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[Cellular immunity function in HIV-1-infected persons].

The data on the state of cell-mediated immunity in patients with AIDS-related complex are presented. The synthetic peptide of membrane protein gp120 of HIV-1 was shown to inhibit leukocyte adhesion in persons under examination, as well as to have the tendency towards inhibiting the chemotaxis of migratory cells. The maximum effect was achieved at a peptide concentration of 10(-6) M. The data obtained in this investigation suggest the presence of specific cell-mediated sensitization to the fragment of protein gp120, detected by the adhesion inhibition test with the use of spectrophotometric techniques and the capillary evaluation of the chemotaxis of migrating cells, in patients with AIDS-related complex.

AIDS-Related Complex↗

[Changes in the lymphoid cells of DNA and purine nucleotide synthesis and sensitivity to glucocorticoids associated with impairment of differentiation and immune function during tumor growth in mice. Thymocytes].

Some biochemical mechanisms underlying the impairments of cellular immunity were studied in C3Ha mice in the course of growth of transplantable and induced (ortoaminoazotoluol) solid hepatomas. During intensive hepatoma growth, the adenosine deaminase activity in host thymocytes was shown to be drastically (6 times) reduced, resulting in the elevation of dATP and dGTP concentrations (6- and 7-fold, respectively), the potential inhibitors of ribonucleoside diphosphate reductase. Consequently, the rate of DNA synthesis was reduced as can be evidenced by the decrease of (a) thymidine kinase activity, (b) 14C-thymidine incorporation into DNA, and (c) dTTP and dCTP pools. By the terminal period of hepatoma growth (both transplantable and induced one), the serum corticosterone content increased 3- and 8-fold, respectively. At the same time, specific binding of [3H]triamsinolone acetonide by thymocytes was augmented and the activity of terminal deoxynucleotidyl transferase increased the latter alterations, which can be regarded as a reflection (including other parameters mentioned) of the arrest of T-lymphocyte differentiation at the level of immature cortex thymocytes.

Adenosine Deaminase↗

Development of cellular immune functions in neonatal to weanling mice: relationship to Cryptosporidium parvum infection.

Lymphocyte phenotypes and cellular immune responses (blastogenesis and production of cytokines) to Cryptosporidium parvum were determined for spleen cells taken from BALB/c mice. These parameters were measured in mice at 1, 2, 3, and 4 wk of age, either exposed or not exposed to C. parvum in vivo. The percentage of T cells and the T-helper subset increased from weeks 2 to 4; B cells reached a peak percentage at 2 wk. Blastogenic responses were elevated at 1 wk and declined to a low level during weeks 2 to 4. Interferon-gamma production was maximal at 4 wk. No interleukin-5 production was seen. Data obtained were similar for cells from mice either exposed or not exposed to C. parvum in vivo. These data indicate that age-related changes, particularly the increased percentage of T cells and increased interferon-gamma production, are temporally related to the acquisition of resistance to colonization of mice with C. parvum. The data also indicate that these age-related changes occur in the absence of specific exposure to parasite antigens.

Aging↗

Acquisition of immune function during the development of the Langerhans cell network in neonatal mice.

The immunological function of the Langerhans cell (LC) network in neonatal skin was examined by defining the development of cutaneous immunity relative to the structure, phenotype and function of the epidermal LC network in neonatal, juvenile and adult mice. Analysis of epidermal sheets showed the presence of major histocompatibility complex (MHC) II+, multilectin receptor DEC-205- cells within the epidermis of 3-day-old mice; both cell density and DEC-205 expression increased until day 14. When visualized with antibodies directed at MHC II, the network was poorly formed in 3- and 7-day-old mice, as there was a lower cell density and poor MHC II expression on dendritic processes, compared to mice at day14. Application of a fluorescent antigen to 3-day-old mice revealed that the LC were inefficient in transporting antigen to the draining lymph node. There was an improvement at day 7 and by day 14 comparable numbers of antigen carrying cells were detected in the lymph nodes of 6-week-old mice. The reduced antigen carriage in 3- and 7-day-old mice correlated with a poor contact sensitivity response. This was not simply due to failure to present antigen, but development of immunosuppression, as transfer of T cells from adult mice that were previously treated with antigen when they were 3 days old, to adult recipients resulted in antigen specific immunosuppression. Analysis of CD80 and CD86 expression showed that LC from day 3 skin expressed CD80, but not CD86 and application of antigen through this skin was inefficient in upregulating CD86. These findings indicate that when the neonatal LC network is poorly developed it is functionally immature and antigen applied through this 'functionally immature network' results in antigen specific immunosuppression.

Aging↗

[The characteristic changes of immune function with aging--analysis of the mechanisms].

The most prominent immunological abnormalities in the aged were reduced immune response against foreign antigens and increased auto-antibody production against intrinsic antigen. To explain these immunological abnormalities, we examined the various functions of human lymphocytes from aged and young groups at cellular, molecular and genetic levels. The results indicate: The first, T cells from the aged showed significantly reduced proliferative response not only to specific antigen TAP but also to mitogen PHA or combined stimulation of PMA and ionomycin. The second, the number of IL-2 receptor, particularly high affinity ones, on aged T cells were significantly reduced in the aged after TAP and PHA stimulation. The third, the ability to express Tac (p55) and p70/75 of IL-2R and to internalize the rIL-2 bound to the receptor were reduced in aged T cells. The fourth, although the ability to proliferate in response to SAC stimulation was two folds less in the aged B cells than that in the young ones, the capacity to differentiate into IgG and IgA class ISC after the combined stimulation with SAC and partially purified BCDF were rather increased on the basis of the number of viable cells recovered. The fifth, the amount of IL-2 activity produced by aged T cells was ten fold less than that by young ones, but the amount of BCDF activity produced by aged T cells was three folds higher than that by young ones after PHA stimulation. An inverse correlation between IL-2 activity and BCDF activity was found when the both activities were determined in the same sample.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of exchange transfusion on cell-mediated immune function following thermal injury.

We assessed the effect of syngeneic and allogeneic exchange transfusion (XTF) on cell-mediated immunity in a murine burn model. Mice were given a 30% TBSA scald injury and lymphocyte function was monitored with the popliteal lymph node assay for host-versus-graft (HVG) or graft-versus-host (GVH) response. Nonexchanged burned animals exhibited suppression of GVH response on postburn days (PBD) 3 and 8 and suppression of HVG response on PBD 3, 8, 11, and 14. Syngeneic XTF stimulated GVH response on PBD 3, and significantly improved both GVH and HVG response to alloantigens on postburn days 3 and 8 compared to the response of burned controls. Allogeneic XTF significantly improved GVH response on PBD 3 and 8, but did not improve HVG response. Restoration of lymphocyte function in all experimental groups occurred between PBD 14 and 18 and coincided with wound healing.

Animals↗

[Immune function and organ failure. Immunomodulation with nutritional support--an update].

Today, substrates with immunomodulatory effects are not only identified in all groups of macronutrients, but also in the domains of vitamins and traceelements. Mainly they interfere with 3 areas of the immune response: 1. the mucosal barrier function, 2. the cellular defense function, and 3. the local or systemic inflammatory response. Enteral formulas enriched with immune-enhancing diets are already in clinical use to encounter "immunoparalysis" of cellular defense during critical illness. Considering defined outcome variables, indeed, current clinical studies point out some improvements. Using an evidence based approach, a grade A recommendation was proclaimed for its broad clinical use. For defined subgroups of patients, however, presenting with most severe appearances of SIRS and consecutive organ failure, the current concept of enteral immunonutrition remains to be a matter of debate, and the evidence of clinical benefits persist to be questionable.

Adjuvants, Immunologic↗

Effect of micronutrient status on natural killer cell immune function in healthy free-living subjects aged >/=90 y.

BACKGROUND: Natural killer (NK) cells play a role in natural immunity against tumor and infected cells. Advanced aging is associated with functional impairment of NK cells and increased susceptibility to nutritional deficiencies. OBJECTIVE: Our objective was to test whether micronutrient status affects NK cell activity in an older population. DESIGN: The relations between NK cell variables (percentage of leukocytes and cytotoxicity) and blood concentrations of selected micronutrients were studied in 62 healthy, free-living northern Italian subjects (25 men, 37 women) aged 90-106 y. Anthropometric measurements were also made. RESULTS: All subjects were well nourished according to age-specific anthropometric norms but many of them had micronutrient deficiencies. The prevalence of micronutrient deficiency was highest for selenium (in approximately 50% of both sexes), zinc (in 52% of men and 41% of women), and vitamin B-6 (in 40% of men and 59% of women), followed by vitamin A (in 16% of men and 27% of women) and vitamin E, vitamin B-12, and folate (each in <10% of both sexes). Ubiquinone-10 status was inadequate in 40% of women and 24% of men (P = 0.02). The percentage of NK cells was associated with serum zinc (men: r = 0.573, P = 0. 007; women: r = 0.373, P = 0.031) and selenium (women: r = 0.409, P = 0.018) concentrations. In women only, NK cell cytotoxicity at different effector-target cell ratios was positively associated with plasma vitamin E and ubiquinone-10 concentrations (P < 0.05). No significant associations with NK cell variables were found for the other measured nutrients. CONCLUSIONS: The results of this study strengthen the hypothesis that individual micronutrients may affect the number and function of NK cells in old age. The study also confirms the high prevalence of micronutrient deficiencies in healthy and apparently well-nourished persons aged >/=90 y.

Adult↗

The effect of UV therapy on immune function in patients with psoriasis.

Ultraviolet radiation (UVR) is known to suppress some cell-mediated immune responses to antigens encountered during or soon after exposure. Phototherapy is widely used in psoriasis, and this study was undertaken to monitor changes in a range of immunological parameters during standard courses of treatment, with the aim of ascertaining whether such modulations contribute to the effectiveness of therapy. The responses of 17 patients with psoriasis undergoing UVB therapy, and four receiving PUVA therapy, were compared with 15 patients receiving coal tar treatment and four normal subjects undergoing UVB irradiation. In each case, samples were taken before starting therapy, after 4 weeks of therapy, and 4 weeks after completion of treatment. Serum immunoglobulin isotypes and complement components were within normal ranges in most of the psoriasis patients, and remained unchanged throughout therapy. Similarly, percentages of subsets of peripheral blood mononuclear cells (PBMC) were normal, and were unaltered by treatment. Patients who were already infected with herpes simplex virus (HSV), as demonstrated by a positive lymphoproliferation test in vitro, were monitored for asymptomatic HSV shedding and HSV recrudescences during therapy. There was little evidence that phototherapy caused reactivation of the virus. No significant alteration in lymphoproliferative response to HSV and to the mitogen concanavalin A was observed during therapy. Epidermal cells and blood adherent cells were used to present HSV to PBMC, depleted of adherent cells and enriched for T cells, in a lymphoproliferative assay. The functional antigen-presenting ability of adherent cells remained unchanged throughout therapy, whereas that of epidermal cells was suppressed during UVB irradiation and recovered, in most instances, after UVB therapy had been completed. The epidermis of patients with psoriasis contained about three times the quantity of urocanic acid (UCA) of normal subjects, whereas the UCA concentration in suction blister fluid did not differ between the two groups. During UVB irradiation, the percentage of cis-UCA rose in both the epidermis and suction blister fluid of all subjects, and it remained elevated in the blister fluid after therapy had finished. Tumour necrosis factor-alpha was measured in suction blister fluid, and its concentration did not alter consistently as a result of therapy. Whether any of the immunological parameters measured, and the changes noted, contribute to the effectiveness of phototherapy in the treatment of psoriasis remains uncertain.

Adult↗

Immune function in patients with previous yersinia arthritis: lymphocyte responses to PHA and Staphylococcus aureus strain Cowan I.

Evidence has accumulated that, first, polymorphonuclear leukocytes (PMN) and humoral factors such as fragments of complement components may regulate immune response, and second, PMN function is enhanced in HLA-B27-positive subjects. We therefore used a whole-blood culture technique to study lymphocyte proliferation in response to phytohaemagglutinin-P (PHA) in blood samples obtained from patients with previous yersinia arthritis and from healthy subjects with or without HLA-B27. In another series of experiments, mononuclear cells were separated from peripheral blood and lymphocyte responses to Staphylococcus aureus strain Cowan I, a B-cell mitogen in fetal calf serum, and to PHA in pooled normal human serum were determined. The patients and the control subjects were always tested simultaneously. The results showed no significant differences between the subject groups. This suggests that humoral factors and enhanced neutrophil function do not exert remarkable effects on in vitro lymphocyte responses to mitogens in HLA-B27-positive subjects.

Arthritis, Infectious↗

Melatonin rejuvenates degenerated thymus and redresses peripheral immune functions in aged mice.

The effect of melatonin on age-related thymic involution and peripheral immune dysfunctions was investigated. Exogenous melatonin was administered through the drinking water (15 microg/ml) of 22-month-old female C57BL mice for 60 consecutive days. Our results show that melatonin distinctly reversed the age-related thymic involution as revealed by the notable increase of thymus weight, total number of thymocytes and percentage of thymocytes at G2+S phases. More strikingly, spleen weight, total number of splenocytes and some peripheral immune capacity such as mitogen responsiveness and NK cell activity were also significantly recovered by 60 days of melatonin application in aged mice. Our findings demonstrate that even when the melatonin supplementation begins late in life, the age-related thymic involution and peripheral immune dysfunctions can be restored at least partially in old mice.

Aging↗