are joined to commit that lymphocyte to making antibody of a single specificity? More than one gene (T or F) B cells are genetically preprogrammed to synthesize very specific antibody. True What antibodies are used for diagnostic testing and for therapeutic purposes? Monoclonal antibodies Why is the normal response to antigen heterogeneous? A purified antigen has multiple epitopes that stimulate a variety of B-cell clones In 1975, what did Georges Kohler and Cesar Milstein discover? A technique to produce antibody arising from a single B cell In Kohler and Milstein’s technique, what is fused with an activated B cell? A myeloma cell What is a myeloma cell? A cancerous plasma cell (T or F) Plasma cells normally produce antibody. True What kind of cell line is chosen for the Kohler and Milstein’s technique? A particular cell line that is not capable of producing antibody What enzyme is deficient in the cell line that is not capable of producing antibody? Hypoxanthine guanine phosphoribosyl transferase (HGPRT) What enzyme is incapable of synthesizing nucleotides from hypoxanthine and thymidine, which are needed for DNA synthesis? Hypoxanthine guanine phosphoribosyl transferase What cells are harvested after a mouse is immunized with a certain antigen? Spleen cells What cells are combined in the presence of polyethylene glycol (PEG), a surfactant? Spleen and myeloma cells What is produced when the PEG brings about fusion of plasma cells with myeloma cells? Hybridoma
immune complexes to the liver and spleen? What is the most efficient cofactor for factor cleavage of C3b? MCP How does MCP also help to control the alternative pathway? Since binding of factor B to C3b is inhibited What is capable of dissociating both classical and alternative pathway C3 convertases? DAF What portion of DAF is covalently attached to a glycophospholipid anchor that is inserted into the outer layer of the membrane lipid bilayer? The carboxy-terminal What is the reason that DAF can C3 convertase sites that are not immediately adjacent to it? arrangement of DAF in the lipid bilayer allows DAF mobility within the membrane What is the reason that the presence of DAF on host cells protects them from bystander lysis and is one of the main mechanisms used in discrimination of self from nonself? because foreign do not possess DAF What is the principal soluble regulator of the alternative pathway? factor H Which factor acts by binding to C3b, thus preventing the binding of factor B? factor H C3b in the fluid phase has a hundredfold greater affinity for which factor than for factor B? factor H On cell surfaces, C3b preferentially binds which factor? Factor B Which factor accelerates the dissociation of the C3bBb complex on cell surfaces? Factor H Which factor acts as a cofactor that allows factor I to break down C3b Factor H Which protein is also known as vitronectin? S protein Which protein interacts with the C5b67 complex as it forms in the fluid phase and prevents it from binding to cell membranes? S protein What causes binding of C8 and C9 to still proceed, but polymerization of C9 does not occur, and the complex is unable to insert itself into the cell membrane or to produce lysis? S protein What also acts to formation of the membrane attack complex besides S protein? Membrane inhibitor of reactive lysis (MIRL), or CD59 What protein’s main function is to bind to C8 and prevent insertion of C9 into host cell membranes? Membrane inhibitor of reactive lysis (MIRL), or CD59 What protein plays an important role as part of the B-cell coreceptor for antigen? CR2
Lysis may be another end result of complement activation, such as in what? cold autoimmune hemolytic anemia What usually manifests itself in increased susceptibility to infection and delayed clearance of immune complexes? Hereditary deficiency of any complement protein Most of these complement protein conditions are inherited on an autosomal recessive gene, and they are quite rare, occurring in what percent of the general population? 0.03% A second deficiency that occurs with some frequency is that of mannose-binding lectin, found in what percent of the population? 3 – 5% Lack of what has been associated with pneumonia, sepsis, and meningococcal disease in infants? MBL The most serious deficiency is of what, because it is the key mediator in all pathways? C3 Individuals with paroxysmal nocturnal hemoglobinuria (PNH) have red cells that are deficient in what? DAF Some studies indicate that a DAF deficiency is associated with a lack of what? CD59 (MIRL) A deficiency in the what of the DAF molecule prevents its insertion into the cell membrane? glycophospholipid anchor What prevents insertion of C9 into the cell membrane by binding to the C5b678 complex, thus inhibiting formation of transmembrane channels? CD59 Recurrent attacks of angioedema that affect the extremities, skin, gastrointestinal tract, and other mucosal surfaces are characteristic of? hereditary angioedema What results in excess cleavage of C4 and C2, keeping the classical pathway going and creating kinin-related proteins that increase vascular permeability? deficiency or lack of What are the methods most frequently used to assay individual complement components? radial immunodiffusion (RID) and nephelometry Assays are available for Clq, C4, C3, C5, factor B, factor H, factor I, C1 inhibitor, and C3a, C4a, and C5a, but what can they not tell about the factors? whether the molecules are functionally active What is most commonly used to measure lysis, the end point of complement activation, as a functional test of complement activity? The hemolytic titration (CH50) assay What test measures the amount of patient serum required to lyse 50 percent of a standardized The hemolytic titration (CH50) assay