Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

T-cell epitopes are now well understood as amino-acid nonamers binding to major histocompatibility complex molecules. Powerful methods have been developed for their identification through screening of recombinant and synthetic peptides. Multiple epitopes from a single protein are valuable for detecting T-cell reactivity in disease, currently in human immunodeficiency virus infection, and in the future in autoimmune disease. Surprises are likely to be encountered while exploring the T-cell repertoire in this way, such as positive as well as negative selection of self-reactivity. T-epitopes are likely to find important applications in therapy, particularly in down-regulation of the immune response. Multiple mechanisms of down-regulation appear to operate, among which bystander suppression by TGF beta-producing T-cells from the gut is of great current interest.
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PMID:Where are peptides taking us in T-cell biology? 768 73

The intestinal (in particular rectal) mucosa is the main portal of entry for HIV in homosexual men, who represent the vast majority of HIV-infected patients in Europe and North America. There are several possibilities for HIV to reach the CD4-positive T cells, macrophages and follicular-dendritic cells in the intestinal mucosa. HIV may be transported through M-cells directly to mucosal lymph follicles. Alternatively HIV may infect enterocytes via Fc-receptor by antibody-bound HIV or via a CD4-independent receptor. By successive budding on the basolateral side of the enterocytes HIV may be released into the lamina propria. The loss and functional impairment of activated CD4-positive lamina propria T-cells could be responsible for both the decreased immune defense and altered structure and function of the mucosa. The common intestinal symptoms in HIV-infected patients may be caused by a variety of mechanisms. The high number of secondary opportunistic or non-opportunistic infections and secondary malignancies of the gut may be responsible for the observed symptoms. However, the pathogenic relevance of some of these pathogens is questionable since there is often no correlation between symptoms and presence of the pathogen. In addition, there is a considerable percentage of symptomatic patients without identifiable microorganisms. Yet unidentified pathogens, small intestinal bacterial overgrowth, damage of intestinal nerve fibres, or secretory diarrhea may contribute to the pathogenesis of gastrointestinal symptoms. The findings of a pathogen-negative diarrhea, of HIV-infected mononuclear cells in the gut, and of epithelial hypoproliferation and enterocyte dysmaturation is in agreement with the hypothesis that there is an enteropathy caused by HIV itself.
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PMID:[Gastrointestinal manifestations of HIV infection]. 791 Sep 96

This study was performed in 27 HIV-1+ children to characterize the IgA hyperglobulinaemia observed in the serum during the course of HIV-1 infection. By contrast with serum IgG, which increased very early, IgA elevation was related to the decrease of CD4+ cell percentage. It was demonstrated that IgA1 subclass increased selectively. Secretory IgA (SIgA) and IgA and IgG activity to gliadin, bovine serum albumin (BSA) and at a lower level to casein could be detected in the serum at the early stages of HIV infection, but SIgA levels and IgA activity to gliadin further increased during the course of immunodeficiency. By contrast, IgA and IgG activity to tetanus toxoid did not change. These data demonstrate that the hyper IgA, closely related to the degree of immunodeficiency, could be due in part to a disturbance of the gut mucosal immune system. Moreover, impaired intestinal immunity seems to appear very early, and to progress during the course of paediatric HIV-1 infection.
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PMID:Early impairment of gut mucosal immunity in HIV-1-infected children. 791 75

Human intestinal lamina propria T cells have a low expression of the CD45RA antigen and a high expression of the CD45RO antigen. This phenotype is characteristic for memory T cells. In addition, T cells in the effector compartment of the mucosa bear surface antigens that are very rarely found in other sites of the immune system. Intestinal T cells also express functional IL-2 receptors, and IL-2 receptor alpha-chain mRNA, and are able to synthesize high amounts of IL-2. However, other markers of memory T cells, as CD29, are not expressed in high density in the lamina propria, indicating that lamina propria T cells differ from "classical" memory T cells. This is supported by functional studies in nonhuman primates infected rectally with Chlamydia trachomatis that show that lamina propria T cells do not proliferate after stimulation with antigen but rather provide helper function for immunoglobulin synthesis. These findings indicate a specific state of differentiation of lamina propria T cells that is adapted to the specific requirements in the gut. In inflammatory bowel disease (IBD) and in celiac disease, an increase in the number of CD25-positive activated T cells is found in involved mucosa. It has been shown that mucosal T-cell activation induces epithelial cell damage and mucosal transformation. Thus, a T cell-mediated damage may contribute to the pathogenesis of IBD. HIV-infected patients have a decreased number of CD4-positive T cells in the intestinal lamina propria. The number of CD25-positive activated T cells is also significantly decreased in the intestine compared to controls. Correlating with the presence of HIV-infected mononuclear cells in the mucosa, mucosal atrophy with hyporegeneration and enterocyte dysmaturation is observed. HIV might thus cause impairment and depletion of activated regulatory T cells in the intestinal lamina propria, which could lead not only to a breakdown of the mucosal immune barrier, resulting in a variety of opportunistic infections, but also to malabsorption, due to mucosal atrophy or enterocyte dysfunction. These findings indicate a close relationship between mucosal T cells and enterocyte proliferation and maturation.
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PMID:Cell differentiation and proliferation in the gastrointestinal tract with respect to the local immune system. 797 5

AGIs are produced by plants and microorgansims in the environment. They are absorbed from the gut, distributed throughout the body and are concentrated inside cells. AGIs alter the glycan chains of cellular glycoproteins (CGP) during their formation so that the same CGP produced by different clones of cells (and hence with different glycan chains) becomes structurally the same. Prion protein (PrP), a CGP, is rendered indestructable to cellular mechanisms (as PrPi) by the TSE infective process; it is suggested that AGIs could both cause and prevent this by altering the primary structure of PrP. HIV envelope protein, gp120, carries glycan chains that are decided by the clone of the cells by which it is produced. Each cellular clone would be expected to add a specific group of glycan chains, making the gp120 antigenically separate. As HIV infection progresses, infected clone numbers rise, the antigenic diversity of gp120 may rise as would antibody production, trying to keep pace. Antigenically stimulated CD4+ cells carrying HIV genes, increase HIV production with gp120 antigenically different from its stimulant. AGIs prevent the glycan diversity and may prevent the extension of HIV infection.
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PMID:Alkaloidal glycosidase inhibitors (AGIs) as the cause of sporadic scrapie, and the potential treatment of both transmissible spongiform encephalopathies (TSEs) and human immunodeficiency virus (HIV) infection. 802 34

The most virulent primate lentivirus identified to date, the simian virus SIVsmmPBj14 (SIV-PBj14), is unique not only because it causes acute disease and death within days instead of months or years, but also because of its replicative and cellular activation properties. The acute disease syndrome has many features in common with primary HIV-1 disease, but differences in the respective outcomes of these two acute lentiviral infections appear to be linked to the rapidity with which SIV-PBj14 replicates and the high titers of virus that subsequently accumulate in lymphoid tissues. The most prominent pathologic feature of SIV-PBj14 is extensive lymphoid hyperplasia of T-cell zones, especially in the gut-associated lymphoid tissue. These expanded T-cell zones contain a high proportion of lymphoblasts, activated macrophages and syncytial cells, which are positively correlated with high numbers of SIV antigen-positive cells. Replication of the virus to high titers, accompanied by extensive cellular activation and proliferation, leading to high levels of cytokines, such as interleukin-6 and tumor necrosis factor-alpha, are consistent with acute inflammatory disease. The pathogenesis of SIV-PBj14 also appears to correlate most directly with some of its unique biologic properties, such as the ability to replicate in resting peripheral blood mononuclear cells, to activate lymphocytes, and to induce lymphocyte proliferation. Biologically and molecularly cloned viruses derived from SIV-PBj14 and isolates obtained from macaque PBj at earlier times, are being used to identify viral determinants that influence biologic and pathogenic properties of SIV-PBj14. Further characterization of this virus should provide new insights into lentivirus-cell interactions and their contributions to disease.
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PMID:Unique lentivirus--host interactions: SIVsmmPBj14 infection of macaques. 806 54

T cell subsets in the gut mucosa are distinct populations and their imbalance in HIV has specific implications in infection. Alterations in T cell subsets in duodenal biopsies were investigated in 17 asymptomatic HIV patients, 24 AIDS patients and 10 controls with non-ulcer dyspepsia. Immunohistochemistry and immunofluorescence using MoAbs to CD3, CD4, CD8, CD68, CD45RA, CD45RO and gp120 were performed on frozen sections. In the lamina propria, there was a significant depletion of CD4+ cells at all stages of HIV, but the density of CD8 lamina propria cells was increased. Intraepithelial lymphocytes were decreased in AIDS patients. There was a significant correlation between cellular density and mucosal CD3+ lymphocytes, and between mucosal CD3+ and CD8+ lymphocytes. Although mucosal CD4,CD45RO+ 'memory' cells were decreased, CD8,CD45RO+ 'memory' cells were increased. Mucosal CD4+ lymphocyte depletion occurred early in HIV, and thus their role in mucosal protection against opportunistic infection should be revised. Mucosal CD8+ lymphocytes initially increased, but decreased when CD4 blood counts were depleted, perhaps contributing to loss of host protection against infection. Intraepithelial lymphocyte depletion may also contribute to opportunistic infection.
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PMID:Loss of mucosal CD4 lymphocytes is an early feature of HIV infection. 809 58

Gastrointestinal pathogens are of three varieties, those that can, and often do, take the life of the host, those that infect transiently and rarely are life-threatening, and those (parasites) that establish a relatively prolonged residence or colonization of the host's alimentary tract. In the case of the second form, if infections are recurrent, both catabolic effects during the episode and failure to digest foods and/or absorb nutrients results. Similarly, catabolic wastage through activation of the acute phase response, and interference with the host's acquisition of nutrients by maldigestion, malabsorption, intestinal losses and competition with the parasite burden can impair growth and nutrition with helminthic infections. Growth and nutrition with respect to all of the macronutrients and virtually all of the micronutrients have been documented to be adversely affected by gastrointestinal pathogens. For its burgeoning importance as a worldwide health problem, both with the HIV virus as a direct intestinal pathogen and with the opportunistic gut infections occurring in the immunocompromised host, AIDS represents the emerging context of the impairment of nutritional status by intestinal pathogens.
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PMID:Pathways to the impairment of human nutritional status by gastrointestinal pathogens. 811 84

Cyclo(His-Pro) (CHP) is a gut-neuropeptide that influences both appetite and carbohydrate metabolism. This study was undertaken to determine whether concentrations of CHP correlated with various clinical markers of nutritional status and progression of HIV infection. Serum concentrations of CHP were analyzed in a clinical sample of 100 HIV-positive patients whose HIV clinical status ranged from asymptomatic to advanced disease with weight loss. We found a relationship between CHP concentrations and serum albumin and hemoglobin levels, markers of chronic nutrition and disease. However, no correlation was seen between CHP and cortisol concentrations, a marker of acute stress. To analyze the relationship of HIV clinical stage and CHP, patients were divided into three subgroups: asymptomatic, mildly symptomatic, and clear-cut AIDS. CHP concentrations were significantly correlated with HIV clinical stage. These data lead to the hypothesis that CHP is a marker of disease progression and that it potentially plays a role in modulating the nutrition of HIV-infected patients.
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PMID:Relationship between serum cyclo(His-Pro) concentrations and the nutritional status of HIV-infected patients. 813 57

Intestinal T cells have a unique state of activation and differentiation which might specifically affect or be affected by HIV infection. Lymphocyte subsets in the peripheral blood are well characterized, but our knowledge about intestinal lymphocytes in HIV infection is incomplete. We therefore analysed lymphocytes isolated from large intestine biopsies of AIDS patients and controls by three-colour cytofluorometry. In the large intestine of HIV-infected patients CD4 T cells were reduced and CD8 T cells were increased compared with controls. Most of the CD8 T cells in the colorectal mucosa of AIDS patients were of the cytotoxic phenotype. Activated and resting CD4 T cells were similarly reduced, the expression of CD25 and HLA-DR of CD8 T cells was unaltered and increased, respectively. In intestinal CD4 T cells the expression of CD29 was decreased, but the expression of CD45RO and HML-1 was normal. CD8 T cells had a decreased expression of all these differentiation markers. Our findings demonstrate substantial alterations in subset distribution, activation, and differentiation of large intestine T cells, which may contribute to the secondary infections and malignancies commonly observed in the gut of AIDS patients.
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PMID:Abnormalities in subset distribution, activation, and differentiation of T cells isolated from large intestine biopsies in HIV infection. The Berlin Diarrhoea/Wasting Syndrome Study Group. 813 40


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