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Prognostic significance of cellular immunity to autologous breast carcinoma and glycoprotein 55.

Using a skin window (SW) procedure, we evaluated post-operative cell-mediated immunity (CMI) to autologous breast cancer with reference to its prognostic significance, the nature of the immunogen, and the therapeutic implications. It appears that SW reactivity to autologous breast cancer is prognostically favorable per se and is independent of the prognostic significance of the nuclear grade of the cancer cells; SW reactivity to autologous breast cancer reflects CMI to a determinant(s) that is expressed by glycoprotein 55, the principal envelope glycoprotein of the RIII-murine mammary tumor virus; the glycoprotein 55-like CMi determinant(s) is more regularly expressed by preinvasive than by invasive breast cancers; tumor antigenicity and host reactivity may vary independently; and postoperative monitoring of CMI to autologous breast cancer is prognostically and therapeutically important.

Breast Neoplasms↗

The role of cyclic adenosine monophosphate in the suppression of cellular immunity after thermal injury.

BACKGROUND AND OBJECTIVE: Cyclic adenosine monophosphate (cAMP) is an intracellular second messenger that is known to convey inhibitory signals for T-cell proliferation and function. We investigated the association between this molecule and the profound immunosuppression that accompanies thermal injury. DESIGN: Mice were randomized into two groups: one group was subjected to a 20% full-thickness scald burn; the second to a sham burn (control). The mice were killed on days 4, 7, or 10 after the burn injury and splenocytes were pooled and cultured for 15 minutes in the presence or absence of prostaglandin E2 (PGE2). RESULTS: Levels of cAMP in splenocytes were significantly elevated on day 7 after burn in the burn group compared with the sham controls (P < .05, Wilcoxon Rank Sum Test). Incubation of splenocytes with PGE2 resulted in significantly greater levels of intracellular cAMP in cells from the burn group compared with controls on days 4, 7, and 10. Incubation of normal splenocytes with dibutyryl cAMP in the presence of concanavalin A significantly decreased cell proliferation and the production of interleukin-2. The decrease in interleukin-2 production was evident at the level of messenger RNA expression. Stimulation of splenocytes with a combination of phorbol ester and calcium ionophore, bypassing all membrane-associated events prior to protein kinase C activation, reversed the inhibitory effects of dibutyryl cAMP. Incubation of splenocytes from burned animals with H-8, a selective inhibitor of cAMP-dependent protein kinases, restored the proliferative response to that of sham controls on days 4, 7, and 10 after thermal injury. CONCLUSIONS: These data indicate that elevated levels of intracellular cAMP, combined with an increased production of cAMP in response to circulating PGE2, may play a fundamental role in suppression of the immune response following thermal injury and that cAMP exerts its immunomodulatory effects prior to protein kinase C activation.

Animals↗

Humoral and cellular immune responses in asthmatic isocyanate workers: report of two cases.

Two workers (23 and 28 years old) developed rhinitis and bronchial asthma after occupational contact with the isocyanate MDI. Positive skin prick test results for MDI-HSA and IgE antibodies to all isocyanate-HSA conjugates were obtained in both cases, and the inhalation challenge test with MDI produced immediate and late asthmatic reactions. In the patch test and the stimulation assay of peripheral mononuclear blood cells, a specific sensitization to the diamine MDA (in both cases) and to further amines (in one case), as well as to hydrolysates of the respective diisocyanates, was seen, which appears to be independent of the IgE response to isocyanate-HSA conjugates. Our results offer evidence of IgE-mediated, as well as lymphocyte, responses induced by exposures to isocyanate products over several months or years.

Adult↗

Nickel release from orthodontic arch wires and cellular immune response to various nickel concentrations.

AIMS: Results from two previous clinical studies suggested that exposure to high nickel-containing orthodontic arch wires may induce hypersensitivity in certain individuals. The purpose of this study was to measure the amount of nickel released from three types of nickel-containing arch wires into a synthetic saliva in vitro, and determine if the concentrations were sufficient to elicit either cytotoxic (trypan blue exclusion test) or stimulatory (MTT test) responses in human peripheral blood mononuclear cells (PBMCs) derived from nickel-sensitive and nickel-nonsensitive individuals. PBMCs were exposed to five concentrations of nickel sulfate solutions ranging from 0-29 ppm, and results were compared, particularly at concentrations obtained from nickel release experiments. FINDINGS: The amount of nickel released into synthetic saliva ranged from 0.4-4.1 ppb. Wires subjected to a combination of soaking and cyclic straining released significantly more nickel than those that were soaked only (p </= 0.05), and NiTi wires released significantly more nickel than did stainless steel or nitrogen-implanted NiTi wires (p </= 0.05). For PBMCs, significant increased cell proliferation was not observed for any nickel concentration. PBMC cell death rates were highest at nickel concentrations of 29 ppm when the cells were cultured without a cell growth promoter (p </= 0.05), and MTT test values were significantly reduced at both 2.9 and 29 ppm when a growth promoter was included (p </= 0.05). CONCLUSION: The maximum amount of nickel released from all tested arch wires was 700 times lower than the concentrations necessary to elicit cytotoxic reactions in human PBMCs.

Adult↗

Quantitation of T and B lymphocytes and cellular immune function in Hodgkin's disease.

Peripheral blood T and B lymphocytes were quantitated in 42 patients with untreated Hodgkin's disease and the results compared with the response to phytohemagglutinin (PHA) stimulation and delayed hypersensitivity skin testing. T lymphocytes were identified by an in vitro cytotoxicity assay employing a specific anti-T-cell serum and by spontaneous rosette formation with sheep erythrocytes (E rosettes). The percentage of T cells in the patients was similar to that of normal subjects as judged by the cytotoxicity assay (65 to 90%). In addition, absolute T-lymphocyte counts were normal in 63% of the patients and were generally reduced only in those with lymphopenia. The percentage of T lymphocytes determined by the E-rosette assay was similar to that determined by the cytotoxicity assay in normal controls, but was significantly lower than that determined by the cytotoxicity assay in the patients. Moreover, the decreased response to PHA stimulation in the patients was directly correlated with the decrease in E-rosette formation. These findings suggest that T lymphocytes in the peripheral blood are not generally diminished in untreated Hodgkin's disease. However, a proportion of these cells exhibits altered surface interactions that may account for some aspects of their impaired immunologic function.

B-Lymphocytes↗

Cellular immunity to herpes simplex virus in man. VII. K-cell activity to HSV1 infected target cells in disease.

Herpes simplex virus-infected target cells, sensitised with antiviral antibody can be lysed by non-immune human lymphocytes (K-cells). This antibody dependent cell mediated immunity (ADCC) is a very efficient technique for destroying foreign target cells and may play a role in maintaining the localization of recurrent herpetic infections. We have used 51Cr labelled herpes virus infected target cells to examine the K-cell activity of peripheral blood lymphocytes in patients who have either malignant reticuloendothelial diseases or who are receiving cytotoxic and steroid therapy for other reasons. K-cell activity was generally within the normal range in such patients and was surprisingly stable despite the occasional use of relatively large doses of cytotoxic agents. It is unlikely, therefore, that a defect in ADCC is responsible for the dissemination of herpes virus infections that may be seen in association with the above drugs and diseases.

Antibodies, Viral↗

Effects of radiochemotherapy and splenectomy on cellular immunity in long-term survivors of Hodgkin's disease and non-Hodgkin's lymphoma.

Thirty-six patients treated for Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) who had been in complete remission and off all therapy for greater than two years were examined for evidence of immunosuppression. All patients were found to have marked depression of their lymphocyte blastogenic response to phytohemagglutinin (PHA) and of their skin test responses. No abnormalities of serum protein or immunoglobulins were found. T cells were significantly lower than normal in patients who had had Hodgkin's disease, but not in those who had had NHL. B cells, on the other hand, were significantly elevated in both groups. Splenectomy elevated the total lymphocyte count, while those who had not had a splenectomy had lower than normal lymphocyte counts. B cells were elevated while T cells tended to be lower in both splenectomy and nonsplenectomy groups, though only in the nonsplenectomized patients did this reach statistical significance. PHA response tended to be higher in patients with less advanced disease and less extensive treatment than in those with more advanced disease and more extensive treatment, although there was no statistically significant difference. Skin test response though, was shown to correlate well with both stage of disease at diagnosis and extent of treatment.

Adult↗

Cellular immunity in Hodgkin's disease.

Defective cell-mediated immunity (CMI) occurs early in the course of Hodgkin's disease (HD) and may persist even two years after successful treatment. This has been confirmed by in vivo and in vitro tests performed on 51 untreated and 52 treated patients of HD. The grading of skin reponse in vivo to dinitrochlorobenzene (DNCB) correlated very well with the in vitro leukocyte migration inhibition (LMI) response against phytohemagglutinin (PHA). An inhibitory influence of HD patients' sera was demonstrated by LMI tests in vitro. The response of peripheral leukocytes from HD patients in the LMI tests could be augmented in vitro by addition of levamisole (an immuno-potentiator) to the culture medium, thus pointing to an intrinsic defect in Lymphocytes. The data indicate that defect at multiple sites in the immune system is responsible for persistent anergy in HD.

Cell Migration Inhibition↗

Changes in cellular immunity among workers occupationally exposed to styrene in a plastics lamination plant.

BACKGROUND: Styrene is a widely used industrial chemical. Immune and hematological parameters were examined in 29 hand laminators and sprayers exposed to styrene for an average of 14 years and in 19 in-factory unexposed controls. The workers performed hand lamination procedures in a production area with an average area airborne styrene level of 139.5 mg/m(3). Mean concentration of styrene in the blood of exposed workers was 945.7 microg/L and the mean styrene in exhaled air was 38.8 microg/L. METHODS: Parameters of internal and external exposure, immune function assays, immunoglobulins, acute phase reactants and hematology were evaluated in exposed and non-exposed populations. RESULTS: Using multifactorial analysis of variance we found a significant decrease in proliferation of lymphocytes stimulated by Concanavalin A but not by pokeweed mitogen (PWM) in workers occupationally exposed to styrene. Proliferative response to PWM was significantly correlated with the levels of styrene in blood. Phagocytic activity of monocytes, levels of IgG, IgA, IgM, IgE and alpha-2-macroglobulin in serum were indistinguishable in the two groups. The population exposed to styrene had increased levels of C4-component of complement. Levels of C3-component of complement were positively correlated with duration of exposure. A significant elevation in the percentage and number of monocytes and a significantly decreased number of lymphocytes were seen in exposed workers. Styrene concentrations in both blood and exhaled air were associated with decreased percentage of large granular lymphocytes. CONCLUSIONS: These results suggest immune alterations of cell-mediated immune response of T-lymphocytes and imbalance in leucocyte subsets in peripheral blood of workers exposed to styrene.

Acute-Phase Proteins↗

Cellular immune response to measles, mumps, and vaccinia viruses in multiple sclerosis.

The cell-mediated immune response to measles, mumps, and vaccinia viruses was studied in MS patients, normal controls, and neurological disease controls using a lymphocyte proliferation assay. A small but significant difference was found in the response to measles between the MS and normal control groups but not between the MS and neurological disease control groups. In each of the groups, the response of both peripheral blood leukocytes and purified T-cells to measles was significantly less than the response to mumps or vaccinia. The lower response to measles was not due to the presence of blocking factors or to lack of antigenicity of the measles virus preparation used in the assay. These findings suggest that differences exist in the normal immune response between these viruses. Precise quantitation of the immunological response to viruses in MS and other disease states will depend on identification of the various functionally reactive cell populations.

Adult↗

Polydnavirus of Campoletis chlorideae: characterization and temporal effect on host Helicoverpa armigera cellular immune response.

Polydnavirus was isolated from oviduct calyx in the parasitoid wasp Campoletis chlorideae (Hymenoptera: Ichneumonidae), and termed CcIV. The virus particles consist of fusiform nucleocapsids surrounded by two unit membrane envelopes. The DNAs purified from these viruses were found diversified in molecular weight and existed in nonequimolar concentrations. At least 20 different-sized bands were present after electrophoresis, and they ranged from approximately 3 to 26 kb. Persistence and gene expression of CcIV were examined in parasitized and virus-injected Helicoverpa armigera larvae. Viral DNA could be detected in the hemocyte of H. armigera at 30 min post-parasitization (p.p.), and persisted for 6 days. While no viral DNA increase was found, CcIV transcripts were first detected in host hemocytes at day 1 p.p. and continued for 5 days. Similar transcripts were observed in hemocytes from larvae that had been injected with calyx fluid or CcIV 24 h earlier. CcIV viral DNAs hybridized only with certain first-strand cDNAs from hemocytes, suggesting that only part of the CcIV genome was expressed in H. armigera. The pattern of CcIV gene expression was consistent with that of the inhibition of encapsulation for Sephadex G-10 and parasitoid eggs by host larvae. The recovery of host immune response at day 4 p.p. indicated that CcIV exhibited a partial and temporal effect on the host immune system and the developing parasitoid appeared to avoid encapsulation via different mechanisms.

Animals↗