Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with myeloma have a depressed capacity to respond to antigenic challenge. Studies in this laboratory have previously described an unclassified lymphoid cell which binds human erythrocytes coated with human immunoglobulin G (IgG) anti-D antibody (EA) as important in the inhibition of Ig synthesis in myeloma patients. Using monoclonal antibodies, two-color fluorescence studies, and flow cytometry, we characterized this EA cell as a Leu-1+ (cluster designation (CD) 5), Leu-12+ (CD 19), Leu-16+ (CD 20), B2+ (CD 21), Leu-14+ (CD 22), and HLA-DR+ B cell. The cell was negative for antibodies to Leu-2 (CD 8), Leu-3 (CD 4), Leu-4 (CD 3), Leu-5 (CD 2), Leu-7, Leu-8, Leu-11 (CD 16), Leu-M1 (CD 15), Leu-M3, and CALLA (CD 10). This profile is consistent with a Leu-1+ B cell and excludes a T cell, natural killer cell, and monocyte. Comparison of the relative role of these cells to the role of monocytes in the suppression of pokeweed mitogen-stimulated Ig synthesis was determined in serial studies on 19 myeloma patients. The mean (+/- SEM) percentage of inhibition of Ig synthesis by monocytes from stage I myeloma patients was 14 +/- 2.2%, from stage II patients was 37 +/- 3.5%, and from stage III patients was 51 +/- 4.7%. Inhibition of Ig synthesis by Leu-1+ EA cells was 46 +/- 1.5%, 48 +/- 1.6%, and 43 +/- 3.7% in stage I, II, and III patients, respectively. Immunosuppressive B cells are an important component of inhibition of Ig synthesis in the immunodeficiency of myeloma.
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PMID:Multiple myeloma: an immunologic profile. IV. The EA rosette-forming cell is a Leu-1 positive immunoregulatory B cell. 295 12

Previous studies have shown that cyclosporin (CSA) inhibits lymphoproliferation to cytomegalovirus (CMV)-infected, glutaraldehyde-fixed, and irradiated fibroblasts (CMVFFx) in vitro. Generation of cytotoxic cell activity is impaired in cultures with CSA, but the induction of suppressor cells is not. In the present studies we tested the ability of interleukin-2 (IL-2) and supernatants of lymphocytes stimulated by CMVFFx with or without CSA (1 microgram/ml) to restore functional activities of lymphocytes from primary cultures treated or not treated with CSA. IL-2 significantly enhanced lymphoproliferation, cell-mediated cytotoxicity to CMV-infected fibroblasts (CMVF), natural killer cell activity, and the activity of cells capable of suppressing the response of fresh autologous cells to CMVFFx of cells derived from control and CSA-treated primary cultures. IL-2 was found in day-2 supernatants of control cultures but not CSA-treated cultures. Day-2 control supernatants were capable of significantly enhancing proliferation and suppressor cell activity but were less efficient at restoring cytotoxic cell function. Day-2 supernatants from CSA-treated cultures were not able to enhance lymphoproliferation or cytotoxic cell function but did induce significant levels of suppressor cell activity. The results indicate the presence of different functional mediators in the culture supernatants. The ability of IL-2 to restore lymphocyte effector functions against a clinically important virus may have important therapeutic implications in the treatment of this viral infection in immunodeficiency diseases and in the restoration of immune competence after transplantation.
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PMID:Effect of cyclosporin and interleukin-2 on the restoration of in vitro immune responses to cytomegalovirus. 298 14

We have reported two patients with multiple primary cancers in the presence of normal tests of cellular immune function, including normal natural killer cell activity. Immunodeficiency has been associated with an increased incidence of neoplastic disorders, but the resulting malignancies are unique, consisting of non-Hodgkin's lymphomas and a limited number of carcinomas. Immunosuppressive therapy and AIDS have been associated with aggressive sarcomas. Immunocompetence is of major importance against certain tumors. On the other hand, in spite of the limitations of the clinical evaluation of immunologic function, immunocompetence is insufficient to protect against neoplasia.
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PMID:Multiple malignancies in immunocompetent patients. 320 3

The lungs of patients with acquired immunodeficiency syndrome (AIDS) are frequently affected by opportunistic and nonopportunistic infections and pulmonary localizations of Kaposi's sarcoma. The aim of this study was to verify whether, in patients with human immunodeficiency virus (HIV) infections, immunologic pulmonary abnormalities set the stage for the lung complications. For this purpose, a phenotypic and functional characterization of lymphocytes recovered from the bronchoalveolar lavage (BAL) fluid of 24 patients with clinical symptoms and signs of HIV infections was performed (six patients with constitutional disease, five patients with neurologic manifestations, and 13 patients with full-blown AIDS). Our data showed that (1) in patients with HIV, the percentage and absolute number of pulmonary CD8 cells were significantly increased over those in control subjects (in 25% of these patients, mostly with full-blown AIDS, CD8 cells sustained an alveolitis); (2) lung CD4 cells were reduced in percentage but not in absolute number, with the exception of patients with AIDS in whom a significant decrease of the absolute number of BAL CD4 cells has been found (further phenotypic analysis of CD4 lymphocytes showed a reduction of the expression of T4A, B, and E with respect to the T4, T4C, T4D, and T4F epitopes); (3) although the number of BAL cells bearing NK-related determinants was increased, we were unable to demonstrate any in vitro natural killer cell activity. We suggest that the impairment of a proper NK activity in the lungs of these patients might be central to the mechanisms leading to the in situ immunodeficiency state and to the pulmonary complications characterizing AIDS.
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PMID:Phenotypical and functional analysis of bronchoalveolar lavage lymphocytes in patients with HIV infection. 320 12

The peripheral lymphocytes of 50 cases of human immunodeficiency virus (HIV) infection (13 of acquired immune deficiency syndrome (AIDS), 17 of AIDS related complex (ARC), and 20 healthy carriers) were studied immunoultrastructurally. The prevalence of "tubuloreticular structures" and "tubular confronting cisternae" increased with the progression of the disease. Numerous tubular confronting cisternae were noted in patients presenting with a high serum acid labile alpha-interferon values. The patients with depressed natural killer cell activity were characterised by circulating immature natural killer cells with abundant multivesicular bodies that were devoid of "parallel tubular arrays". With an immunogold staining technique the location of HIV antigen was detected ultrastructurally, both at the surface of "hand-mirror" natural killer cell lymphocytes and inside vacuolised cells, probably corresponding to infected T4 lymphocytes. These findings indicate the usefulness of electron microscopic techniques in evaluating the pathology and the pathogenetic outcome of AIDS.
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PMID:Fifty cases of human immunodeficiency virus (HIV) infection: immunoultrastructural study of circulating lymphocytes. 334 80

Injection of rats with cyclophosphamide (CY) after their consumption of a novel saccharin-flavored drinking solution resulted in a conditioned aversion to saccharin and a conditioned suppression of natural killer cell (NKC) cytotoxicity. In this study, male Sprague-Dawley rats were conditioned by pairing saccharin with 50 mg/kg CY, an immunosuppressive drug with noxious gastrointestinal side-effects. Twenty-two and 26 days later, re-exposure of conditioned animals to saccharin alone re-enlisted the immunosuppressive effects of CY when NKC cytotoxicity was measured on day 29. Although CY also suppressed spleen cell number, IgG antibody titers and interleukin 2 (IL2) production, these immune responses did not appear to be affected by the behavioral conditioning paradigm in this experiment. Unique aspects of this study include the ability to measure multiple immune responses in a single rat and the finding that previous reports of behaviorally conditioned immunosuppression can be extended to another parameter, NKC cytotoxicity. These findings could have significant implications to human medicine, especially in the area of autoimmunity and immunodeficiency, and intervention and treatment of cancer.
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PMID:Cyclophosphamide-conditioned suppression of the natural killer cell response in rats. 349 Jun 76

NPT 15392 (Erythro-9 (2-hydroxy-3 nonyl) hypoxanthine), a novel heterocyclic immunomodulatory compound, was analyzed over a broad concentration range on a variety of human blood leukocyte functions in vitro. NPT 15392 augmented mitogen-induced lymphocyte transformation in a variable fashion; lymphocytes from 9 of 24 individuals showed significant stimulation with phytohemagglutinin at 0.01 microgram/ml of NPT 15392, and 3 of 14 and 3 of 3 showed similar augmentation with concanavalin A and pokeweed mitogen, respectively. NPT 15392 above 10 microgram/ml inhibited mitogen responses and did not itself stimulate cell division. NPT 15392 also augmented responses of lymphocytes to antigenic stimulation with Candida and Staphylococcus antigens, purified protein derivative, and allogeneic cells in a variable manner. When observed, stimulation occurred at 0.01-1 microgram/ml of NPT 15392 for Candida and Staph. and at 0.01 microgram/ml with PPD and allogeneic cells. NPT 15392 (0.01-1 microgram/ml) consistently induced suppressor cell function alone and in combination with concanavalin A. This effect is apparently mediated by T lymphocytes since suppression was not mediated by interferon, prostaglandin or histamine. In addition, NPT 15392 (0.01-10 microgram/ml) significantly augmented "active" T cell rosettes. NPT 15392 over a broad concentration range and in the presence and absence of interferon did not stimulate natural killer cell activity or antibody-dependent cellular cytotoxicity. The data indicate that NPT 15392 is a modulator of such T lymphocyte functions as proliferative response to antigen and mitogen, suppressor activity and receptor display. Such activities imply potential therapeutic use in immunodeficiency related to defects of the thymus and thymus-derived lymphocytes.
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PMID:Effects of NPT 15392 in vitro on human leukocyte functions. 617 91

Natural killer cells capable of lysing herpes simplex virus type 1 (HSV-1)-infected fibroblasts were studied in three groups of patients unusually susceptible to severe herpes-virus infections. Cord blood was evaluated because of the known susceptibility of neonates to disseminated infections due to herpes simplex virus type 2 at birth. Only 30% of the cord blood specimens tested demonstrated normal lysis of HSV-1-infected fibroblasts and a normal increment in the lysis of infected over uninfected cells. Five out of six patients with Wiskott-Aldrich Syndrome (WAS) also were found to have abnormally low responses by these criteria. The one WAS patient with normal responses had had little difficulty with infections and had survived much longer than usual. Five patients with severe herpesvirus infections and no known primary cellular immunodeficiency had natural killer cell function significantly below normal (P less than 0.001). These data suggest that natural killer cells probably play an important role in human resistance to herpesvirus infection and that deficiencies of this system may result in unusual susceptibility to herpesvirus infections.
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PMID:Correlation between low natural killing of fibroblasts infected with herpes simplex virus type 1 and susceptibility to herpesvirus infections. 630 2

The X-linked lymphoproliferative syndrome is characterized by immunodeficiency to Epstein-Barr virus (EBV) manifested by severe or fatal infectious mononucleosis and acquired immunodeficiency. We studied immune responses in six males of a well-characterized kindred with the X-linked lymphoproliferative syndrome. Two males were studied before and during acute fatal EBV infection. Both individuals demonstrated normal cellular and humoral immunity before EBV infection. During acute EBV infection, both individuals developed vigorous cytotoxic cellular responses against EBV-infected and -uninfected target cells. Anomalous killer and natural killer T cell activity was demonstrated against a variety of lymphoid cell lines, autologous fibroblasts and autologous hepatocytes. Effector cells responsible for anomalous killing reacted with a pan-T cell monoclonal antibody, and belonged to the OKT.8 T cell subset. Death in each case was caused by liver failure, but one patient developed extensive liver necrosis, whereas the other developed a massive infiltration of the liver with EBV-infected immunoblasts after aggressive immunosuppressive therapy. Immunological studies were performed on four males who had survived EBV infection years previously. They demonstrated global cellular immune defects with deficiencies of lymphocyte proliferative responses to mitogens and antigens, humoral immune deficiencies, abnormalities of regulatory T cell subsets and deficient natural killer cell activity. We propose that an aberrant immune response triggered by acute EBV infection results in unregulated anomalous killer and natural killer cell activity against EBV infected and uninfected cells. These studies suggest that global immune defects appearing in males with X-linked lymphoproliferative syndrome who survive EBV infection are epiphenomenon.
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PMID:X-linked lymphoproliferative syndrome. Natural history of the immunodeficiency. 630 53

Four previously healthy Danish homosexual men developed Kaposi's sarcoma or opportunistic infections with fever of unknown origin and lymphadenopathy. One patient died of a Pneumocystis carinii pneumonia. Three patients had defective cell-mediated immunity with absent leucocyte interferon production and decreased proliferative response to mitogens and antigens. T lymphocyte helper subsets and natural killer cell activity were reduced. Unstimulated mononuclear cells produced leucocyte migration inhibitor factor. Two patients were sexual partners and three had never been to the USA, where cases of severe acquired immunodeficiency have been reported. Thus, the syndrome must also be suspected in European homosexual men who present with fever of unknown origin, opportunistic infections, or Kaposi's sarcoma.
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PMID:Severe acquired immunodeficiency in European homosexual men. 680 93


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