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Does the epithelium play a central role in the immune function of rhinopharyngeal tonsils? An immunocytochemical and ultrastructural study.

Enlarged adenoids from 10 children with chronic rhinitis and otitis media with effusion have been studied immunocytochemically and ultrastructurally, to better define the possible role of the epithelium and the dendritic accessory cells in the immune activation of lymphoid cells, and provide further insight into the pathogenesis of the disease. The presence within the columnar epithelium of lymphocytes positive for CD8 antigen, and which electron microscopically have been found frequently apposed to degenerating epithelial cells suggests that the latter cells are targets for cytotoxic activity of intraepithelial lymphocytes, rather than being engaged in antigen presentation. Furthermore, the finding of typical dendritic accessory cells, recognized by their typical immunophenotypic and ultrastructural features, in the lamina propria, indicates that antigen presentation is more likely exerted by dendritic accessory cells. This is further supported by the fact that these cells express major histocompatibility (MHC) class II molecules, which are needed for antigen presentation, whereas epithelial cells do not. A possible relationship between epithelial damage and the pathogenesis of adenoidal enlargement is discussed.

Adenoids↗

Pituitary adenylate cyclase-activating polypeptide inhibits cutaneous immune function.

Epidermal nerves are closely associated with Langerhans cells (LC) and may be able to release factors, such as calcitonin gene-related peptide and epinephrine, that affect LC function. LC and the LC-like cell line XS106 express mRNA for the pituitary adenylate cyclase-activating polypeptide (PACAP) receptors VPAC1 and VPAC2. We examined whether PACAP regulates cutaneous immunity. Intradermal administration of PACAP prior to application of a contact sensitizer at the injected site inhibited the induction of contact hypersensitivity. Pretreatment of murine epidermal cells enriched for LC content (approximately 12% LC) with PACAP inhibited their ability to elicit delayed-type hypersensitivity in previously immunized mice. In vitro, PACAP suppressed the ability of both murine epidermal cells and highly purified LC (approximately 95%) to present antigen to a T cell clone and hybridoma. Furthermore, in LC and the XS106 cell line, PACAP inhibited the LPS/GM-CSF-induced stimulation of IL-1beta secretion and augmented IL-10 production. PACAP also down-regulated CD86 expression in LPS/GM-CSF-stimulated XS106 cells. The immunosuppressive effects of PACAP may be due to modulation of cytokine production and CD86 expression.

Animals↗

Bioinformatic strategies for better understanding of immune function.

Novartis Foundation sponsored a Symposium which brought together a group of experimental immunologists, theoretical immunologists, and bioinformaticians to discuss the new field of immunoinformatics. The discussion focused on immunological databases, antigen processing and presentation, immunogenomics, host-pathogen interactions, and mathematical modelling of the immune system. A main conclusion of the meeting is the critical role played by immunoinformatics in current immunology research. In particular, immunoinformatics provides a foundation for the emerging fields of systems immunology and immunogenomics.

Allergy and Immunology↗

Modulation of immune function by UV radiation.

In addition to its carcinogenic activity, ultraviolet (UV) radiation is capable of modifying certain immunologic reactions. Immunologic alterations induced in mice by UV radiation include both local and distant effects. Local alterations result from a direct effect of UV radiation on an immune reaction that takes place at the site of irradiation. Distant alterations are those in which exposure of skin to UV radiation at one site modifies an immune reaction occurring at a distant, unexposed site. Based on recent studies, we propose that there may be two types of distant alterations. One is nonspecific, may be due to accumulation of leukocytes at the site of UV-induced inflammation, and is exemplified by the suppression of delayed hypersensitivity and local graft-versus-host (GVH) reactions. The second may result from DNA damage, may involve a soluble mediator, and is manifested by the systemic suppression of contact hypersensitivity and the formation of antigen-specific suppressor T lymphocytes. These immunologic effects of exposure to UV radiation may be important in the pathogenesis of skin cancer and other cutaneous diseases.

Animals↗

Immune function, mutant frequency, and cancer risk in the DNA repair defective genodermatoses xeroderma pigmentosum, Cockayne's syndrome, and trichothiodystrophy.

There is evidence for defective DNA repair in xeroderma pigmentosum, Cockayne's syndrome, and trichothiodystrophy, but for increased cancer risk only in xeroderma pigmentosum. Natural and adaptive immune surveillance and mutant frequency to 6-thioguanine resistance in circulating T-lymphocytes were studied in five patients with xeroderma pigmentosum, two with Cockayne's syndrome, and one with trichothiodystrophy. Forty-eight-hour cutaneous hypersensitivity responses to recall antigens excluded anergy and circulating CD3+, CD4+, CD8+, and CD16+ cell numbers were within normal limits in all patients tested, as were proliferative lymphocyte responses to PHA, except in the trichothiodystrophy patient. Proliferative responses to recall antigens (PPD, SKSD, and Candida) showed that all patients responded to one or more antigens. Direct natural killer cytotoxicity measured against the human erythromyeloid leukaemia cell line K562 using a 4-h 51Cr release assay was significantly reduced in xeroderma pigmentosum (specific cytotoxicity less than mean +/- SD greater than 17.4 +/- 9.4 per cent, with effector:target cell ratio of 50:1) compared to normal controls (45.8 +/- 17.8), but normal in Cockayne's syndrome and trichothiodystrophy. Generation of lymphokine activated killer cell activity was normal in the two xeroderma pigmentosum lines tested. The mutant frequency in the xeroderma pigmentosum donors was significantly increased (p less than 0.01) and was elevated in the two Cockayne's syndrome donors, taking age into account. No mutants were observed from the single trichothiodystrophy donor. These findings suggest that reduced natural killer cell activity may contribute to the greatly increased susceptibility to skin cancer in xeroderma pigmentosum.

Antigens, CD↗

[Comparison of the effect of sijunzi decoction, siwu decoction and bazhen decoction on immune function in mice].

Sijunzi decoction, Siwu decoction and Bazhen decoction can antagonize the suppressive effect of hydrocortisone on proliferation of lymphocyte by spleen cells in C57BL/6J mice in vitro, and of the three decoctions Sijunzi works best. Sijunzi Decoction can antagonize the suppressive effect of cyclophosphamide on the delayed cutaneous hypersensitivity (DCH) induced by DNCB in mice and the production of hemolysin in mice immunized with SRBC. The three prescriptions all can enhance the clearance rate of iv charcoal particles as well as bone marrow cells inhibited by cyclophosphamide in mice, but Sijunzi decoction functions best of all.

Adjuvants, Immunologic↗

Flt3 ligand: role in control of hematopoietic and immune functions of the bone marrow.

The concerted action of cytokines secreted locally in the bone marrow controls the maintenance, expansion, and differentiation of hematopoietic stem cells (HSCs), whereas aberrant cytokine signaling contributes to leukemic transformation. Potent effects of flt3 ligand on HSCs and the development of the immune system have generated much interest in the clinical application of this cytokine in stem cell transplantation and cancer immunotherapy.

Animals↗

Effects of intravenous silica on immune and non-immune functions of the murine host.

Silica, an agent toxic for macrophages, administered i.v. to DBA/2 mice rapidly depresses the clearance of colloidal carbon by the reticuloendothelial system and reduces the in vitro phagocytic activity of peritoneal macrophages harvested 3 days after silica injection. Silica blocks the humoral immune response to sheep erythrocytes and the cell-mediated immune response to allogeneic fibroblasts when given before antigen. Silica also induces complex alterations in spleen cell responsiveness to concanavalin A involving both local and serum factors. Silica had no significant effect on the induction of interferon by statolon or Newcastle disease virus. No unequivocal evidence was obtained that silica has a direct depressive effect on cells other that macrophages, but indirect effects on lymphocytes were produced most likely by factors released from silica-lysed macrophages. Intravenous silica may prove useful for the separation of interferon induction and immune response stimulation in studies of host resistance to infection and oncogenesis. Considerable variation exists in the immunodepressive effects of different preparations of silica.

Animals↗

Multiple Fusobacterium nucleatum liver abscesses. Association with a persistent abnormality in humoral immune function.

A previously healthy 29-year-old man developed multiple hepatic abscesses secondary to Fusobacterium nucleatum. No underlying local disease was found. The leading portal of entry for the bacterium may have been the oral cavity; 4 days before the onset of his illness he had had extensive dental work. Immunological evaluation during the illness and in late convalescence (16 weeks after onset) revealed a persistent B cell abnormality characterized by markedly depressed in vitro secretion of immunoglobulins in response to pokeweed mitogen; however, serum immunoglobulins and IgG subclasses were normal. Abnormal numbers of suppressor T cells (OKT8+) and increased suppressor function were also present. Anaerobic pyogenic liver abscesses may occur in the absence of obvious underlying disease, but this case suggests that there may be an association with in vitro abnormalities of the immune system.

Adult↗