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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After lethal irradiation long-lived, immunologically vigorous C3Hf mice were produced by treatment with syngeneic fetal liver cells or syngeneic newborn or adult spleen cells. Treatment of lethally irradiated mice with syngeneic or allogeneic newborn thymus cells or allogeneic newborn or adult spleen cells regularly led to fatal secondary disease or graft-versus-host reactions. Treatment of the lethally irradiated mice with fetal liver cells regularly yielded long-lived, immunologically vigorous chimeras. The introduction of the fetal liver cells into the irradiated mice appeared to be followed by development of immunological tolerance of the donor cells. The findings suggest that T-cells at an early stage of differentiation are more susceptible to tolerance induction than are T-lymphocytes at later stages of differentiation. These investigations turned up a perplexing paradox which suggests that high doses of irradiation may injure the thymic stroma, rendering it less capable of supporting certain T-cell populations in the peripheral lymphoid tissue. Alternatively, the higher and not the lower dose of irradiation may have eliminated a host cell not readily derived from fetal liver precursors which represents an important helper cell in certain cell-mediated immune functions, e.g., graft-versus-host reactions, but which is not important in others, e.g., allograft rejections. The higher dose of lethal irradiation did not permit development or maintenance of a population of spleen cells that could initiate graft-versus-host reactions but did permit the development of a population of donor cells capable of achieving vigorous allograft rejection. These observations contribute to understanding of some of the persisting immunodeficiencies that are observed in man after fatal irradiation and bone marrow transplantation. These results should suggest better approaches to more effective cellular engineering for correction of immunodeficiency diseases and for treatment of immunodeficiency diseases and of leukemias and malignancies of man.
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PMID:Protection of lethally irradiated mice with allogeneic fetal liver cells: influence of irradiation dose on immunologic reconstitution. 0 Jun 73

Experiments were designed to determine which actual differences in the cellular composition between fetal liver and bone marrow account for the distinct types of graft-versus-host (GvH) disease. The assay of reactive lymphocytes (by in vitro mitogenic stimulation) in fetal liver transplants in mice, the purification of hemopoietic stem cells (HSC) of the transplants, and the quantitation of HSC numbers in the grafts traced the basis for the distinctly weak type of GvH disease after fetal liver cell grafts. It was found that transplantation of purified HSC concentrates did not modify the severity of GvH mortality. The moderate character of the delayed GvH disease was shown to depend on the presence of an HSC population in fetal liver with different qualities and not on numerical differences between the HSC in fetal liver and bone marrow. Data collected also demonstrated that when GvH disease occurred in the recipients of transplants of fetal liver, it shared the characteristic histologic features of the bone marrow GvH syndrome. The recovery of mitogen responsiveness of spleen cells may have been delayed in fetal liver allotransplantation as compared to syngeneic grafting. By supportive infusion of lymphoid cells, it was suggested that the immunodeficiency coinciding with GvH disease represented a secondary manifestation of the disease rather than a primary impairment in lymphoid differentiation.
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PMID:Nature of the delayed graft-versus-host reactivity of fetal liver cell transplants in mice. 1 32

The incidence of malignant tumors in the primary immunodeficiency diseases is dramatically increased. Four patients with primary immunodeficiencies who developed fatal malignancies are reported. Lymphoreticular tumors and leukemia predominate in most conditions, but epithelial neoplasms are the most common tumors in selective Iga deficiency, and they comprise over one-fourth of malignancies in common variable immunodeficiency. With the exception of common variable immunodeficiency and the Wiskott-Aldrich syndrome, hyperplasia of lymphoid tissue usually does not occur. Lymph node enlargement in any of the other immunodeficiencies is therefore most likely secondary to malignancy. Benign gastrointestinal nodular lymphoid hyperplasia occurs frequently in common variable immunodeficiency and in some instances may be impossible to differentiate roentgenologically from lymphoma.
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PMID:Primary immunodeficiency diseases and malignancy. 4 31

We have investigated a new hypothesis for the association between adenosine deaminase (A.D.A.) deficiency and immunodeficiency--namely, that deoxyadenosine rather than adenosine (an equally effective A.D.A. substrate) is toxic to proliferating cells of lymphoid origin. This possibility was explored in mitogen-stimulated lymphocytes cultured with a potent A.D.A. inhibitor, E.H.N.A. (erythro-9[2-hydroxy-3-nonyl] adenine) to simulate A.D.A. deficiency. In this in-vitro system deoxyadenosine was inhibitory at much lower and more physiological concentrations (1 mumol/1), compared with adenosine (100 mumol/1).
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PMID:A role for purine metabolism in the immune response: Adenosine-deaminase activity and deoxyadenosine catabolism. 7 65

A 13-month-old boy had a "late-onset" form of combined immunodeficiency and a fulminant Pneumocystis carinii pneumonia of one month's duration. There was no evidence of cutaneous-delayed hypersensitivity responses to diphtheria-tetanus toxoids, Candida albicans, or streptokinase-streptodornase, or of lymphocyte DNA synthesis after in vitro stimulation with the mitogens phytohemagglutinin and concanavalin A, and only 2% to 4% of peripheral blood E-rosetted T lymphocytes. The serum IgM level was normal (62 mg/dL), whereas the other immunoglobulins were markedly reduced. Despite an increased number of Ig-bearing lymphocytes, in vitro Ig secretion after pokeweed mitogen stimulation was substantially reduced. The thymus gland was dysplastic with no Hassalls' corpuscles or thymocytes, and other lymphoid organs showed depletion of T-dependent areas to a greater extent than the B-dependent areas.
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PMID:Diagnostic dilemma of a 13-month-old boy with 'late-onset' combined immunodeficiency. 8 98

The immunoglobulin constituents of hypertrophied lymphoid nodules in the intestinal tracts of six patients with the variable immunodeficiency syndrome and one patient with selective IgA deficiency were evaluated by the peroxidase-labeled antibody technique. The nodules were found to contain a dense population of IgM-bearing lymphocytes and much intercellular IgM. Evidence that the cells were engaged in IgM synthesis was the presence of the immunoglobulin in the perinuclear spaces and endoplasmic reticulum. Most of the IgM lymphocytes also had surface membrane IgM, and both kappa and lambda light chains were found in lymphocytes of individual nodules. Only a few cells containing IgD, IgG, or J chain, and none containing IgA, were found. We conclude that the intestinal lymphoid nodules associated with hypogammaglobulinemic states are populated principally by IgM B-lymphocytes of polyclonal origin.
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PMID:Immunocytochemical characterization of the lymphocytes in nodular lymphoid hyperplasia of the bowel. 10 8

The immunodeficient state associated with adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) deficiency may result from the selective phosphorylation by thymus-derived lymphocytes of the ADA substrate deoxyadenosine and the PNP substrate deoxyguanosine, leading to the intracellular trapping of toxic deoxyribonucleoside triphosphates. Agents such as deoxycytidine might be able to favourably modify the immunodeficient state by inhibiting deoxyribonucleoside phosphorylation. Deficiencies of other nucleotide catabolic enzymes, if selectively expressed by lymphocytes, might also lead to immunodeficiency via nucleoside trapping in lymphoid tissues. Purine deoxyribonucleoside analogues, either alone or in combination with ADA inhibitors, may have value as lymphospecific antimetabolites.
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PMID:Deoxyribonucleoside toxicity in adenosine deaminase and purine nucleoside phosphorylase deficiency: implications for the development of new immunosuppressive agents. 11 60

Deoxyadenosine and deoxyguanosine are toxic to human lymphoid cells in culture and have been implicated in the pathogenesis of the immunodeficiency states associated with adenosine deaminase and purine nucleoside phosphorylase deficiency, respectively. We have studied the relative incorporation of several labeled nucleosides into DNA and into nucleotide pools to further elucidate the mechanism of deoxyribonucleoside toxicity. In the presence of an inhibitor of adenosine deaminase [erythro-9-(2-hydroxy-3-nonyl)adenine [EHNA], 5 muM], deoxyadenosine (1-50 muM) progressively decreased the incorporation of thymidine, uridine, and deoxyuridine into DNA, but did not affect uridine incorporation into RNA. This decrease in DNA synthesis was associated with increasing dATP and decreasing dCTP pools. Likewise, incubation of cells with deoxyguanosine caused an elevation of dGTP, depletion of dCTP, and inhibition of DNA synthesis. To test the hypothesis that dATP and dGTP accumulation inhibit DNA synthesis by inhibiting the enzyme ribonucleotide reductase, simultaneous rates of incorporation of [(3)H]uridine and [(14)C]thymidine into DNA were measured in the presence of deoxyadenosine plus EHNA or deoxyguanosine, and in the presence of hydroxyurea, a known inhibitor of ribonucleotide reductase. Hydroxyurea (100 muM) and deoxyguanosine (10 muM) decreased the incorporation of [(3)H]uridine but not of [(14)C]thymidine into DNA; both compounds also substantially increased [(3)H]cytidine incorporation into the ribonucleotide pool while reducing incorporation into the deoxyribonucleotide pool. In contrast, deoxyadenosine plus EHNA did not show this differential inhibition of [(3)H]uridine incorporation into DNA, and the alteration in [(3)H]cytidine incorporation into nucleotide pools was less impressive. These data show an association between accumulation of dATP or dGTP and a primary inhibition of DNA synthesis, and they provide support for ribonucleotide reductase inhibition as the mechanism responsible for deoxyguanosine toxicity. Deoxyadenosine toxicity, however, appears to result from another, or perhaps a combination of, molecular event(s).
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PMID:Purinogenic immunodeficiency diseases. Differential effects of deoxyadenosine and deoxyguanosine on DNA synthesis in human T lymphoblasts. 11 1

Answers are beginning to emerge to the questions posed in the introduction to the preceding section. In vitro techniques that allow characterization of malignant cells have particular relevance when, as in Hodgkin's disease, the precise identity of the cells remains in doubt. Monolayer tissue cultures derived from Hodgkin's disease tumours and maintained as established cell lines have proven amenable to a variety of cytogenetic, immunological, enzymatic, and ultrastructural studies. Tissue culture experiemnts, in conjunction with meticulous immunological studies of individual Reed-Sternberg cells from non-cultured tumours, suggest that neoplastic cells of Hodgkin's disease are related to, and possibly derived from, cells of the monocyte-macrophage system. The lymphocytes that comprise an integral part of the cellular proliferation and form the basis for histological subclassification of the tumour could be a manifestation of cell-mediated immunity against this non-lymphoid malignant cell. The immunodeficiency of patients with untreated Hodgkin's disease of limited anatomical extent is not the primary event of the disorder and probably not related to the site at which the aetiological agent acts. The deficit does not result solely from impaired T-cell function and appears to arise as a consequence of excessive suppressor cell activity. Inhibitory monocyte-lymphocyte interactions may be one of the causes of defective cell-mediated immunity in Hodgkin's disease. The possible significance of elevated levels of circulating immune complexes in the serum of patients with Hodgkin's disease is indicated by the finding that such complexes react with cells of long-term monolayer tissue cultures derived from the tumour. Circulating immune complexes may be one source for intracellular immunoglobulin in non-cultured Hodgkin's disease cells. The presence of polyclonal immunoglobulin G on the membrane and within the cytoplasm of Reed-Sternberg cells could be due to in vivo binding and ingestion of immune complexes by such cells. The specificity of the interaction between soluble complement-containing immune complexes and neoplastic cells of Hodgkin's disease depends on the nature of the complexed antigen. The complexes could non-specifically attach via an Fc receptor or, if the complexed antigen is identical to a tumour cell antigen, the binding could be specific. If the immune complexes are tumour specific they could provide a source for isolation and identification of tumour-associated antigens. However, the aetiological significance of antigens and putative oncogenic viruses thus far identified in association with Hodgkin's disease remains to be clarified.
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PMID:The immunopathology of Hodgkin's disease. 15 50

The extent of suppression of antibody response by bursectomy (Bx) was examined as a measure of the seeding sequence of different clones from the bursa to peripheral lymphoid tissues. Chickens were bursectomized surgically 1, 4 or 7 days after hatching and immunized later with four antigens: sheep red blood cells (SRBC); Bordetella pertussis (Bp); human serum albumin (HSA); influenza virus (IV). The kinetics of the antibody responses were delayed in bursectomized birds when compared with the control groups. The following order in the degree of immunosuppression was established: Bp greater than HSA greater than SRBC greater than IV. This is discussed in relation to the 'sequential maturation' theory of ontogenesis of immunocyte differentiation. The data also stress the limitation of non-specific markers for assessing partial immunodeficiency states.
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PMID:Immunodeficiency in the chicken. I. Disparity in suppression of antibody responses to various antigens following surgical bursectomy. 16 36


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