Showing papers on "Antigen published in 1974"

Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system.

Abstract: RECENT experiments1–3 indicate that cooperation between thymus derived lymphocytes (T cells) and antibody-forming cell precursors (B cells) is restricted by the H-2 gene complex Helper activity in vivo operates only when T cells and B cells share at least one set of H-2 antigenic specificities Evidence is presented here that the interaction of cytotoxic T cells with other somatic cells budding4–5 lymphocytic choriomeningitis (LCM) virus is similarly restricted

Cell-Mediated Cytotoxicity, Allograft Rejection, and Tumor Immunity

Abstract: Publisher Summary The term “cell-mediated cytotoxicity” applies to lytic reactions that require the participation of lymphoid or non-lymphoid cells but not of added complement. It has been clearly established that several pathways, including different cell types, are involved in cytotoxic reactions in vitro. With membrane-associated antigens, such as transplantation, and tumor-associated antigens, the cytotoxic effect of effector cells on adequate target cells is most often highly specific and requires intimate contact rather than release of diffusible toxic factors. Specific cell-mediated cytotoxicity in vitro can be divided into three categories according to the nature of the effector cells.

Immunological surveillance against altered self components by sensitised T lymphocytes in lymphocytic choriomeningitis.

Abstract: THE cytotoxic activity1,2 of immune thymus-derived lymphocytes (T cells) for 51Cr-labelled fibroblasts, or macrophages infected with lymphocytic choriomeningitis (LCM) virus is restricted by the H-2 gene complex3,4. Specific lysis of LCM-infected monolayer cultures occurs only when targets and overlaying, sensitised T cells share at least one set of H-2 antigenic specificities.

Clonal cell lines from the rat central nervous system

Abstract: Five neuronal and a large collection of putative glial cell lines from the rat central nervous system have been established in clonal cell culture and partially characterised. These cells shed new light on the distribution of neurotransmitter synthesis and brain-specific antigens among nerve and glia.

Lymphocyte-Mediated Cytotoxicity And Blocking Serum Activity To Tumor Antigens

Abstract: Publisher Summary This chapter reviews the evidence for cell-mediated immune reactions against tumors in animals and man, particularly, the reactions that can lead to destruction of neoplastic cells cultivated in vitro. Various mechanisms by which tumor cells can escape from immunological destruction have been discussed, most notably one involving blocking factors, present in the serum. Findings analogous to those obtained when studying tumor immunity (coexistence of cell-mediated reactivity and blocking serum activity) have been summarized from three other areas (pregnancy, allografting, and chimeras). The studies reviewed in the chapter have given a relatively large amount of evidence for various cell-mediated and humoral immunological reactions against growing tumors, and at least some of the reactions observed in vitro appear to be able to influence tumor growth in vivo .

Circulating Immune Complexes in the Serum in Systemic Lupus Erythematosus and in Carriers of Hepatitis B Antigen QUANTITATION BY BINDING TO RADIOLABELED Clq

Abstract: A sensitive and reproducible procedure for the detection of soluble immune complexes in sera from patients with various immunopathological disorders is reported. Radiolabeled C1q is reacted with sera containing immune complexes. Separation of free from complex bound [(125)I]C1q is achieved by selective precipitation with polyethylene glycol (PEG). The method is based on both the large molecular size and the C1q-binding property characterizing immune complexes. The minimal amount of aggregated immunoglobulins thus detected is about 10 mug and that of soluble human IgG-anti-IgG complexes is about 3 mug of complexed antibody. Some immune complexes formed in large antigen excess (Ag(2)Ab) can still be detected by this radiolabeled C1q binding assay. The specificity of the radiolabeled C1q binding test was documented by the inability of antigen-F(ab')(2) antibody complexes to lead to a precipitation of [(125)I]C1q in PEG. In a second step, this radiolabeled C1q binding assay was applied to an experimental model of immune complex disease and was shown to be efficient for the detection of in vivo formed immune complexes.Finally, the technique could be applied to the study of sera from patients with systemic lupus erythematosus (SLE) or to carriers of the hepatitis B antigen (HB-Ag). Significantly increased [(125)I]-C1q binding values were observed in 52 sera from SLE patients when compared to values obtained with healthy blood donors (P<0.001). Particularly high values were seen in active disease, a finding which was confirmed by follow-up studies performed with four SLE patients. No increased [(125)I]C1q binding was seen in 18 healthy carriers of the HB-Ag; whereas, sera from carriers with hepatitis appear to precipitate increased [(125)I]C1q percentages: 7/24 cases with acute transient and 4/7 cases with chronic persistent hepatitis were found to increasingly bind [(125)I]C1q. The results were also used for a correlative study of [(125)I]C1q binding to IgG levels in the sera but increased [(125)I]C1q binding could not be attributed to high serum IgG levels which are likely to account for gammaglobulin aggregates. These examples suggest the utility of the radiolabeled C1q binding assay for the evaluation of immune complex diseases in human pathology.

The gut-associated lymphoid system: nature and properties of the large dividing cells

Abstract: The nature of the lymphoid cells and blasts (i.e. cells labeled in vitro with [3H]-thymidine) of the Peyer's patches (PP), mesenteric lymph nodes (MLN) and thoracic duct lymph (TDL) has been studied by combined immunofluorescence and radioautography, using antisera directed against T (MSLA) or B (MBLA) cell antigenic determinants, or against various Ig chains. The migration pattern of these various cell populations after transfer to syngeneic mice or rats was determined by radioactivity counting and radioautography and the nature of the homed cells was studied by combined immunofluorescence and radioautography. B and T blasts from MLN and TDL have, in contrast to blasts from the peripheral lymph nodes, a marked tendancy to home in the gut, and migrate as well in a graft of fetal intestine as in the recipient's own gut, indicating that this selective accumulation is not the result of a mechanism recognizing antigen absorbed from the gut lumen. The gut-homing B blasts are cells bearing surface IgA (sIgA) and containing intracellular IgA, which transform into IgA plasam cells in the lamina propria. Evidence is discussed that the progenitors of the intestinal IgA plasma cells are proliferating sIgA cells from the PP geerminal centers, which migrate via lymphatics to MLN and TDL and mature during this migration, acquiring intracellular IgA chains as well as a gut-homing mechanism which might be related to this increased IgA synthesis. The gut-homing T blasts migrate both in the lamina propria and the intestinal epithelium. Most, if not all, the intraepithelial lymphocytes of the gut mucosa appear to be T lymphocytes derived from rapidly dividing cells. Evidence is presented for the existence in the lymphoid system of two types of T blasts, one that is circulating and has a marked tendancy to home to the gut, and a second that does not home to the gut and may be sessile.

Role of complement in induction of antibody production in vivo : effect of cobra factor and other c3-reactive agents on thymus-dependent and thymus-independent antibody responses

Abstract: In an in vivo study in mice, suppression by the C3-cleaving protein of cobra venom (CoF), and other C3-reactive agents (zymosan, aggregated IgG, anti-C3 antibodies, and type III pneumococcal polysaccharide) of the thymus-dependent antibody responses to sheep erythrocytes, ovalbumin, and human IgG was demonstrated. The thymus-independent antibody response to polyvinyl-pyrrolidone was however unaffected by CoF. These and other published observations suggest that there may be a requirement for functional C3 in induction of thymus-dependent but not thymus-independent antibody production. A model for the role of C3 in lymphocyte cooperation is proposed based on these data analyzed in the light of existing knowledge of this process. It is postulated that fixed C3 interacting with macrophage See PDF for Structure and B-cell C3 receptors might enhance or facilitate T-dependent presentation of antigen to B cells.

Comparison of Three Agents of Acute Infectious Nonbacterial Gastroenteritis by Cross-Challenge in Volunteers

Abstract: duced in volunteers with bacteria-free stool filtrates derived from each outbreak. These filtrates containing the Hawaii and Montgomery County agents, as well as filtrates containing the previously described Norwalk agent, produced clinically similar illness in volunteers. Therefore, volunteers were cross-challenged to determine whether illness was produced by antigenically related or unrelated agents. It was suggested that the Norwalk and Hawaii agents were antigenically dissimilar, since disease produced by either agent failed to confer immunity to subsequent disease caused by the other. In contrast, similar studies suggested antigenic relatedness between the Norwalk and Montgomery County agents, since Norwalkinduced disease seemed to confer immunity to later challenge with the Montgomery County agent.

Evidence of suppressor cell activity in spleens of mice bearing primary tumors induced by moloney sarcoma virus

Abstract: Spleens from Moloney sarcoma virus (MSV) tumor-bearing C57BL/6N mice contained four times the normal number of mononuclear cells and displayed a markedly elevated "spontaneous" (mitogen-independent) DNA synthesis on a per cell basis. The number of macrophages were increased three-fold while there was a slight reduction in the percentage of T lymphocytes. The phytohemagglutinin (PHA) response on a per cell basis of spleens from tumor-bearing mice was decreased about 90% when compared with normal control mice. The primary in vitro immune response to sheep red blood cells was also suppressed to levels of less than 10% of normals. The PHA response could be restored by purification of MSV spleen cells by rayon adherence columns and by removal of phagocytic cells by an iron/magnet technique. The activity of suppressor cells in MSV spleens was demonstrated in mixtures with syngeneic normal spleen cells where a marked impairment of the PHA response was observed. Spleen cells from tumor-free nude mice and normal spleen cells treated by anti-theta serum plus guinea pig complement (C'), both totally unreactive to PHA, had no such effect. The inhibitor cell in MSV spleens was shown to be insensitive to inactivation by anti-theta plus C', but could be removed by the adherence columns and the iron/magnet technique. These data suggest that this suppressor cell is a cell of the monocyte/macrophage series. Suggestive evidence was also presented that the suppressor cells belong to a proliferating population in MSV spleens. Similar suppressor cells have been previously demonstrated in spleens of mice during a variety of immune responses. Our data show, that a tumor, although stimulating the immune system, nevertheless may be suppressive on certain immune functions through the activation of suppressor cells.

Continuous Lymphoid Cell Lines with Characteristics of B Cells (Bone-Marrow-Derived), Lacking the Epstein-Barr Virus Genome and Derived from Three Human Lymphomas

Abstract: Three exceptional cell lines have been tested for the presence of the Epstein-Barr virus genome by nucleic acid hybridization (complementary RNA·DNA) and Epstein-Barr virus-determined nuclear antigen tests. Two lines were derived from Swedish lymphoma cases and one from an African Burkitt-like lymphoma biopsy that was negative for Epstein-Barr virus DNA and the virus-determined nuclear antigen. All three lines apparently lacked the viral genome. Two of the three lines clearly had characteristics of B-cells (bone-marrow-derived).

Potentiation of t-cell-mediated immunity by selective suppression of antibody formation with cyclophosphamide

Abstract: Delayed-type hypersensitivity (DTH) appears in mice immunized with less than an optimal immunogenic dose of sheep red blood cells (SRBC), but is blocked progressively as antibody production increases in response to larger doses of SRBC. Treatment with cyclophosphamide (CY) was shown to release T cells from this inhibitory influence of the humoral response, and cause enhancement of DTH. The magnitude of this enhancing effect on T-cell activity was markedly dependent on the time of treatment relative to the time of immunization, and on the time chosen for measuring DTH. The reasons for these pronounced effects of timing are threefold: ( a ) CY given before antigenic stimulation has a long-lasting effect on antibody formation, but no apparent effect on the precursors of activated T cells. ( b ) After antigenic stimulation, T cells also become susceptible to CY. ( c ) The production of a nonspecific participant (monocyte) in the DTH reaction is also suppressed by CY, though the supply of circulating monocytes is not immediately affected by the drug. The differential effect of CY on T and B lymphocytes depends on the differing physiological states of the majority of cells that make up these two populations. The former are resting cells that are insensitive to CY until exposed to specific antigen, while the latter are drawn from a rapidly replicating precursor pool and are susceptible to CY at all times.

Heterogeneity of RNA protein antigens reactive with sera of patients with systemic lupus erythematosus. Description of a cytoplasmic nonribosomal antigen.

Abstract: A soluble cytoplasmic RNA protein antigen (La) is described, which precipitates with sera of patients with systemic lupus erythematosus and a small number of patients who lack antinuclear factors but who have various connective tissue symptoms. Antibodies to the cytoplasmic RNA protein are almost invariably (8 of 9 cases) accompanied by antibodies to a non-nucleic acid cytoplasmic antigen, Ro. Description of this antigen enlarges the spectrum of nucleic acid antigens reactive with the sera of patients with systemic lupus erythematosus.

Cell-Mediated Immunity to Tumor Cells

Abstract: Publisher Summary An individual's immunological response to some of the antigens can result in protection against tumor growth. However, it has been found that the generation of antitumor immunity is not always effective and may at times even lead to the acceleration of tumor growth. This chapter reviews the information on the role of the immune system in limiting tumor growth and discusses the concept of immunological surveillance. It discusses the types of antigens that have been associated with tumors, their specificity, and their potential significance. It also presents the evidence for the existence of specific, cell-mediated immunity, both in vivo and in vitro , against tumor-associated cell surface antigens. There is considerable evidence for the role of immune cells in the resistance of the host to tumor growth. The chapter discusses the possible role of assays in the diagnosis, prognosis, and therapy of cancer.

Reoviruslike Agent in Stools: Association with Infantile Diarrhea and Development of Serologic Tests

Abstract: Reoviruslike particles were visualized by electron microscopy in stool filtrates prepared from stools of infants and young children with severe acute gastroenteritis. Patients who had such particles in their stools and whose paired acute and convalescent serums were tested developed an antibody response to the reoviruslike agent, which was measured by immune electron microscopy and by complement fixation. The reoviruslike agent was antigenically related to the epizootic diarrhea of infant mice virus and the Nebraska calf diarrhea virus.

Immunoaffinity chromatography of proteins.

Abstract: Publisher Summary In principle, protein antigen X, contained in a mixture of many other proteins, will bind selectively to insolubilized anti-X immunoglobulin (IgG). The other proteins for which the antibody has no affinity can be washed away and discarded. Thereafter, protein X is eluted from the adsorbent under conditions that disrupt the immune complex. The procedure has become widely applicable, having been developed for the purification of a variety of enzymes and other proteins. To establish such a procedure for the purification of hypothetical protein, X, the primary required reagent is specific anti-X antibody, covalently bound to an insoluble matrix. In addition, one must establish chromatographic conditions that permit only specific binding of protein X to a column of the immunoadsorbent. Thus, a similar column containing covalently linked nonimmune IgG should bind little or no protein X. Moreover, under ideal conditions, X will be the only macromolecule binding to the specific immunoadsorbent. Because of strong antigen binding, elution conditions which, of necessity, may not be as gentle as in ionic adsorption chromatography, and must be both sufficiently drastic to remove the protein completely and sufficiently gentle to permit its isolation in biologically active form.

In vivo localisation of radiolabelled antibodies to carcinoembryonic antigen in human colon carcinoma grafted into nude mice.

Abstract: SEVERAL attempts have been made to show the specific localisation in vivo of anti-tumour antibodies. Most of these studies, however, either in experimental animals1,2 or in humans3 were performed with antibodies obtained by adsorption and elution from poorly characterised crude tumour fractions.

THE INTERACTION OF IgE WITH RAT BASOPHILIC LEUKEMIA CELLS I. EVIDENCE FOR SPECIFIC BINDING OF IgE

Abstract: A rat basophilic leukemia cell line originally described by Eccleston et al. (3) has been successfully transplanted into eight Wistar strains and adapted to suspension cell culture without noticeable morphological changes. The cells deplete the reaginic activity of mouse and rat immune sera to an extent roughly equivalent to that reported for normal rat mast cells. Studies utilizing radioiodinated antilight-chain antibodies and radioiodinated partially purified rat IgE indicate that the cells bind IgE to their surface membrane with high specificity. Heating or mildly reducing the rat IgE destroyed its binding activity. The binding is unaffected by the presence or absence of Ca(++) and Mg(++), and is markedly inhibited by reaginic but not by normal rat or mouse serums. The affinity of these cells for human IgE, if present at all, is substantially lower than for rat IgE.

T-Cell Mediated Immunopathology in Viral Infections

Abstract: Virus-specific cytotoxic T cells are crucially involved in host recovery from primary infection Due to the immunological destruction of infected host cells, immunopathological damage may determine the severity of disease caused by poorly cytopathic or non-cytopathic viruses Some forms of virally induced hepatitis or of acquired immunodeficiency may be mediated by immunopathologically active virus-specific T cells

Human Serology in Chlamydia trachomatis Infection with Microimmunofluorescence

Abstract: were from various areas of the world and from whom a TRIC-LGV organism had been isolated were tested. (All isolates had been typed and included all presently recognized immunotypes except type A.) Of the patients tested, 94% had a titer of antibody of > 1:8 against at least one of the 13 antigens used, always including the type isolated. Seventy-nine percent of sera showed a type-specific antibody response, while 15% had a pattern of multiple antibody response that precluded a specific type diagnosis. Among the 6% of patients without evident antibody, all but one were males with mild urethritis. Patients who had classical LGV infection with buboes had antibody to more than one type, often in very high titer. The possibility of rapid disappearance of microimmunofluorescent antibody after

Mechanism of thymus-independent immunocyte triggering : mitogenic activation of b cells results in specific immune responses

Abstract: The present experiments were performed in order to analyze the mechanism by which thymus-independent antigens (nonspecific B-cell mitogens) can induce specific immune responses to antigenic determinants present on the same molecule. The hapten NNP was coupled to the B-cell mitogen, lipopolysaccharide (LPS). The conjugate retained full mitogenic activity and bound specifically to NNP-reactive cells. NNP-LPS activated polyclonal as well as specific anti-NNP antibody synthesis, but the optimal concentrations for induction of specific anti-NNP cells were several orders of magnitude lower than the concentrations required for polyclonal activation. These low concentrations failed to activate nonspecific cells, but they induced specific thymus-independent responses of high-avidity NNP-specific cells with the typical kinetics of antigenic responses in vitro. Furthermore, hapten-specific cells were paralyzed by NNP-LPS concentrations that were optimal for induction of polyclonal activation. Specific activation and paralysis could be abolished by free hapten indicating that selective binding of NNP-LPS to hapten-specific cells was responsible for the specificity of the response. However, the triggering signal lacked specificity, since high-avidity specific anti-NNP cells could still be activated by stimulating concentrations of NNP-LPS in the presence of free hapten, even though the Ig receptor combining sites were presumably occupied by NNP. The findings show that B cells with specific Ig receptors for the antigenic determinants on mitogen molecules preferentially bind these molecules and become activated at concentrations still unsufficient to trigger other B cells that lack specific receptors. It is suggested that activation for primary IgM responses in B cells is the result of "one nonspecific signal." This nonspecific signal is provided by the mitogenic properties of some antigens (highly thymus independent or, alternatively, by nonspecific T-cell factors (for highly T cell-dependent antigens), or both, and the surface structures responsible for triggering are not the Ig receptors. The specific Ig receptors only act as passive focusing devices for nonspecific stimuli, entitling the cell to be selectively activated, even though both the signal and the receptors for the triggering are nonspecific.

Activation of T and B lymphocytes in vitro. II. Biological and biochemical properties of an allogeneic effect factor (AEF) active in triggering specific B lymphocytes.

Abstract: The studies presented herein have focused on the biological and biochemical properties of a nonspecific mediator produced by populations of activated T lymphocytes during short-term in vitro reactions with foreign alloantigens. We have analyzed the activity of the unseparated and of chromatographically separated fractions of the supernatants from such cultures on the in vitro responses of mouse lymphocytes to soluble and macrophage-bound DNP-carrier conjugates and also to particulate heterologous erythrocytes. The results demonstrate that a highly active protein moiety, termed allogeneic effect factors (AEF), in the mol wt range of 30,000-40,000, is capable of acting directly on B lymphocytes, in the presence of antigen, probably to effect triggering and subsequent differentiation and proliferation to antibody-forming cells in vitro. The active molecule, although not manifesting specificity for antigen, does exhibit some strain-specific properties suggesting a possible relationship to cell surface antigens or other gene products coded in the major histocompatibility gene complex.

Photoscan Localization of GW-39 Tumors in Hamsters Using Radiolabeled Anticarcinoembryonic Antigen Immunoglobulin G

Abstract: Summary Photoscans and organ radioactivity were assessed in hamsters bearing cheek pouch grafts of a carcinoembryonic antigen (CEA)-producing human colonic carcinoma, GW-39; a human sarcoma, H.S.1; and a hamster amelanotic melanoma, A.Mel.3. The animals were given injections of 10 to 50 μCi 125I-labeled heterospecific anti-CEA immunoglobulin G (IgG) or normal IgG. The photoscans showed an increased uptake of radioactivity over the tumors and frequently over the areas of the thorax and urinary bladder, regardless of the tumor or the radiolabeled IgG preparation used. Even normal hamsters receiving either radiolabeled preparation showed an increased accretion of radioactivity over the thoracic region. A specific tumor localization, however, was demonstrated in animals bearing small ( The radioactivity recovered from GW-39 tumors borne in hamsters given injections of radiolabeled anti-CEA IgG revealed an increase of 7.5 to 20 times that recovered from other tissues. A slightly increased uptake of either the specific or nonspecific radiolabeled preparation was seen in the other, non-CEA-producing tumors studied, which was sufficiently increased over background radiation to permit visualization of the tumors by photoscanning, especially when the neoplasms were large and vascular. Evidently radiolabeled nonantibody components of heterospecific IgG can be localized in certain tumors and normal tissues by photoscanning. Nevertheless, tumor localization due to an antigen-antibody reaction, as we have found in CEA-producing GW-39 tumors treated with an anti-CEA antibody preparation, permits photoscan visualization of tumors too small to be demonstrated by radiolabeled normal IgG. It thus appears that CEA is a suitable tumor target for radioantibody by photoscanning.

Evidence for the expression of Ia (H-2-associated) antigens on thymus-derived lymphocytes

Abstract: We have demonstrated in an anti-Ia serum the presence of specific antibodies reacting with T cells, as well as with B cells, using a highly sensitive dye exclusion test. This antiserum reacts with both spleen and lymph node in a characteristic biphasic titration curve killing up to 70% of these cells. It also reacts with cortisone-resistant thymocytes. The A.TH-α-A.TL serum can be absorbed with spleen, lymph node, cortisone-resistant thymus, or normal thymus cells. Further in vivo absorptions in BALB/c nude cannot remove all of the cytotoxic activity for normal BALB lymph node lymphocytes, while completely removing the activity for nude cells. A Thy-1 positive cell line derived from a C57Br leukemia is reactive with this anti-Ia serum.