Showing papers on "Antibody published in 1976"

Derivation of specific antibody-producing tissue culture and tumor lines by cell fusion

Abstract: Cell fusion techniques have been used to produce hybrids between myeloma cells and antibody-producing cells. The hybrid lines derived are permanently adapted to grow in tissue culture and are capable of inducing antibody-producing tumors in mice. Spleens from mice immunized against sheep red blood cells (SRBC) were fused to an 8-azaguanine-resistant clone (X63-Ag8) of MOPC 21 myeloma. Over 50% of the derived hybrid lines produce and secrete immunoglobulins different from the MOPC 21 myeloma. About 10% of the hybrid lines exhibit anti-SRBC activity. The high proportion of antibody-producing hybrids suggests that the fusion involves a restricted fraction of the spleen cell population, probably cells committed to antibody production. In order to avoid the presence of the MOPC 21 heavy chain in the specific hybrids, another myeloma cell line (NSI/1-Ag4-1) has been used. This is a nonsecreting variant of the MOPC 21 myeloma which does not express heavy chains. Three anti-SRBC (probably of the mu, gamma2b and gamma1 classes, respectively) and two anti-2,4,6-trinitrophenyl (of the mu class) antibody-producing hybrids have been repeatedly cloned. By random selection and by selection of specific clones according to their lytic activity (clone plaque selection), a number of different lines have been constructed. Such lines express different combinations of the four possible chains of each hybrid line: the myeloma gamma and K chains and the specific antibody heavy and light chains. In three cases (Sp1, Sp2 and Sp7) it is shown that only the specific H and L combination has activity and that the myeloma chains are unable to substitute for them. In most cases lines have been derived which no longer express the MOPC 21 chains but only the specific antibody chains.

A plaque assay for all cells secreting ig of a given type or class.

Abstract: A modification of the hemolytic plaque assay using protein A-coated red cells is described which makes use of the fact that the Fc portion of IgG binds to protein A. A number of murine plasmacytomas secreting different classes of Ig have been tested for plaque formation with these indicator red cells. In the presence of complement-binding antibodies specific for the corresponding class of secreted Ig, between 10 and 70 % of all plated myeloma cells formed plaques. The assay shows a prozone effect in excess of antibody, suggesting that complexes of antibody and secreted Ig effect lysis of the target cells. This assay can be used to enumerate cells secreting any molecules for which complement-binding antibodies are available.

Fusion between immunoglobulin-secreting and nonsecreting myeloma cell lines.

Abstract: The defects in two nonsecreting variant clones of the mouse plasmacytoma MOPC 21 (P3) were studied by tissue culture methods. The variants (NSI and NSIII) do not synthesize detectable heavy chains. NSI synthesizes, but does not secrete, light chains and NSIII does not synthesize light chain. A screening procedure was used allowing the detection of revertant cells secreting immunoglobulin. The method is based on a hemolytic plaque assay using anti-immunoglobulin-coated red cells. No revertants were detected among 2 x 10(7) cells. Both variant lines were fused to another myeloma line (PI) which secretes a complete immunoglobulin and excess light chains. Analysis of the products by isoelectric focusing showed that in the hybrids there was no reactivation of synthesis of the nonexpressed chains. The defects leading to loss of synthesis cannot therefore be complemented in the hybrid lines. The secretion of light chain in NSI, on the other hand, could be complemented in the hybrid but the light chain was only secreted as part of a new immunoglobulin hybrid molecule.

The Raji cell radioimmune assay for detecting immune complexes in human sera.

Abstract: A sensitivie and simple procedure for the detection and quantitation of soluble complement (C)- fixing immune complexes in sera of patients with various disease states has been developed by utilizing C receptors on Raji cells. These cells lack membrane-bound immunoglobulin but have receptors for IgG Fc, C3b, C3d, and possibly with other C proteins. Uptake experiments showed that both aggregated human gamma globulin (AHG) and 7S IgG bound to receptors for IgG Fc; however, AHG reacted with C bound to cells only via receptors for C and this binding was much more efficient than via IgG Fc receptors. AHG was used as an in vitro model of human immune complexes and its uptake by Raji cells was quantitated by 125I-radiolabeled antihuman IgG. The limit of sensitivity of this test was 6 mug AHG/ml serum. The ability of Raji cells to detect AHG in serum depended on the amount of radioactive antibody used and the size of aggregates. The presence of an excess of C somewhat inhibited binding of AHG containing C to Raji cells. The efficient binding of AHG by receptors for C on Raji cells was used for the detection and quantitation of immune complexes in human sera. Raji cells were incubated with sera to be tested and then reacted with excess radiolabeled antihuman IgG; the amount of radioactivity bound to the washed cells was determined and referred to a standard curve of radioactive antibody uptake by cells previously incubated with increasing amounts of AHG in serum. Thereby immune complexes were detected and quantitated in serum hepatitis, systemic lupus erythematosus, vasculitis, subacute sclerosing panencephalitis, dengue hemorrhagic fever, and malignancies.

E Antigen and Anti-E in the Serum of Asymptomatic Carrier Mothers as Indicators of Positive and Negative Transmission of Hepatitis B Virus to Their Infants

Abstract: Testing of serum samples of 23 pregnant women who were asymptomatic carriers of hepatitis B surface antigen for e antigen and antibody to e with an immunodiffusion technic identified 10 mothers with e antigen and seven with e antibody. Their babies were tested for hepatitis B surface antigen in serum at intervals for more than 12 months. In all 10 babies born to e-antigen-positive mothers hepatitis B surface antigen developed and persisted through the observation period, and all 10 elder siblings of these newborn babies were found to be asymptomatic carriers. In remarkable contrast, all seven babies born to mothers positive for antibody to e escaped antigenemia, and none of their three elder siblings carried surface antigen. On the basis of these results, e antigen may be used as an indicator of transmission, and antibody to e as that of absence of transmission of hepatitis B virus from carrier mothers to children. (N Engl J Med 294: 746–749, 1976)

Detection of immune complexes in unheated sera by modified 125I-Clq binding test. Effect of heating on the binding of Clq by immune complexes and application of the test to systemic lupus erythematosus.

Abstract: The 125I-Clq binding test was modified in order to allow for the detection of immune complexes in native unheated human serum. Indeed, heat-inactivation (56 degrees, 30 min) was found to reduce the Clq-binding activity of immune complexes mixed with native serum. This effect was not observed when EDTA was added to the native serum before mixing the immune complexes. The modified 125I-Clq binding test was performed in two steps: first, the tested native serum sample was incubated for 30 min at 37 degrees C with 0.13 M EDTA in order to prevent the integration of 125I-Clq into the intrinsic Clqrs complex, second, 125I-Clq and polyethylene glycol (final concentration 2.5%) were added to this mixture, and further incubated for 1 hr at 4 degrees C. Under these conditions, free Clq remained soluble whereas Clq bound to macromolecular complexes was precipitated. The competitive effect of intrinsic Clq and the interference of other substances such as DNA or bacterial LPS were very limited. The modified Clq binding test was applied to the clinical investigation of 44 patients with systemic lupus erythematosus; and increased Clq binding activity (Clq-BA) was observed in 91% of the samples. The level of Clq-BA was found to be significantly correlated to the DNA-binding capacity and to the decrease of the level of some complement components.

Correlation of Maternal Antibody Deficiency with Susceptibility to Neonatal Group B Streptococcal Infection

Abstract: We investigated the role of maternal antibody in neonatal Group B streptococcal infection with a radioactive antigen-binding assay employing a purified polysaccharide antigen with both Type III and Group B determinants. Serums from seven women who gave birth to infants who had invasive Group B streptococcal infection with Type III strains were all deficient in antibody. In contrast, serums from 22 of 29 pregnant Type III vaginal carriers whose infants were healthy contained antibody with a prevalence significantly different from that in women delivering infants with Type III disease (P < 0.01). Three healthy neonates born to women with antibody in serums had demonstrable antibody in umbilical-cord serum. These data suggest that transplacental transfer of maternal antibody protects infants from invasive Group B streptococcal infection with Type III strains. (N Engl J Med 294:753–756, 1976)

Immunochemical evidence of cholecystokinin-like peptides in brain

Abstract: A NUMBER of peptides including substance P1,2 somatostatin3 and vasoactive intestinal peptide4, have been found both in nerve cells of the brain and gut and in gastrointestinal endocrine-like cells. The biological significance of the occurrence of the same peptides in endocrine and nerve cells is not yet clear, although Pearse has suggested that these cell types might share a common embryological (neuroectodermal) origin5. An antibody to the antral hormone gasrin has recently been shown to cross react with material in extracts of the central nervous system (particularly cerebral hemispheres) of a number of vertebrate species including dog and man6. It is known that in antral mucosa, and in blood, gastrin occurs in several different forms of which the most important are peptides of 17 (G17) and 34 (G34) amino acid residues7. The C-terminal hepta-decapeptide of G34 is identical with G17, and G34 may well be a biosynthetic precursor of G17 (ref. 7). The C-terminal pentapeptide of the two gastrins is also identical with that of the intestinal hormone cholecystokinin (CCK)8, and antibodies specific for the C terminus of gastrin frequently cross react with CCK9. The present study was undertaken to clarify the relationships between the gastrin-like activity in brain and the characteristic forms of gastrin and CCK. We found the distribution of the brain components on Sephadex G-25 to differ from those of previously characterised forms of gastrin and CCK. The pattern of reactivity with different antisera suggests, however, that the brain factors resembled CCK-like peptides more closely than gastrin-like peptides.

Fluorescent antibody localization of myosin in the cytoplasm, cleavage furrow, and mitotic spindle of human cells.

Abstract: We have studied the distribution of myosin molecules in human cells using myosin-specific antibody coupled with fluorescent dyes. Rabbits were immunized with platelet myosin or myosin rod. They produced antisera which precipitated only myosin among all the components in crude platelet extracts. From these antisera we isolated immunoglobulin-G (IgG) and conjugated it with tetramethylrhodamine or fluorescein. We separated IgG with 2-5 fluorochromes per molecule from both under- and over-conjugated IgG by ion exchange chromatography and used it to stain acetone-treated cells. The following controls established the specificity of the staining patterns: (a) staining with labeled preimmune IgG; (b) staining with labeled immune IgG adsorbed with purified myosin; (c) staining with labeled immune IgG mixed with either unlabeled preimmune or immune serum; and (d) staining with labeled antibody purified by affinity chromatography. In blood smears, only the cytoplasm of platelets and leukocytes stained. In spread Enson and HeLa cells, stress fibers stained strongly in closely spaced 0.5 mum spots. The cytoplasm stained uniformly in those cells presumed to be motile before acetone treatment. In dividing HeLa cells there was a high concentration of myosin-specific staining in the vicinity of the contractole ring and in the mitotic spindle, especially the region between the chromosomes and the poles. We detected no staining of erythrocytes, or nuclei of leukocytes and cultured cells, or the surface of platelets and cultured cells.

The late phase of the immediate wheal and flare skin reaction. Its dependence upon IgE antibodies.

Abstract: IgE antibodies are usually thought to induce only immediate skin reactions. We have shown that the intradermal injection of a number of different allergens can produce a prolonged inflammatory reaction after the immediate wheal and flare in most sensitive subjects. This late inflammatory response occurs 6-12 h after challenge and is characterized by diffuse edema, erythema, pruritus, and heat. Both immediate and late responses can also be seen after passive sensitization of skin sites in nonatopic subjects. That IgE is involved in inducing the reaction was shown by the abolition of both immediate and late responses by passive transfer tests in the following experiments: (a) heating atopic serum at 56degreesC for 4 h, (b) removing IgE from the atopic serum by a solid phase anti-IgE immunoabsorbent, and (c) competitively inhibiting the binding of IgE antibodies to cells by an IgE myeloma protein. In addition, both responses were induced by affinity chromatography-purified IgE antibody, followed by antigenic challenge. Very similar lesions could also be induced by intradermal injection of Compound 48/80, thus suggesting a central role in the reaction for the mast cell or basophil. Histologically, the late phase is characterized by edema and a mixed cellular infiltration, predominantly lymphocytic but also containing eosinophils, neutrophils and basophils. Direct immunofluorescent staining did not show deposition of immunoglobulins or complement components, except IgM in 2 of 15 and C3 in 1 of 15 patients. This finding indicates that the late phase does not depend on the deposition of immune complexes. The results of the study suggest that IgE-allergen interaction on the surfaces of mast cells or on infiltrating basophils causes both immediate and late cutaneous responses.

Effect of Human Leukocyte Interferon on Hepatitis B Virus Infection in Patients with Chronic Active Hepatitis

Abstract: Four patients with chronic hepatitis B infection and chronic active hepatitis were treated with human leukocyte interferon. Three of them had consistently elevated levels of circulating Dane-particle markers, including Dane-particle-associated DNA polymerase activity, hepatitis B core antigen and Dane-particle-associated DNA. Parenteral interferon administration at a dosage between 6.0 X 10(3) and 17 X 10(4) U per kilogram per day was associated with a rapid and reproducible fall in all Dane-particle markers in the three patients. The suppressive effect was transient when the interferon was given for 10 days or less but appeared to be more permanent when administration was prolonged for a month or more. In addition, long-term interferon therapy was associated with a marked fall in hepatitis B surface antigen in two of three patients and a disappearance of e antigen in two of two patients. Interferon may be useful in limiting carrier infectivity or eradicating chronic infection.

Isoniazid liver injury: clinical spectrum, pathology, and probable pathogenesis

Abstract: The clinical spectrum of isoniazid-induced liver injury seems to be clinically, biochemically, and histologically indistinguishable from viral hepatitis, except that the injury occurs primarily in persons older than 35 years. A possible relation between susceptibility of patients to isoniazid liver injury and rapid metabolism (acetylation) of the drug has been found. Examination of isoniazid metabolites showed that patients with rapid acetylator phenotype hydrolyze much more isoniazid to isonicotinic acid and the free hydrazine moiety than do slow acetylators. The hydrazine moiety liberated from isoniazid is primarily acetylhydrazine, and studies in animals show this metabolite to be converted to a potent acylating agent that produces liver necrosis. It seems likely that formation of chemically reactive metabolites is also the biochemical event initiating isoniazid liver injury in man. Recognition of the seriousness of isoniazid hepatic injury, not readily accepted at first, has led to revisions in the uses of isoniazid prophylaxis.

Cell membrane antigen isolation with the staphylococcal protein A-antibody adsorbent.

Abstract: Procedures are detailed for the rapid isolation of representative cell membrane antigens with protein A-bearing staphylococci as an adsorbent for IgG antibodies complexed with the antigens. Cell surface membrane proteins were radioiodinated and solubilized in nonionic detergent. Specific antisera were subsequently added and the immune complexes precipitated by addition of the staphylococcal adsorbent and low speed centrifugation. The antigens isolated included surface immunoglobulins from mouse and human lymphocytes, human beta-microglobulin and HL-A alloantigens, mouse H-2 alloantigens, and the murine leukemia virus glycoprotein gp 70. Rabbit, sheep, goat, and mouse antisera were all effective for the specific phase of the precipitation reaction. The surface membrane immunoglobulins of mouse splenic lymphocytes and human peripheral blood lymphocytes differed with respect to class composition and protein A reactivity. Mouse lymphocyte surface immunoglobulins were nonreactive with protein A, whereas a high proportion of human lymphocyte surface immunoglobulins of different classes bound directly to the staphylococci. In sequential immunoprecipitation studies the prior isolation of one antigen had no appreciable effect on the subsequent recovery of another antigen. Adsorption of antigen-antibody complexes is quantitative when protein A sites are provided in excess over antiserum IgG sites, and this obviates the need for equivalence point titrations for optimal precipitation necessary with alternative double antibody techniques.

The Sézary syndrome: a malignant proliferation of helper T cells.

Abstract: The Sezary syndrome is a frequently lethal disease characterized by circulating malignant cells of thymus-derived (T)-cell origin. The capacity of circulating malignant lymphocytes from patients with this syndrome to synthesize immunoglobulins and to function as helper or suppressor cells regulating immunoglobulin synthesis by bone marrow-derived (B) lymphocytes was determined. Peripheral blood lymphocytes from normal individuals had geometric mean immunoglobulin synthetic rates of 4,910 ng for IgM, 1,270 ng for IgA, and 1,625 ng for IgG per 2 X 10(6) cells in culture with pokeweed mitogen for 7 days. Purified normal B cells had geometric mean synthetic rates of 198 ng for IgM, 145 ng for IgA, and 102 ng for IgG. Leukemic cells from patients with the Sezary syndrome produced essentially no immunoglobulins. Adding normal T cells to normal B cells restored their immunoglobin producing capacity. Leukemic cells from four of five patients tested had a similar capacity to help immunoglobulin synthesis by purified normal B cells. Additionally, Sezary cells from one patient studied induced a nearly 10-fold increase in IgA synthesis by lymphocytes from a child with ataxia telangiectasia and selective IgA deficiency. Furthermore, these Sezary cells induced more than a 500-fold increase in IgG and IgA synthesis by lymphocytes from a child with Nezelof's syndrome. When Sezary cells were added to normal unfractionated lymphocytes, they did not suppress immunoglobulin biosynthesis. In addition, unlike the situation observed when large numbers of normal T cells were added to purified B cells, there was no depression of immunoglobulin synthesis at very high malignant T-cell to B-cell ratios. These data support the view that Sezary T cells do not express suppressor cell activity. The results presented in this paper suggest that neoplastic lymphocytes from the majority of patients with the Sezary syndrome originate from a subset of T cells programmed exclusively for helper-like interactions with B cells in their production of immunoglobulin molecules.

Early production of intracellular IgM by B-lymphocyte precursors in mouse.

Abstract: IN BALB/c mice, surface immunoglobulin (Ig)-bearing B lymphocytes are first detectable by immunofluorescence at 17 d gestation in the liver and spleen1. Explants of 14-d foetal liver1 and spleen2, and 15-d bone marrow (our unpublished observations), have been shown to generate Ig-bearing B cells in vitro after 4–7 d of culture, suggesting that B lymphocytes normally develop multifocally in the haemopoietic tissues of mice. We have used direct immunofluorescence to demonstrate cells with intracellular IgM and no detectable surface Ig in mouse foetal liver as early as 12 d gestation. Our results suggest that B lymphocyte precursors synthesise IgM several days before they incorporate these molecules into their plasma membranes as cell-surface receptors for antigen.

Cell surface antigens of human malignant melanoma: mixed hemadsorption assays for humoral immunity to cultured autologous melanoma cells.

Abstract: We studied how frequently patients with malignant melanoma have specific antibody to cell surface antigens of cultured autologous melanoma cells as demonstrated by mixed hemadsorption assays. Of 35 patients studied over periods ranging from 1 to 36 months with Stage II, III, and IV disease, two showed consistent and high titered reactivity against autologous melanoma cells, two showed less consistent and intermediate reactivity, seven showed sporatic, low titered reactivity, and the remainder were consistently negative. A detailed analysis was carried out with the sera of one patient with sufficiently high titer against autologous melanoma cells. By direct tests and by absorption analysis with a variety of melanoma and nonmelanoma cell lines which included autologous fibroblasts, the antigen could not be demonstrated on any cell type other than the autologous melanoma.

Association of antibodies to ribonucleoprotein and Sm antigens with mixed connective-tissue disease, systematic lupus erythematosus and other rheumatic diseases.

Abstract: Extractable nuclear antigen contains ribo-nuclease-sensitive (ribonucleoprotein) and ribonuclease-resistant (Sm) components. To determine the diagnostic usefulness of antibodies to these antigens, a multicenter study was undertaken in which serums were analyzed for these antibodies and the findings compared with clinical and other laboratory characteristics of the patients. Of 100 patients with hemagglutinating antibodies to ribonuclease-sensitive extractable nuclear antigen, and only the same antibodies by immunodiffusion, 74 per cent had typical features of mixed connective-tissue disease; 12 features of systemic lupus erythematosus, eight those of scleroderma and six an undifferentiated mild connective-tissue disease. Of 27 patients with hemagglutinating antibodies to ribonuclease-resistant extractable nuclear antigen (and Sm antibodies by immunodiffusion), 85 per cent had typical systemic lupus. Thus, antibodies to nuclear ribonucleoprotein and Sm are of diagnostic use; if the serum contains only ribonucleoprotein antibody in high titer, it is likely that the patient has mixed connective-tissue disease.

Subpopulations of Human T Cells Identified by Receptors for Immunoglobulins and Mitogen Responsiveness

Abstract: Human T lymphocytes in peripheral blood have been shown to have receptors for IgG (Tgamma) or IgM (Tmu). Cultured Tgamma cells do not express receptors for IgM and purified Tmu cells do not have receptors for IgG, thus they appear to be distinct T cell populations. Although the two subpopulations show similar response patterns to concanavalin A, Tmu and Tgamma cells exhibit different dose-response curves to phytohemagglutinin. The normal response pattern to phytohemagglutinin requires a mixture of T cell subpopulations suggesting that synergistic interactions may occur.

Type B hepatitis: the infectivity of blood positive for e antigen and DNA polymerase after accidental needlestick exposure

Abstract: To determine the relation between the presence of donor DNA polymerase and e antigen, and recipient hepatitis, we tested, under code, serums from a controlled trial of hepatitis B immune globulin used to treat individuals accidentally inoculated with HBs Ag-positive blood. All recipients lacked antibody to HBs Ag. In 29 of 31 donors, both polymerase and e were in perfect agreement; both demonstrated a highly significant correlation with recipient hepatitis (P less than 0.001). DNA polymerase/e-negative blood did not cause hepatitis. Blood containing polymerase or e antigen did not cause hepatitis in six of 31 and four of 18 recipients, respectively. Hepatitis did not correlate with transaminase or duration of antigenemia in the donor. Polymerase and e appear to be indicators of the relative infectivity of HBs Ag-positive serum, particularly after small-volume exposure. They may be important determinants in assessing infectivity of chronic carriers of HBs Ag and in evaluating efficacy of hepatitis B immune globulin and hepatitis B vaccines.

Membrane and Cytoplasmic Changes in B Lymphocytes Induced by Ligand-Surface Immunoglobulin Interaction

Abstract: Publisher Summary This chapter discusses membrane and cytoplasmic changes in B lymphocytes induced by ligand–surface immunoglobulin (Ig) interaction. Surface Ig is the receptor for antigen molecules on B lymphocytes. Surface Ig has been identified on the B-cell surface by using immunocytochemistry or direct biochemical analysis. The number of Ig molecules presumably serving as antigen receptors on the B cell surface is on the average of 105 molecules per B cell. The amount of surface-bound Ig is large comparing to the number of hormone receptors needed to trigger certain cellular responses. One could speculate that many of the surface Ig–antigen interactions result in nonfunctional events; therefore, many receptors are needed. The B cell requires such a high number of receptors to effectively bind antigen molecules of large size and variable epitope densities or a number of successive hits are needed in these cells to reach an effective threshold of stimulation. The distribution of surface Ig and other surface macromolecules has been studied at the ultrastructural level by using various methods. One method was the ultrastructural analysis of regular thin section of cells exposed to antibodies conjugated to a large visible molecule.

Routine assay for the detection of immune complexes of known immunoglobulin class using solid phase C1q.

Abstract: A new, sensitive and quantitative technique for the routine estimation of immune complexes has been devised. The assay involved the binding of immune complexes to Clq linked to the surface of plastic tubes; the amount of immune complex bound is then determined by adding radiolabelled anti-human IgG. Immune complexes were detected in twelve out of thirty-one patients with systemic lupus erythematosus. The test should prove useful in the diagnosis of immune complex diseases and will be valuable in the evaluation of disease activity.

A new I subregion (I-J) marked by a locus (Ia-4) controlling surface determinants on suppressor T lymphocytes.

Abstract: In an accompanying publication we show that a subpopulation of T lymphocytes, which includes allotype suppressor T cells, selectively expresses I-region determinants. In this report, we show that these determinants are controlled by a new locus, Ia-4. Unlike the classically defined Ia antigens, they are not found on B lymphocytes. Antibody against Ia-4 determinants cannot be detected by conventional dye exclusion cytoxicity assays, suggesting that they are present on a small subpopulation (less than 10%) of peripheral T lymphocytes. The Ia-4 locus marks a new I subregion, provisionally designated I-J. This chromosomal segment is defined by the crossover positions in strains B10.A(5R) (K-end boundary) and B10.HTT (D-end boundary), and maps between the I-B and I-C subregions.

Studies on the mechanism of phagocytosis. II. The interaction of macrophages with anti-immunoglobulin IgG-coated bone marrow-derived lymphocytes.

Abstract: We have examined the effect of the distribution of anti-immunoglobulin IgG molecules on the surface of bone marrow-derived lymphocytes upon the interaction of these cells with macrophages. Lymphocytes which were diffusely coated with antibodies to surface immunoglogulin were ingested by macrophages. Lymphocytes which had the same number of anti-immunoglobulin IgG molecules redistributed to one pole of the surface bound to the macrophages' Fc receptors but were not ingested. These results confirm our previous hypothesis that ingestion of an immunologically coated particle requires the sequential, circumferential binding of specific receptors on the plasma membrane of a phagocytic cell to immunologic ligands distributed over the entire particle surface. Macrophages which had bound capped lymphocytes by the macrophages' Fc receptors removed the immune complex caps from the lymphocyte surface without destroying the lymphocytes. These lymphocytes remained attached to the macrophage surface. The finding that macrophages can phagocytize immune complexes from the surface of a cell without destroying the cell to which these complexes are attached may be important in understanding the effects of antigens and antibodies on cells participating in a humoral immune response, in identifying the mechanisms by which chronic viral infections are established, and in defining the roles of blocking antibodies in tumor immunity.

Lymphocyte Receptors for Immunoglobulin

Abstract: Publisher Summary This chapter discusses lymphocyte receptors for immunoglobulin (Ig) The methods used to detect lymphocyte receptors for Ig vary widely both as the type of complex utilized and the technique for measuring binding The chapter describes various techniques available The nature of the lymphocytes that bind complexed Ig are considered with reference to the sensitivity and/or specificity of the various methods A detailed consideration of lymphoid cell subpopulations, including the criteria for defining B lymphocytes, T lymphocytes, and undefined lymphocyte-like (UL) cells, is presented in the chapter Any useful Fc receptor assay system should meet certain basic criteria: (1) the percentage of lymphocytes binding Ig should be titratable to a plateau value This assumes a discontinuous distribution of receptors on different subpopulations (2) The Fc dependence of binding should be demonstrated Because the binding of Ig is dependent on the Fc portion of the molecule, this will help ensure that different assays are detecting similar receptors (3) Cells, other than lymphocytes, that bear Fc receptors should be either identified and excluded from counts or removed from the population being tested Such cells include monocytes, macrophages, neutrophils, and basophils

Role of interferon in the pathogenesis of virus diseases in mice as demonstrated by the use of anti-interferon serum. I. Rapid evolution of encephalomyocarditis virus infection.

Abstract: The role of interferon in the pathogenesis of encephalomyocarditis (EMC) virus infection was determined by treating mice with potent, partially purified sheep anti-mouse interferon globulin. In control mice, EMC virus was present in low titers in various visceral organs but attained high titers in the brain towards the 4th to 5th day, at which time mice died with signs of central nervous system disease. In mice treated with anti-mouse interferon globulin, virus was present in high titer in visceral organs 24--36 h after viral inoculation and virtually all mice were dead by 45 h. This rapid evolution of EMC virus infection was not observed in mice treated with the globulin fraction prepared from a normal sheep, from a sheep exhibiting a low anti-mouse interferon-neutralizing titer, nor from a sheep having a high titer of antibody to human leukocyte interferon. The experimental results indicated that anti-interferon globulin neutralized the interferon liberated by virus-infected cells, thus permitting extensive virus multiplication in several visceral organs. We conclude that interferon is an important early component of host resistance to this virus infection.

Biology of Feline Leukemia Virus in the Natural Environment

Abstract: The feline leukemia virus (FeLV) was discovered in 1964 in a cluster of cats with lymphosarcoma The observed clustering of cases of feline lymphosarcoma suggested that FeLV was an infectious agent for cats The development of a simple immunofluorescent test for FeLV permitted a seroepidemiological study to be undertaken on the distribution of the virus in cats living in their natural environment Over 2000 cats were tested, and the results showed conclusively that FeLV is an infectious agent for cats This finding has now been independently confirmed using three different test procedures After the infectious nature of FeLV was discovered, a simple FeLV test and removal program was devised to control the spread of the virus in the natural environment The spread of FeLV was controlled in 45 households by removing the FeLV-infected cats, while in 25 households, where the infected cats were left in contact with the uninfected cats, 12% of the uninfected cats became infected The ultimate control of FeLV awaits the development of an effective FeLV vaccine, which now seems feasible since we have already experimentally immunized some cats with attenuated FeLV Although FeLV is infectious for cats there is no evidence that FeLV can infect humans

Suppressor thymus-derived lymphocytes in fungal infection.

Abstract: Thymus-derived lymphocyte (T-cell) function, as determined in vivo by cutaneous reactivity to several antigens and in vitro by responsiveness to mitogens and antigens, was assessed in 14 patients infected with a variety of fungal organisms. While all patients manifested a normal frequency of peripheral blood T cells, only seven patients reacted to at least one of the antigens used for cutaneous testing and demonstrated normal in vitro T proliferative responses. Three patients exhibited cutaneous anergy but normal in vitro T-cell reactivity while four patients demonstrated persistent anergy and marked in vitro T-cell hyporeactivity which was independent of activity of infection, concurrent medication, or any associated disorders. The marked diminution of in vitro T-cell reactivity noted for these later four patients was not due to a deletion of antigen- or mitogen-reactive cells. Thus, patients' cells which had been initially cultured for 7 days without any mitogenic or antigenic stimulus and which were subsequently washed and recultured with phytohemagglutinin, concanavalin A, or histoplasmin demonstrated a marked increase in their responsiveness. Moreover, this reactivity noted for recultured cells could be suppressed by a nonphagocytic, nonadherent, nonimmunoglobulin-bearing, sheep red blood cell rosette-forming population of cells isolated from the fresh peripheral blood mononuclear cells of the same patient. While these "regulator" T cells were capable of suppressing T-proliferative responses to antigens and mitogens, they did not diminish pokeweed mitogen-induced immunoglobulin synthesis by normal bone marrow-derived lymphocytes. Patients in whom suppressor "T" cells were found were at risk for relapsing, disseminated fungal infection.