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

Previously, we demonstrated that cultures of human peripheral blood lymphocytes (PBL) stimulated with herpes simplex virus type 1 (HSV-1) generate antigen-specific, major histocompatibility complex (MHC) restricted cytotoxic T lymphocytes (CTL) that tend to be CD4+ and restricted to HLA-DR antigens. In this study, we present evidence that when HSV-1 stimulated human peripheral blood lymphocytes (PBL) are cocultured with human immunodeficiency virus type 1 (HIV-1), the generation of CD4+, DR-restricted CTL during the 5-day culture period is inhibited. In contrast, HIV-1 had no effect on either natural killer (NK) activity, or on the unrestricted NK-like killers which are often detected in HSV-1-stimulated cultures after the depletion of CD16+ cells. HIV-1 also failed to inhibit the generation of CTL against Epstein-Barr virus (EBV), a response that principally involves CD8+, CD4-, class I-restricted killers.
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PMID:Inhibition of the in vitro generation of class II-restricted, HSV-1-specific, CD4+ CTL by HIV-1. 215 37

The measurement of cell-mediated immunity against the etiologic agent of human AIDS (HIV) in the non-human primate model of AIDS (simian immunodeficiency virus, SIV) has been difficult. In general, culture of peripheral blood mononuclear cells from HIV-1- and SIV-infected humans and monkeys, respectively, with purified inactivated HIV and SIV virus preparations has given inconsistent or negative proliferative responses. However, we describe herein an assay which consists of coculturing monocytes that have been pulsed with inactivated SIVsmm with nylon-wool-purified autologous T cells, leading to antigen-specific T-cell proliferation. The proliferative response, which predominantly occurs in CD4+ T cells, is major histocompatibility complex (MHC) class II-restricted and requires antigen processing. This assay will greatly facilitate the identification of the immunodominant epitopes recognized by T cells in sooty mangabeys, which are naturally infected but remain clinically asymptomatic, and in rhesus macaques, in which experimental infection leads to clinical symptomatology similar to human AIDS, eventually resulting in death.
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PMID:Requirements for simian immunodeficiency virus antigen-specific in vitro proliferation of T cells from infected rhesus macaques and sooty mangabeys. 216 18

Current evidence indicates that natural killer (NK) cells, which are large granular lymphocytes that mediate non-major histocompatibility complex (MHC)-restricted cytotoxicity and antibody-dependent cytotoxicity and that are involved in multiple regulatory, developmental, and immunologic processes, are important in health. Immunodeficiency states presenting with low NK activity are often associated with malignancies, chronic viral infections, or autoimmune diseases. Monitoring of NK function appears to be indicated as an aid to diagnosis, prognosis, and follow-up after therapy. Reliable performance of NK assays in a clinical laboratory requires that uniform criteria be established and followed for the acceptability of results. Statistical analysis of daily variability can be of great assistance in identifying and tracking sources of error, but routine statistical adjustments are not generally advisable. The quality control program described here provides a degree of assurance that this cytotoxicity assay can be dependable whether performed at one time point or serially. The successful implementation of this program requires laboratory resources, biostatistical support, and interpretative skills, all of which are available in a modern clinical laboratory.
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PMID:Natural killer cytotoxicity in the diagnosis of immune dysfunction: criteria for a reproducible assay. 217 1

To reduce the risks of immunization with killed or live attenuated virus vaccines, it may be advantageous to use a pure, defined antigen that contains determinants for both humoral and cellular immunity. However, although most non-living intact protein preparations induce antibodies and CD4+ major histocompatibility complex (MHC) class II-restricted helper and/or cytotoxic T lymphocytes (CTL), they do not elicit CD8+ MHC class I restricted CTL. Indeed, with a few exceptions, it has not so far been possible to induce CD8+ CTL by immunizing with intact soluble proteins. We show here that a single subcutaneous immunization in mice with immunostimulating complexes containing either purified intact gp160 envelope glycoprotein of the human immunodeficiency virus (HIV)-1 or influenza haemagglutinin results in reproducible and long-lasting priming of HIV specific or influenza-specific CD8+, MHC class I restricted CTL.
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PMID:Induction of CD8+ cytotoxic T cells by immunization with purified HIV-1 envelope protein in ISCOMs. 169 22

The class II major histocompatibility complex antigen deficiency syndrome is a rare immunodeficiency disease associated with defective expression of the class II antigens encoded for by the major histocompatibility complex. Clinically, this syndrome is manifest as a combined immunodeficiency presenting early in life, and affected individuals are susceptible to a variety of severe and/or opportunistic infections. Chronic, severe diarrhea and malabsorption are also characteristically found, and death is common within the first few years of life. Although the precise molecular lesions responsible for the failure of membrane antigen expression in this syndrome have not yet been identified, the pathogenetic mechanisms involve regulatory defects in the transcription of structural genes encoding for class II antigens. The absence of class II MHC antigens results in profound abnormalities in lymphocyte function and differentiation. Of central importance is the defective MHC-restricted interactions between CD4+ "helper" T lymphocytes and the various types of antigen-presenting cells found in the skin and elsewhere. The absence of class II MHC antigens also appears to alter the ability of affected B cells to be activated by a variety of membrane-mediated stimuli, and it profoundly disrupts both the intrathymic development and post-thymic differentiation of immunoregulatory T cells. This "experiment of nature" thus demonstrates the critical role of class II MHC antigens in the proper development and function of the immune system.
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PMID:The class II major histocompatibility complex antigen deficiency syndrome: consequences of absent class II major histocompatibility antigens for lymphocyte differentiation and function. 219 Oct 47

The infectivity of the human immunodeficiency virus (HIV) is related to the structure of its envelope protein, gp160, which is responsible for viral entry. We considered the possibility that a structural homology between gp160 and major histocompatibility complex (MHC) molecules might be associated with the extraordinary affinity that gp120 has for its receptor, CD4. Amino acid sequence comparisons revealed five regions of structural similarity between the HLA-DR beta molecule and gp160. The DR2 beta synthetic peptides containing these regions were examined for their ability to block HIV-induced syncytia formation using a 51Cr release assay. The peptide beta 141-155 inhibited the formation of syncytia whereas the other four DR beta peptides with gp160 similarity did not. Our results indicate that this region in gp120, which is similar to an HLA-DR region, is crucial to T cell-gp120 interactions, and should be considered in the design of future vaccines.
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PMID:HLA-DR peptide inhibits HIV-induced syncytia. 219 18

IgA deficiency is a common immunological disorder that is sometimes associated with an immunodeficiency syndrome, allergic disease, autoimmune disease and gluten enteropathy. Many subjects with this deficiency, however, are healthy, at least for many decades. Analysis of the immunological and genetic abnormalities found in IgA deficiency and in some of the associated disorders has led to the postulate that a genetically determined defect of immunoregulation underlies all of these diseases. Here, Martyn French and Roger Dawkins propose that the products of genes located within the central region of the major histocompatibility complex (MHC) regulate B cells and/or antibody production. Particular MHC ancestral haplotypes contain specific alleles and arrangements of these genes, thereby explaining associations with either increased or decreased production of immunoglobulin isotypes by B cells.
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PMID:Central MHC genes, IgA deficiency and autoimmune disease. 205 14

Natural killer (NK) cells have long been known to aid in the control of viral infections by killing virus-infected cells, including those infected with human immunodeficiency virus (HIV). Among the possible NK-susceptible target cells in an infected individual, the monocyte/macrophages are of special significance since they may serve as both a reservoir of HIV and aid in dissemination of the virus throughout the body. A new technique for the enrichment and cultivation of large numbers of recombinant interleukin 2 (rIL-2)-stimulated NK cells has been developed which provides cells with high cytotoxic activity. These IL-2-activated NK cells, adherent lymphokine-activated killer cells (A-LAK), can kill monocytes infected with HIV for 24 h to 7 days, with optimal target sensitivity between 3 and 7 days. Recognition and killing of the infected monocytes did not appear to be restricted by the major histocompatibility complex (MHC) antigens and could be cold-target inhibited by tumor cell lines. A-LAK cells may be useful in newer therapeutic approaches to treatment of HIV infection.
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PMID:Cytotoxic activity against HIV-infected monocytes by recombinant interleukin 2-activated natural killer cells. 222 37

Both infection with the human immunodeficiency virus type 1 (HIV) and zidovudine (formerly called azidothymidine [AZT]) cause myopathy. To identify criteria for distinguishing zidovudine-induced myopathy from that caused by primary HIV infection, we reviewed the histochemical, immunocytochemical, and electron-microscopical features of muscle-biopsy specimens from 20 HIV-positive patients with myopathy (15 of whom had been treated with zidovudine) and compared the findings with the patients' clinical course and response to various therapies. Among the zidovudine-treated patients, the myopathy responded to prednisone in four, to the discontinuation of zidovudine in eight, and to nonsteroidal anti-inflammatory drugs in two. Numerous "ragged-red" fibers, indicative of abnormal mitochondria with paracrystalline inclusions, were found in the biopsy specimens from the zidovudine-treated patients but not in those from the other patients. The number of these fibers appeared to correlate with the severity of the myopathy. All the patients, regardless of whether they had been treated with zidovudine, had inflammatory myopathy characterized by degenerating fibers, cytoplasmic bodies, and endomysial infiltrates consisting of CD8+ cells (mean +/- SD, 60.7 +/- 6.4 percent) and macrophages (39.2 +/- 6.4 percent) associated with Class I major histocompatibility complex (MHC-I) antigens (HLA-A, -B, and -C antigens) in the muscle fibers. The numbers and percentages of CD8+ cells and macrophages were similar in both the zidovudine-treated and the untreated HIV-positive patients. Specimens obtained on repeat muscle biopsy from two patients in whom the myopathy responded to the discontinuation of zidovudine showed remarkable histologic improvement. We conclude that long-term therapy with zidovudine can cause a toxic mitochondrial myopathy, which coexists with a T-cell-mediated inflammatory myopathy that is restricted to MHC-I antigen, and is indistinguishable from the myopathy associated with primary HIV infection or polymyositis in HIV-seronegative patients.
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PMID:Mitochondrial myopathy caused by long-term zidovudine therapy. 240 67

A hypothesis is presented in which HIV infection leads to immunodeficiency through indirect subversion of critical T cell regulatory mechanisms. Acting at the T cell receptor complex (TCR), viral components (gp120) mimic the natural ligands of CD4, molecules of the major histocompatibility complex (MHC), and deliver physiologically active, inappropriate signals resulting in generalized, uncontrolled lymphocyte activation, or "panergy." Clinical manifestations of panergy include autoimmune phenomena, lymphadenopathy, hyperglobulinemia, and symptoms mediated by lymphokines. Immunologic unresponsiveness occurs early in HIV infection prior to T cell depletion because activated cells do not respond to further stimulation. Ultimately, activation disrupts T cell homeostasis by interference with the generation of memory cells ("imnesia") and leads to net T cell loss, clonal deletion, and the development of AIDS. The clinical and immunologic features of HIV disease and AIDS are reviewed from this perspective. This hypothesis is consistent with the paucity of infected T cells, the clinical findings of both AIDS-related complex (ARC) and frank AIDS, the prolonged "incubation period," and a role for antigen-specific cofactors. Based on this view of HIV pathophysiology, therapeutic modalities should avoid immune stimulation and seek to block aberrant gp120 signals at CD4 and eliminate HIV-infected cells.
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PMID:AIDS as immune system activation. II. The panergic imnesia hypothesis. 240


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