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    ISSN: 1573-2592
    Keywords: Antigen uptake ; human monocytes ; tetanus toxoid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An absolute requirement for monocytes was demonstrated in the T-cell proliferative response to tetanus toxoid (TT) antigen. Antigen-pulsed monocytes were shown to be effective in triggering T-cell proliferation. Using125I-radiolabeled TT antigen, uptake by monocytes increased progressively over an 18-hr period, at which time 80–85% of the monocytes contained radiolabeled material. The ability of antigen-pulsed monocytes to trigger T-cell proliferation paralleled antigen uptake over an 18-hr period. Monocytes pulsed with antigen, then washed, lost their ability to trigger T-cell proliferation following a 24- to 48-hr culture period. Metabolic inhibitors blocked antigen uptake by monocytes and monocyte triggering of T-cell proliferation. Trypsin treatment of TT-pulsed monocytes did not affect the amount of antigen associated with monocytes or T-cell triggering by monocytes. Anti HLADR alloantibodies, which when added during antigen pulsing of monocytes inhibit the capacity of these monocytes to trigger T-cell proliferation, did not interfere with antigen uptake. These results indicate that human monocytes present antigen to T cells via an active process and in association with DR determinants, and that the immunogenic moiety of antigen does not remain indefinitely available to the T cell.
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  • 4
    ISSN: 1573-2592
    Keywords: Cell-mediated immune response ; idiopathic hypogammaglobulinemia ; common variable immunodeficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mononuclear cells from 39 patients with hypogammaglobulinemia of the common variable type were analyzed forin vitro proliferative responses to a panel of cell activators in order to examine the lymphocyte response to mitogens and to study the capacity to generate an immunologically specific secondary response. Patient lymphocyte response to phytohemagglutinin and concanavalin A was found to be significantly lower than that of controls studied in parallel (P〈0.01), and low response did not correlate with T-lymphocyte number. Response to pokeweed mitogen was significantly lower than that of controls (P〈0.01), but response to zinc, tested in a few patients, was normal. Strong depressions of patient lymphocyte proliferative responses toCandida albicans, Escherichia coli, andStaphylococcus aureus were observed (P〈0.01); all of these microbial activators require intact B-cell function for maximum response. Repeated testing of individual patients indicated that poor lymphocyte response could be consistently observed. Examination of changes inin vitro lymphocyte response during clinical course and disease management showed that a consistent pattern of intrinsic lymphocyte functional deficiency could be demonstrated.
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  • 5
    ISSN: 1573-2592
    Keywords: Lymphoma ; immunity ; antibodies ; vaccine ; pneumococcal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Eight patients with non-Hodgkin's lymphoma who have been in complete clinical remission for a mean of 23.3 months were evaluated for their antibody responses to a pneumococcal vaccine. The results were correlated with lymphocyte subpopulations, serum immunoglobulin levels, andin vitro mitogenic responses to phytohemagglutinin, concanavalin and pokeweed mitogen. Two patients with normal antibody responses had immunoglobulin levels and mitogenesis within the range of controls. Impaired antibody responses in the remaining six patients were correlated either with marked depressed mitogenesis to phytohemagglutinin or with low levels of IgA. Impaired humoral immune responses seem to persist in these patients even after several months of sustained clinical remission.
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  • 6
    ISSN: 1573-2592
    Keywords: Hypogammaglobulinemia ; autoimmune neutropenia ; autoimmune hemolytic anemia ; suppressor T cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Five patients with autoimmune blood dyscrasias and primary hypogammaglobulinemia are described. The autoimmune neutropenia in two patients rapidly responded to vincristine but was resistant to steroids. The three patients with autoimmune hemolytic anemia responded to steroids. Vincristine is therefore the drug of choice in patients with autoimmune neutropenia and hypogammaglobulinemia and is preferable to a trial of steroids in severely ill patients. Two of the patients had increased numbers of circulating T suppressor cells forin vitro immunoglobulin production. It is therefore unlikely that the autoimmunity in these patients is based on a lack of such suppressor cells.
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  • 7
    ISSN: 1573-2592
    Keywords: B lymphocytes ; antibody production ; suppressor cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Satisfactory experimental systems with which to study the antigen specific humoral immune response of human peripheral blood lymphocytes have not been available until recently. A commonly used method for the study of antibody production by human lymphocytes is that developed by Fauci and Pratt. This system is considered to be antigen nonspecific since the antigen against which the determined antibody is directed is not added to the cultures. We show here that the assumption of the Fauci-Pratt system being antigen nonspecific is not justified. An essential ingredient of this culture system is human serum that has been exhaustively absorbed with antigen (sheep red blood cells). This absorption procedure causes shedding of highly immunogenic antigenic fragments whose immunogenic activity we demonstrated using a recently developed antigen-dependent culture system. In the latter system, we have shown that the control of suppressor cells is a critical factor for the successful induction of antibody responses, particularly in view of the fact that lymphocyte mitogens must be added to cultured human lymphocytes to support their responsiveness. Appropriate timing of mitogen addition to the cultures was found to be an effective means of preferentially stimulating helper or suppressor activity. Pokeweed mitogen, a mitogen known to act on B and on T lymphocytes, stimulates B-cell responses readily but abrogates them prematurely by the simultaneous activation of suppressor cells. When pokeweed mitogen is added to an ongoing response with a delay of 48 hr, it enhances antibody responses markedly, presumably by providing additional help to B cells at a time when they have lost susceptibility to suppressor-cell effects.
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  • 8
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    Springer
    Journal of clinical immunology 1 (1981), S. 137-140 
    ISSN: 1573-2592
    Keywords: Marrow transplantation ; interferon ; Acyclovir ; Cyclosporin A
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Marrow transplantation for selected patients with leukemia, as for patients with severe combined immunologic deficiency or severe aplastic anemia, has now become an accepted clinical procedure. For patients with acute leukemia who have relapsed after achieving a remission of chemotherapy, marrow grafting from an identical twin or an HLA-identical sibling has now been demonstrated to produce median remissions as long as or longer than any reported for combination chemotherapy. In contrast to chemotherapy, marrow transplantation offers the possibility of cure for a small but significant fraction of these patients. Marrow transplantation for patients with ANL in first remission has now resulted in median survivals much longer than any reported with chemotherapy. Although it now appears that more than 50% of these patients can be cured with marrow transplantation, a much longer follow-up is indicated since some patients who achieve a complete remission with combination chemotherapy are now living for a long time, and some of these patients (less than 20%) may also be cured. Current intensive research with new modalities such as interferon, Acyclovir, Cyclosporin A, and monoclonal antibodies can reasonably be expected to improve the overall results of marrow transplantation.
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  • 9
    ISSN: 1573-2592
    Keywords: Immunodeficiency ; humoral ; hypogammaglobulinemia ; adenosine receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Since abnormal immune responsesin vivo may result from altered purine metabolism, we sought to delineate a potential role in humoral immunodeficiency for cells with specific adenosine membrane receptors. The purine nucleoside, adenosine, had been shown at low concentrationsin vitro to be capable of activating a subset of T lymphocytes to inhibit pokeweed mitogen (PWM)-driven IgG synthesis, while higher concentrations inhibited both IgG and IgM. Sixteen patients with common variable immunodeficiency and four patients with immunodeficiency with hyper-IgM were evaluated for the number of adenosine receptor cells in unfractionated mononuclear cells as well as T- and non-T-cell fractions. Theophylline-sensitive T cells, a subset of T lymphocytes which have been shown to be capable of suppressing immunoglobulin responsesin vitro, were also quantitated. Four of 16 patients with panhypogammaglobulinemia had clearly elevated levels of adenosine receptor cells. Two of these same individuals had low numbers of theophylline-sensitive cells, as did one patient with hyper-IgM. Only one person with variable immunodeficiency had increased theophylline-sensitive T cells. We found cases of clear-cut disparity between adenosine receptor and theophylline-sensitive cells. Furthermore, these markers segregated independently in both patients and normals. Finally, we assessed the effect of adenosine receptor cell removal onin vitro PWM-driven immunoglobulin synthesis. In none of the 20 patients tested did this cause a significant elevation of IgG or IgM production, nor did it have a consistent effect on cells from normals. Thus, while adenosine can be shown to profoundly alter immunoglobulin productionin vitro and some patients with humoral immunodeficiency have abnormal numbers of cells with adenosine receptors, we were unable to find evidence for a pathophysiologic role for these cells in immunoglobulin deficiency in humans.
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  • 10
    ISSN: 1573-2592
    Keywords: Natural killer cell ; OK-432 ; cancer patients ; interferon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recently, a streptococcal preparation, OK-432 has been used successfully as an immunopotentiator for immunotherapy in patients with malignant tumors in Japan. In this paper, we report that the administration of OK-432 augments the cytotoxic activity of peripheral blood lymphoid cells against a natural killer (NK) cell-sensitive erythroleukemic cell line, K562, in tumor patients. In patients before or after surgery, sufficient amounts of OK-432 strongly augmented the cytotoxic activity within 3 days after the initial administration of OK-432. Thereafter the levels of cytotoxicity declined rapidly. The administration of a lower dose of OK-432 gave a lower increase in cytotoxicity. Enhanced cytotoxicity occurred with the reintroduction of OK-432 but remained at lower levels of activity. Characterization and fractionation of OK-432-induced effector cells revealed that the augmented cytotoxicity seemed to be carried mainly by NK cells. A low titer of interferon was detected in 3 of 10 patients within 72 hr after the first inoculation of the agent. Furthermore, we discuss the potency of OK-432 for the induction of interferon in detail.
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