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

Infection by the human T-cell lymphotropic virus type I (HTLV-I) causes T-cell activation by at least two separate mechanisms. One mechanism involves activation of the T cells harboring the virus and is exemplified by in vivo infected nonimmortalized T-cell clones that display a prolonged state of activation. This HTLV-I-induced T-cell activation is inhibited by rapamycin, a drug that inhibits p70 S6-kinase and blocks cell cycle in G1, but is not inhibited by FK506 or cyclosporin A, both of which inhibit interleukin-2 (IL-2) production. The phenotype of this pathway is consistent with an hyperactive IL-2R pathway or CD28 pathway, indicating that HTLV-I may contribute a costimulatory signal to the infected T cell. As a separate mechanism, HTLV-I-infected T cells can induce activation of uninfected T cells via T-T-cell interaction mediated by the LFA-3-CD2 pathway. This may induce IL-2 production from the uninfected T cells, leading to a more generalized activation of the immune system that potentially could provide a basis for some of the diseases associated with HTLV-I. Moreover, this THTLV-I-T-cell interaction could explain the spontaneous proliferation observed in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis.
 ...
PMID:HTLV-I-induced T-cell activation. 879 12

Although in vitro systems have provided important information about the composition and nature of various immune responses, understanding physiologically relevant function and regulation requires evaluating in vivo conditions. Two different models of acute viral infections have made possible the characterization of a variety of responses to these agents, including natural killer (NK) cell activation and regulation during infection; these are mouse infections with lymphocytic choriomeningitis virus (LCMV) and murine cytomegalovirus (MCMV). The results of our characterization of the NK cell responses elicited in these models and the methods used to dissect the regulation of these responses are reviewed here. Cytotoxicity, proliferation, and cytokine expression assays as well as flow cytometric analyses are used to characterize the in vivo responses. Both of the infections induce early NK cell cytotoxicity and blastogenesis. Infection with MCMV but not LCMV also induces NK cell production of the antiviral cytokine, interferon-gamma (IFN-gamma). Antibodies, to mediate in vivo cell subset depletion or cytokine neutralization, and mice, genetically altered to have cell subset or cytokine deficiencies, are utilized to identify the regulatory pathways and mechanisms controlling endogenous NK cell responses to the infections. The major mediators of the regulation of NK cell function during viral infection of normal mice are IFN-alpha/beta and interleukin-12 but not interleukin-2. Furthermore, the induction of later T-cell responses contributes to the negative regulation of NK cells by promoting the production of inhibitory factors including biologically active transforming growth factors-beta. Thus, the study of immune responses to viral infections has provided and will continue to provide important insights into the characteristics of endogenous NK cell responses and the cells and factors that regulate these responses in vivo.
 ...
PMID:Function and Regulation of Natural Killer (NK) Cells during Viral Infections: Characterization of Responses in Vivo 881 91

We prepared a recombinant retroviral vector expressing the human T-lymphotropic virus type-I tax gene. Infection of WKA/H rat splenocytes yielded T-cell lines which proliferated continuously in media supplemented with exogenous interleukin-2 (IL-2) after the control cells ceased to grow. The phenotype of these cells closely resembled that of typical adult T-cell leukemia cells and tax-immortalized human T cells; i.e., positive for CD3, CD4 and IL-2 receptor alpha-chain. Chromosomal analysis revealed that about 10% of the tax-transduced T cells had several chromosomal abnormalities. We also performed in vivo characterization of tax-transduced splenocytes by injecting them into newborn syngeneic rats soon after in vitro infection. Maintenance of the injected tax-transduced cell population and in vivo expression of the tax gene was confirmed in the splenocytes of the injected rats by polymerase chain reaction. However, development of obvious disease was not observed in these rats for up to 18 months after inoculation. These results indicate that tax is capable of immortalizing rat mature CD4+ T cells in vitro but may be insufficient for full transformation of these cells in vivo. Our in vivo system using retrovirally tax-transduced rat T cells could facilitate investigation of the additional genetic events that cooperatively transform T cells transduced with tax gene.
 ...
PMID:Rat primary T cells expressing HTLV-I tax gene transduced by a retroviral vector: in vitro and in vivo characterization. 889 48

The consequences of complexing an antigen with specific antibodies upon the antigen-induced immune response were studied with respect to secretion of interleukin-2 (IL2), interleukin-6 (IL6), interleukin-10 (IL10) and interferon-gamma (IFN gamma). We found that the tetanus toxoid antigen-induced cytokine pattern was mainly dependent on the antigen/antibody ratio. While tetanus toxoid antigen alone induced a typical Th1-like cytokine pattern with high levels of IL2 and IFN gamma, equivalent or antibody-excess immune complexes induced a marked secretion of IL6 and IL10 while failing to induce IL2 and IFN gamma secretion. As the cytokine pattern plays a crucial role in the development of specific immune responses towards infectious agents, our results indicate that immune complexes--typically occurring during the course of chronic infectious diseases--may play an important role in the modulation of immune responses. Since a shift from Th1 to Th2 immune responses has been discussed as a pathogenetic factor in HIV-induced immunodeficiency, the role of circulating immune complexes as a possible cause for this shift should be considered.
 ...
PMID:Distinct antigen-induced cytokine pattern upon stimulation with antibody-complexed antigen consistent with a Th1-->Th2-shift. 890 28

Onchocerciasis is a chronic infectious disease caused by the filarial nematode Onchocerca volvulus. A minor population of human gammadelta T cells expressing Vdelta1 chains is preferentially stimulated by O. volvulus ligands in vitro. Therefore, the nature of the parasite ligand and the effector functions of Vdelta1+ T cells stimulated by O. volvulus was investigated. A 5- to 30-kDa ligand from the adult parasite lysate that is sensitive to proteinase treatment was identified. Presentation for preferential stimulation of Vdelta1+ T cells required processing. After in vitro stimulation with O. volvulus in the presence of interleukin-2, Vdelta1+ T cells produced interferon-gamma but not interleukin-4 and exhibited NK cytolytic activities. It is concluded that somatic 5- to 30-kDa protein ligands from O. volvulus stimulate Vdelta1+ T cells and that Vdelta1+ T cells play a role in immunity to O. volvulus.
 ...
PMID:Low-molecular-weight protein ligands from Onchocerca volvulus preferentially stimulate the human gammadelta T cell Vdelta1+ subset. 894 Feb 23

The effects of physical therapy on immunological parameters were evaluated in 22 patients (14 males, aged 68.1 +/- 9.9 years) with cerebrovascular diseases in a stable situation 3 to 6 months after the onset of stroke who were entered into a rehabilitation program in our hospital between 1990 and 1993. The proportion of CD4+ cells was significantly increased but that of CD8+ cells was decreased throughout the rehabilitation program, resulting in an increase in the ratio of CD4+/CD8+ cells. The lymphocyte response to phytohemagglutinin and concanavalin A was increased, while no significant differences were observed in CD3+ cells, natural killer cell activity, and serum levels of immunoglobulins, interleukin-1 beta, interleukin-2 and interleukin-6. These findings suggest that repeated physical exercise may activate the immune system, especially T-cell function, for possible prevention of infectious diseases that are often complicated in patients with cerebrovascular diseases.
 ...
PMID:Effects of physical therapy on immunological parameters in patients with cerebrovascular diseases. 898 64

Toxoplasma gondii is an obligate intracellular parasitic protozoan that infects a variety of warm-blooded animals, including humans. Infection is usually asymptomatic in immunocompetent individuals but may be devastating in immunocompromised individuals such as those with acquired immunodeficiency syndrome (AIDS). Clinical manifestations of infection in immunocompromised patients include the development of encephalitis. It has been estimated that approximately 30% of patients with AIDS who are latently infected will eventually develop toxoplasmic encephalitis. The most common regimen used to treat toxoplasmic encephalitis is a combination of pyrimethamine 50 to 100 mg/d and sulfadiazine 4 to 8 g/d, with or without folinic acid 10 mg/d. This regimen, however, commonly leads to adverse effects or relapses. Other pharmacologic approaches include the use of clindamycin rather than sulfadiazine, the macrolide antibiotics, atovaquone, 5-fluorouracil, trimethoprim/sulfamethoxazole, minocycline or doxycycline, trimetrexate with folinic acid, dapsone, rifabutin, pentamidine, and diclazuril. None of these alternative regimens has been proven to be more effective than the standard pharmacologic therapy. An evolving approach is the use of immunotherapy, such as interleukin-2, -6, and -12; interferon-gamma; and alpha-tumor necrosis factor. Restoring a competent immune system may be the only cure for toxoplasmosis and other opportunistic infections.
 ...
PMID:Treatment regimens for patients with toxoplasmic encephalitis. 900 22

Human immunodeficiency virus-type 1 (HIV-1) infection is characterized by a chronic state of immune hyperactivation in patients. Infection of human peripheral blood lymphocytes with HIV-1 in vitro resulted in increased interleukin-2 (IL-2) secretion in response to T cell activation via the CD3 and CD28 receptors. Expression of the HIV-1 transactivator Tat recapitulated this phenotype and was associated with increased IL-2 secretion in response to costimulation with CD3 plus CD28. IL-2 superinduction by Tat occurred at the transcriptional level, was mediated by the CD28-responsive element in the IL-2 promoter, and was exclusively dependent on the 29 amino acids encoded by the second exon of Tat.
 ...
PMID:Immune hyperactivation of HIV-1-infected T cells mediated by Tat and the CD28 pathway. 904 14

Stimulation of T-lymphocytes with mitogens or antigens results in the production of the cytokine interleukin-2, which exerts its physiological effect by interacting with a specific IL-2 receptor on the cell surface. The alpha-chain of this receptor is induced and expressed on the cell surface after lymphocyte activation. Following continuous antigen stimulation, a smaller soluble form of this alpha-subunit (sIL-2R-alpha) is shed from the membrane of activated cells. This study describes a sandwich ELISA for bovine sIL-2R-alpha that was developed using monoclonal antibodies specific for bovine IL-2R-alpha (CD 25). The feasibility of using sIL-2R-alpha released by activated T-lymphocytes as an in vitro marker of cell-mediated immunity (CMI) in cattle is demonstrated. Calves were immunized with the foreign protein keyhole limpet haemocyanin (KLH) and the development of CMI was followed using sIL-2R-alpha release, IFN-gamma production and lymphocyte proliferation assay. The results showed that the release of sIL-2R-alpha by previously sensitized cells following stimulation with antigen is likely to be a useful marker of CMI in infectious diseases, and in the study of T cell antigens and/or novel vaccines. Using appropriate detection systems, the measurement of sIL-2R-alpha may also prove to be a useful marker of CMI in other species.
 ...
PMID:Development of a sandwich immunoassay for the detection of soluble bovine interleukin-2 receptor-alpha (sIL-2R-alpha) and its use to measure cell-mediated immunity in cattle. 906 Jan 39

Distinct cytokine profiles are clearly associated with and relate to the severity of several types of infections. Cytokine networks are apparent with selected human infectious diseases, such as mycobacterial infections (leprosy, tuberculosis), the parasitic infection leishmaniasis, human immunodeficiency virus (HIV) infection, and gram-negative sepsis. Cytokine profiles are determined to some extent by two functional subsets of T lymphocytes, Th1 and Th2. The Th1 cytokines (interferon gamma, interleukin-2 [IL-2], IL-12) enhance cell-mediated immunity, inhibit humoral immunity, and result in protective effect for pathogens that are removed primarily through cell-mediated immunity (Mycobacterium tuberculosis, Mycobacterium leprae, Leishmania). The Th2 cytokines (IL-4, IL-5, IL-10, IL-13) enhance humoral immunity and inhibit cell-mediated immunity, and result in protective effect for pathogens removed primarily through humoral mechanisms. Progression of HIV infection is associated with a switch from a Th1 to a Th2 profile. For sepsis, uncontrolled activation of proinflammatory cytokines (IL-1, tumor necrosis factor-alpha, interferon-gamma) may be a fundamental defect that promotes the detrimental aspects of inflammation, whereas Th2 cytokines may be beneficial in controlling inflammation. Knowledge of basic cytokine immunopharmacology, networks, and relationships with infectious processes will aid clinicians in determining treatment approaches that are likely to be effective.
 ...
PMID:Cytokine networks with infection: mycobacterial infections, leishmaniasis, human immunodeficiency virus infection, and sepsis. 908 11


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>