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Expression of human complement receptor 2 (CR2, CD21) in Cr2-/- mice restores humoral immune function.

Complement receptor type 2 (CR2, CD21) is expressed by both human and murine B cells and has been demonstrated to play a pivotal role in the humoral immune response. We have reconstituted Cr2-/- mice with an 80-kb human genomic fragment (designated P1-5) containing the full-length human CR2 (hCR2) gene. Transfection of P1-5 into the mouse A20 B cell line confirmed that it would direct expression of the hCR2 protein in mouse B cells. Immunoprecipitation analysis in these cells revealed that hCR2 coassociates with mouse CD19. After creation of transgenic mice using P1-5, we found significant expression of hCR2 on peripheral blood and splenic B cells by flow cytometric analysis. RT-PCR analysis of tissues and purified cell populations from transgene-positive mice revealed that hCR2 expression was restricted to B cells and the spleen in a pattern that matches mouse CR2. To rigorously assess the functional capabilities of hCR2, the transgene was bred onto Cr2-/- mice, which have a notable defect in response to SRBC Ag. We found that Cr2-/- mice expressing hCR2 had a substantial restoration of the humoral immune response to SRBC as compared with nontransgenic Cr2-/- littermate controls. Overall, this study suggests that hCR2 is able to substitute for mouse CR2 in the murine immune system. Therefore, hCR2-transgenic mice offer a valuable model system to further examine immunologic roles as well as structure-function relationships important for hCR2 function in primary cells in vivo.

Animals↗

Effects of subchronic exposure to diethylstilbestrol on humoral immune function in adult female (C3B6)F1 mice.

Adult female (C57BL/6 X C3H)F1 (B6C3F1) mice were treated with diethylstilbestrol for 14 days and assayed for the ability to produce antibody to a T-dependent antigen, a T-independent antigen, and to respond in vitro to stimulation by a polyclonal activator, bacterial lipopolysaccharide (LPS). No suppression of the in vivo antibody responses were observed. DES produced a subtle alteration in the response to the T-dependent antigen, sheep erythrocyte (sRBC), as treated groups maintained higher PFC values than vehicle groups after the peak day of the response. DES induced an enhanced response to the T-independent antigen, DNP-Ficoll. Spleen cells from DES-exposed animals were only marginally altered in their ability to produce antibody in vitro in response to LPS. Parallel experiments indicated a comparable reduction of LPS-induced blastogenesis. Serum immunoglobulin levels were determined following DES exposure, as a measure of baseline immunocompetence. DES only caused a reduction in the immunoglobulin M (IgM) isotype. DES exposure caused a significant enhancement of the activity of the reticuloendothelial (RES) system. Experiments were performed to assess the effects of enhanced RES function on concentrations of 51Cr labeled sRBC, which were optimal for antibody production. When sRBC were administered i.p., there was no effect on either the Ab response (as reported above) or on the number of sRBC localized in the spleen. In contrast, when sRBC were administered i.v., exposure to DES reduced (approximately 50%) both the Ab response and the number of sRBC localized in the spleen. Enhanced phagocytic function and alterations in antigen distribution must be considered in the interpretation of in vivo immune responses.

Animals↗

Immune function of thyroid stimulating hormone and receptor.

Thyroid stimulating hormone (TSH) is a central component of the hypothalamus-pituitary-thyroid axis. Although TSH is known for its important biological effects as a neuroendocrine used to regulate thyroid hormone activity and subsequent metabolic functions, TSH also has been shown to be produced and used by cells ofthe mammalian immune system. Moreover, recent findings have linked the use of TSH by cells of the immune system in humans and mice to a group of monocytic cells and lymphocytes--primarily dendritic cells, macrophages, and subset of naïve peripheral T cells. Other studies have demonstrated the capacity of dendritic cells and monocytes to produce biologically active TSH, thereby pointing to a process of paracrine or autocrine TSH-mediated communication during the earliest stages of an immune response to antigen. In this article, these and other features of TSH immune-endocrine interactions are discussed in the context of an intrinsic TSH immunological pathway. Additionally, a hypothesis is proposed in which TSH produced by cells of the immune system during acute antigen exposure plays a dual role, consisting on the one hand of TSH communication during antigen-driven immune activation while concomitantly serving to regulate physiological homeostasis by modulating and adjusting thyroid hormone activity.

Animals↗

PHA-stimulated cellular immune function and T-lymphocyte subsets in major depressive disorders.

We measured some immunological parameters in 20 hospitalized patients with major depression and 20 age- and sex-matched healthy controls. Both enumeration of immune cells, including T-lymphocyte subpopulations, and assay of T-cell function were studied. White blood cells were evaluated with an automated cell counter, T-cell subsets with an immunobead technique, and T-cell function with a phytohemagglutinin-induced proliferation in vitro assay. We found that T-lymphocyte responses to the mitogen were significantly lower in depressed patients than in controls. All the other parameters were normal. These findings suggest that functional but not numerical changes in T-lymphocytes characterize major depressive disorders.

Adult↗

Immune functions in healthy blood donors with HLA-DW2 and -DW3 antigens.

We compared healthy blood donors with and without HLA-Dw2 and -Dw3 in immunity assays, the results of which have been found to be abnormal in multiple sclerosis or autoimmune diseases. Tests included lymphocyte blast transformation responses to rubella, mumps and purified tuberculin (PPD), in vitro production of IgG and interferons, natural killer (NK) cell function and measurement of serum antibodies to measles, rubella, mumps and herpes simplex viruses. HLA-Dw2-positive subjects had a lower lymphocyte blast transformation response to rubella virus antigen and a lower NK cell function compared with HLA-Dw2-negative subjects. The presence of HLA-Dw3 was associated with an increased spontaneous and mumps virus-induced immunoglobulin production. No significant differences were found in other assays. These results support the existence of HLA-Dw2- and Dw3-associated deviation of immune responsiveness, which may contribute to the susceptibility of multiple sclerosis or other autoimmune type diseases.

Adult↗

The effect of Lasso herbicide on human immune function as measured by in vitro assays.

Using in vitro assays, this study was undertaken to determine whether the components of Lasso herbicide formulation had an effect on the human immune system. Mononuclear cells from human peripheral blood were exposed to analytical alachlor, alachlor conjugated to human serum albumin or Lasso formulation over a concentration range from .01 microM-1.0 microM. The effects of the test materials on the following immunological functions were determined: lymphocyte proliferation induced by mitogen or antigen; antibody synthesis of IgG and IgM isotypes in pokeweed stimulated mononuclear cell cultures; cytotoxic T cell proliferation; lysis of target cells by natural killer cells and lymphokine activated killer cells. The data demonstrated that the test compounds had no significant, dose related effect on the function of immunocompetent cells. Hence, the data suggest that the components of the Lasso formulation have no effect on the human immune system.

Acetamides↗

Effect of Santoquin on humoral immune function in mice: lack of interference with selenium utilization.

Santoquin (0.25% by weight) in the diets of mice receiving adequate dietary selenium (1.0 parts/10(6] reduced the humoral immune response, as monitored by the plaque-forming cell assay, to levels exhibited by mice maintained on selenium-deficient diets (0.005 parts/10(6)). Mice exhibiting this suppression of immunity had levels of blood glutathione peroxidase, serum selenium, and liver DNA, RNA and protein similar to mice receiving selenium only. Therefore, it was concluded that Santoquin is not immunosuppressive by interfering with selenium metabolism or general tissue function, but by other unknown mechanisms.

Animals↗

Subchronic and chronic exposure to d-fenfluramine dose-dependently enhances splenic immune functions in young and old male Fischer-344 rats.

Serotonin (5-HT) has been shown to modulate various arms of the rodent immune system in an age- and sex-dependent fashion. Thus, only young (5-6 months) male and old (21-23 months) female Fischer-344 (F344) rats demonstrated an elevation in ex vivo assessed basal and IL-2 stimulated splenic NK activity as well as CON-A induced T cell proliferation after subchronic (30-44 days) administration of low doses (0.6-1.8 mg/kg per day, p.o.) of the 5-HT releaser and reuptake inhibitor, d-fenfluramine (d-FEN). In the present study when young male F344 rats were administered higher doses of d-FEN (3-9 mg/kg per day, p.o.) for 30-39 days, there was a dose-dependent decrease in basal NK activity which returned to control levels after overnight incubation with IL-2. Further, only the rats receiving 6 mg/kg per day of d-FEN exhibited an elevation (40%) in CON-A mitogenesis compared to controls. When 15-month-old male rats were treated with d-FEN (0.6 mg/kg per day, p.o.) for 8 months, their NK and T cell activities at 23 months were not statistically different from young (7 months old) control animals. Importantly, neither the old rats treated with d-FEN nor the young control animals evidenced splenic or hepatic hypertrophy and lesions. In contrast, the old control animals showed increased NK activity (250%) and decreased T cell mitogenesis (300%) which correlated with a high incidence of splenic pathology. Thus, long-term exposure to d-FEN appears to maintain the NK and T cell arms of the immune system at youthful levels and prophylactically reduce the splenic pathology associated with advancing age. These results suggest that long-term exposure to increased levels of 5-HT may be beneficial to the immune system of the aging male F344 rat.

Aging↗

Standardisation and quality assurance of lymphocyte proliferation assays for use in the assessment of immune function. European Concerted Action on Immunological and Virological Markers of HIV Disease Progression.

Lymphocyte proliferation is a widely used technique to assess immune competence. However, the technique is subject to a large degree of variation, some biological and some technical. In this study, the components of variation in whole blood proliferation assays were analysed over time, using both antibody and mitogenic stimulants. The levels of variation within individual samples, between individuals and between groups of individuals over time were examined. A method of transforming the data is proposed which reduces the coefficients of variation to an acceptable level, and which expresses individual results as a standardised count. This method overcomes the problem of different levels of absolute counts, it corrects for time sensitive errors and allows data from multiple laboratories to be pooled.

Antibodies, Monoclonal↗

Superoxide dismutase as modulator of immune function in American white shrimp (Litopenaeus vannamei).

The immunomodulatory action of superoxide dismutase (SOD) and its possible use as an indicator of immune responses in American white shrimp (Litopenaeus vannamei) were studied. Juvenile shrimp were immersed in aerated beta-glucan and sulfated polysaccharide solutions for 6 h. SOD activity in haemocytes and muscle was quantified to evaluate whether beta-glucan and sulfated polysaccharide induce immunostimulatory activity. Haemocytes and muscle showed similar increased levels of SOD activity (1.5- and 1.4-fold that of control, respectively). Total haemocyte count decreased within the first 24 h after challenge with immunostimulants, but total haemocyte count and total soluble haemocyte protein increased over normal values after 48-120 h. Single immunostimulation with beta-glucan and sulfated polysaccharide is sufficient to generate an increase in the antioxidant activity of L. vannamei SOD.

Adjuvants, Immunologic↗

Effect of 50- and 100-mg vitamin E supplements on cellular immune function in noninstitutionalized elderly persons.

BACKGROUND: It has been suggested that vitamin E can counteract the age-associated decline in cellular immune responsiveness (CIR). Particularly, T helper cell type 1 (Th1) activity, ie, interferon (IFN) gamma-producing Th1 activity and, hence, delayed-type hypersensitivity (DTH) would be enhanced by vitamin E supplementation. OBJECTIVE: Our aim was to study the effects of 6 mo supplementation with 50 and 100 mg vitamin E on CIR in the elderly. DESIGN: A double-blind, placebo-controlled trial was conducted in 161 healthy elderly subjects aged 65-80 y. CIR was measured in vivo by means of DTH skin tests and in vitro by assessing the production of interleukin (IL) 2, IFN-gamma (a typical Th1 cytokine), and IL-4 (a typical Th2 cytokine) by peripheral blood mononuclear cells after stimulation with phytohemagglutinin. RESULTS: Both DTH and IL-2 production showed a trend toward increased responsiveness with increasing dose of vitamin E. However, IFN-gamma production decreased whereas IL-4 production increased in the groups receiving vitamin E. Only the change in the number of positive DTH reactions was borderline significantly larger in the 100-mg vitamin E group than in the placebo group (P = 0.06, Bonferroni adjusted). Subjects receiving 100 mg vitamin E with low baseline DTH reactivity or who were physically less active had a significantly larger increase in the cumulative diameter of the skin induration resulting from the DTH test than did the placebo group (P = 0.03), although this difference was not significant after Bonferroni correction (P = 0.07). CONCLUSION: Possible beneficial effects of 100-mg vitamin E supplementation may be more pronounced in particular subgroups of elderly subjects.

Aged↗

The influence of partial or total thymectomy during open heart surgery in infants on the immune function later in life.

Infants undergoing open heart surgery often have all or part of their thymus removed. The activity of the immune system has not been investigated thoroughly in these children, and only shortly after the operation. Therefore, it was decided to investigate the activity of the immune system in more detail in children several years after their operation. Peripheral blood samples from 19 children who had undergone open heart surgery during their first months of life was collected (study group) and from 19 age- and gender-matched children (control group). The activity of the immune system was evaluated by measuring the number of different cell types in peripheral blood, the phenotype of lymphocytes and the response of T cells following in vitro stimulation by mitogen, tetanus toxoid and measles antigen. The study group had significantly lower counts of total lymphocytes, which was reflected in a lower number of T cells but not B cells. Furthermore, the study group had significantly lower proportion of T cells (CD3(+)) and helper T cells (CD4(+)), but not cytotoxic T cells (CD8(+)). The level of neutrophils in peripheral blood was significantly higher in the study group. This may indicate enhanced innate immunity when the acquired immunity is defective. The results indicate a shift to extrathymic T cell maturation, which is less efficient for CD4(+) helper cells than for CD8(+) cytotoxic cells.

Antigens, Viral↗

Strain- and sex-linked effects of dietary polyunsaturated fatty acids on tumor growth and immune functions in mice.

In the present paper, we studied the influence of different levels of dietary polyunsaturated fatty acids (PUFA) on the immune system and tumor growth in young mice. Female BALB/c mice fed a PUFA-rich diet display an enhanced body growth, proliferative response to mitogens in vitro, and rate of growth of a spontaneous transplantable adenocarcinoma as compared to PUFA-poor diet-fed females. Such effects are, however, limited by sex and strain background genes located outside the H-2 complex. In effect, the influence of dietary PUFA content is evident in female but not in male BALB/c mice. Moreover, in female DBA/2 mice with the same haplotype (H-2d) of the major histocompatibility complex as that of BALB/c mice, low dietary PUFA determines a reduced tumor growth only, but it does not affect body growth and proliferative response to mitogens in vitro.

Adenocarcinoma↗

Immune function and renal transplantation in Fabry's disease.

A deficient leucocyte immunological function could cause the reported high rate of lethal infections following renal transplantation in patients affected by Fabry's disease. We have studied humoral immunity, peripheral lymphocyte subsets, mitogenic lymphocyte response in vitro and granulocyte function in three patients with Fabry's disease. The immunological state appears to be quite similar to that of the uraemic population in general, not showing any specific impairment.

Fabry Disease↗