Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009450 (infectious diseases)
 83,438 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infection of immunocompetent mice with Leishmania donovani is characterized by the development of a tissue granulomatous response, in vivo macrophage activation, and a predominantly Th1-type CD4+ T-cell response. To determine whether a recently described T-cell-independent pathway of gamma interferon (IFN-gamma) production involving the collaboration of macrophages and natural killer (NK) cells contributed to this pattern of events, we have investigated the responses of scid mice to L. donovani infection. The multiplication of parasites in the livers of scid mice progressed at a rate equivalent to that seen in BALB/c mice over the first 14 days of infection, but by day 28 scid mice had a fivefold-higher parasite burden. This infection was not, however, accompanied by any demonstrable histological response in the liver or by elevated major histocompatibility complex class II expression on splenic macrophages. In vitro, L. donovani was unable to trigger IFN-gamma production from scid spleen cell cultures under conditions which allowed efficient triggering by bacterial stimuli. Although L. donovani also failed to stimulate the release of tumor necrosis factor, an important macrophage-derived cofactor for IFN-gamma secretion by NK cells, exogenous recombinant tumor necrosis factor alpha could not restore the IFN-gamma response. Even with the potent synergistic effect of exogenous interleukin-2, L. donovani was unable to stimulate this pathway to the same extent as Listeria monocytogenes. Indeed, L. donovani inhibited the response to L. monocytogenes in a dose-dependent fashion. Experiments involving the transfer of supernatants and the use of neutralizing monoclonal antibodies have failed to find evidence that interleukin-10 is involved in this inhibition. These data suggest that NK cell-derived IFN-gamma is unlikely to participate in the early regulation of visceral leishmaniasis in the mouse.
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PMID:Leishmania donovani infection in scid mice: lack of tissue response and in vivo macrophage activation correlates with failure to trigger natural killer cell-derived gamma interferon production in vitro. 139 44

Non-major histocompatibility complex (MHC) restricted cytotoxicity is an important part of the immune reaction mounted in response to bovine herpes virus type 1 (BHV-1) infection. In this study, we evaluated the effect of BHV-1 infection on the ability of lung parenchyma leucocytes (LPL), cranial tracheobronchial lymph node cells (BLNC) and peripheral blood mononuclear leucocytes (PBML) to mediate this function. While LPL from non-infected calves mediated cytotoxicity against BHV-1-infected cells, a similar activity could not be detected in PBML or BLNC. In contrast, both LPL and PBML from naive calves could mediate cytotoxicity against K562 target cells but only after activation with interleukin-2 (IL-2). BLNC were unable to kill K562 cells. Infection of calves with BHV-1 enhanced the ability of LPL and PBML to kill BHV-1-infected cells. This enhancement was detected as early as Day 1 after infection in LPL whereas it could only be detected in PBML 8 days after infection. The results demonstrate that the leucocyte population present at the site of infection was able to mediate a potentially important antiviral function and that this function was enhanced rapidly in response to infection. Thus LPL-mediated cytotoxicity may be an important mechanism for the recovery from BHV-1 infection.
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PMID:Cell-mediated cytotoxic responses in lungs following a primary bovine herpes virus type 1 infection. 153 2

Infection is a major cause of morbidity following severe head injury. Although investigations have demonstrated central nervous system modulation of immune function, the effects of severe head injury on immune activity have not been well documented. This study prospectively investigated cellular immune function in 20 patients with isolated severe head injury. In vivo cellular immune status was determined by responses to delayed-type hypersensitivity (DTH) skin tests. In vitro studies included the effect of the lymphocyte mitogen, phytohaemagglutinin (PHA), on peripheral blood lymphocyte (PBL) phenotype expression and PBL blastogenesis. DTH skin testing demonstrated anergy to all antigens used during the first two weeks following head injury. Analysis of PBLs incubated with PHA demonstrated a decrease in the percent of PBL blastogenesis (p = 0.002), the percentage of cells marking as T-cells (p = 0.018), helper T-cells (p less than 0.001) and those expressing interleukin-2 receptors (p less than 0.001). There was a significant increase in the percentage of cells that marked as monocytes (p = 0.030), whereas there was no significant change in the percentage of B-cells, suppressor/cytotoxic T-cells, natural killer cells or in cells expressing the HLA-DR antigen. The infection rate was 55% with most occurring within 5 days of injury. The results of this study suggest that isolated severe head injury causes suppression of cellular immunity. The decrease in PHA stimulated PBL blastogenesis, helper T-cell phenotypic and interleukin-2 receptor expression, suggests suppression in early helper T-cell activation may be responsible for the high incidence of infection following severe head injury. The possible significance of increased monocyte phenotypic expression is discussed.
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PMID:Severe head injury: effect upon cellular immune function. 167 41

Infection is a common and serious complication of severe head injury. Immunocompetence in 25 severely head injured patients was investigated by measuring: (1) delayed-type hypersensitivity (DTH) skin test responses to common antigens; (2) phytohaemagglutinin (PHA) stimulated peripheral blood lymphocyte (PBL): blastogenesis, phenotype expression, and lymphokine production; (3) lymphokine-activated killer (LAK) cytotoxicity, antibody dependent cellular cytotoxicity (ADCC) and natural killer (NK) cytotoxicity; and (4) immunoglobulin and complement levels. The incidence of anergy to DTH skin testing was 100%. There was a decrease in PHA stimulated: PBL blastogenesis (p = 0.002), T-cell expression (p = 0.018), helper T-cell expression (p less than 0.001), interleukin-2 receptor expression (p less than 0.001), interleukin-2 production (p = 0.035) and gamma-interferon production (p less than 0.001). LAK cytotoxicity was depressed following incubation with IL-2 (p less than 0.001). There was no significant decrease in immunoglobulin levels and all acute phase reactants tested increased. The results of this study indicate that the cellular arm of immune response, including lymphocyte activation and cytokine production, is suppressed following severe head injury. The lack of enhancement in LAK cytotoxicity following incubation of PBLs with interleukin-2 suggests that factors other than decreased interleukin-2 production, such as the inherent lymphocyte dysfunction, other soluble mediators or suppressor cells, may be responsible for the reduction in cellular immunity observed following severe head injury.
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PMID:Humoral and cellular immunity following severe head injury: review and current investigations. 168 38

Natural killer cells are postulated to play an important role in host anti-viral defences. We measured natural killer cell activity in 30 individuals with acute measles (73 +/- 21 lytic units (LU)/10(7) cells) and 16 individuals with other infectious diseases (149 +/- 95 LU) and found it reduced compared with values for adults (375 +/- 70 LU; P less than 0.001) or children (300 +/- 73 LU, P less than 0.01) without infection. Reduced natural killer cell activity was found in measles patients with (84 +/- 30 LU) and without (55 +/- 18 LU) complications and was present for at least 3 weeks after the onset of the rash. Activity was increased by in vitro exposure of cells to interleukin-2. Depressed natural killer cell activity parallels in time the suppression of other parameters of cell-mediated immunity that occurs during measles.
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PMID:Natural killer cell activity during measles. 169 63

After infection with M. tuberculosis, about 5% of individuals develop progressive tuberculosis during the following two years and an additional 5% delayed reactivation. The genetic and acquired factors which place individuals at risk of tuberculosis are partly defined; however, the connection of the susceptibility to the host immune response is much less clear. Recent studies have examined the basis for the immunosuppression that is a concomitant of tuberculosis. Direct stimulation of monocytes primed during the course of tuberculous infection by mycobacterial peptides appears to be responsible for suppression of PPD-induced responses. Increased expression and release of interleukin-2 receptors and transforming growth-factor beta are associated with and may contribute to such suppression by monocytes. Additional studies have addressed the generation of immunity or immunosuppression. Ingestion of live M. tuberculosis by monocytes leads to selective expansion of gamma-delta T cells as opposed to CD4 lymphocytes. This may be relevant to the innate response to infection with M. tuberculosis as well as immunoregulatory circuits. Increased understanding of the basis for immunosuppression is of intrinsic interest as regards regulation of specific pathways of immune reactivity in an infectious disease of humans and may provide some insight into factors predisposing to tuberculosis.
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PMID:Regulation of the human cellular immune response to Mycobacterium tuberculosis. The mechanism of selective depression of the response to PPD. 175 94

Infection is a major complication of severe head injury, occurring in 50% to 75% of patients who survive to hospitalization. Previous investigations of immune activity following head injury have demonstrated suppression of helper T-cell activation. In this study, the in vitro production of interferon-gamma (INF-gamma), interleukin-1 (IL-1), and interleukin-2 (IL-2) was determined in 25 head-injured patients following incubation of peripheral blood lymphocytes (PBL's) with the lymphocyte mitogen phytohemagglutin (PHA). In order to elucidate the functional status of cellular cytotoxicity, lymphokine-activated killer (LAK) cell cytotoxicity assays were performed both prior to and following incubation of PBL's with IL-2 in five patients with severe head injury. The production of INF-gamma and IL-2 by PHA-stimulated PBL's was maximally depressed within 24 hours of injury (p less than 0.001 for INF-gamma, p = 0.035 for IL-2) and partially normalized within 21 days of injury. There was no change in the production of IL-1. When comparing the in vitro LAK cell cytotoxicity of PBL's from head-injured patients and normal subjects, there was a significant depression in LAK cell cytotoxicity both prior to (p = 0.010) and following (p less than 0.001) incubation of PBL's with IL-2. The results of this study indicate that IL-2 and INF-gamma production, normally required for inducing cell-mediated immunity, is suppressed following severe head injury. The failure of IL-2 to enhance LAK cell cytotoxicity suggest that factors other than decreased IL-2 production, such as inhibitory soluble mediators or suppressor lymphocytes, may be responsible for the reduction in cellular immune activity following severe head injury. These findings may have significant implications in designing clinical studies aimed at reducing the incidence of infection following severe head injury.
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PMID:Impairment of helper T-cell function and lymphokine-activated killer cytotoxicity following severe head injury. 183 15

Infection by human immunodeficiency virus type 1 (HIV-1) is associated with cellular activation and expression of the interleukin-2 (IL-2) receptor. A genetically engineered fusion toxin, DAB486 IL-2, that contains the enzymatic site and translocation domain of diphtheria toxin and the receptor binding domain of IL-2 specifically kills cells that express high-affinity IL-2 receptors. This toxin selectively eliminated the HIV-1-infected cells from mixed cultures of infected and uninfected cells and inhibited production of viral proteins and infectious virus. Thus, cellular activation antigens present a target for early antiviral intervention.
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PMID:Selective elimination of HIV-1-infected cells with an interleukin-2 receptor-specific cytotoxin. 190 28

The immunological mechanisms required to engender resistance have been defined in few infectious diseases of man, and the role of specific cytokines is unclear. Leprosy presents clinically as a spectrum in which resistance correlates with cell-mediated immunity to the pathogen. To assess in situ cytokine patterns, messenger RNA extracted from leprosy skin biopsy specimens was amplified by the polymerase chain reaction with 14 cytokine-specific primers. In lesions of the resistant form of the disease, messenger RNAs coding for interleukin-2 and interferon-gamma were most evident. In contrast, messenger RNAs for interleukin-4, interleukin-5, and interleukin-10 predominated in the multibacillary form. Thus, resistance and susceptibility were correlated with distinct patterns of cytokine production.
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PMID:Defining protective responses to pathogens: cytokine profiles in leprosy lesions. 155 22

Human herpesvirus-6 (HHV-6) is a recently identified T lymphotropic virus. We have examined the ability of HHV-6 to replicate in mature and immature human thymocytes. Infection of both cell populations revealed that only mitogen-activated mature thymocytes could support efficient virus replication. Because interleukin-2 (IL-2) plays a central role in T cell activation we investigated its effect on HHV-6 replication. Unexpectedly, addition of recombinant IL-2 at concentrations-exceeding 10 U/ml strongly inhibited the virus-induced cytopathic effect. Electron microscopic examinations and immunofluorescence assays revealed a threefold reduction in the fraction of infected cells, and almost total absence of extracellular virions in the IL-2-treated cultures. It will therefore be of interest to determine whether the IL-2-mediated inhibitory effect plays some role in the establishment of HHV-6 latency in the human host.
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PMID:Interleukin-2 inhibits the replication of human herpesvirus-6 in mature thymocytes. 215 89


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