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Depressed immune function in epidermodysplasia verruciformis.

Epidermodysplasia verruciformis (EV) is a rare disease characterized by the early onset and unremitting progression of wart-like lesions and frequent association of cutaneous carcinomas. We report two siblings with EV. Immunologic study of both patients demonstrated normal immunoglobulin levels, normal numbers of T-lymphocytes and B-lymphocytes, but markedly depressed in vitro blastogenic reactivity to mitogens and antigens. Cutaneous anergy to a variety of common skin test antigens was noted. These observations may reflect an inherited abnormality in immune function, or the depressed immune function may result from the viral infection of EV.

Adult

Recovery of immune functions in dogs after total body irradiation and transplantation of autologous blood or bone marrow cells.

The restoration of immune functions was followed in dogs for 101 days after fractionated total body irradiation and autologous transfusion of peripheral blood leukocytes (PBL) or bone marrow (BM) cells. Median numbers of 0.9 X 10(5) granulocyte-macrophage progenitor cells per kilogram of body weight were transferred in either group of recipients. The following parameters recovered more rapidly in PBL recipients as opposed to BM recipients: total blood lymphocyte, T- and B-cell counts, serum levels of immunoglobulins IgM and IgA, in vitro blastogenic responses after stimulation with concanavalin A and pokeweed mitogen, and in vitro plasma cell formation after polyclonal B-cell activation with pokeweed mitogen with or without lipopolysaccharide. No major differences were noted for the restoration of serum IgG levels. Circulating lymphocyte and T-cell numbers remained subnormal for more than three months in both groups, whereas B-cell numbers and serum levels of IgA continued to be depressed in BM recipients only. Thus, autologous PBL restored immune functions more rapidly than did BM. Transplantation of PBL, alone or in addition to autologous BM, might also shorten the period of immunodeficiency after cytoreduction in a variety of malignancies in man.

Animals

[Influence on immune function parameters in histiocytosis-X of thymostimulin].

Immune function (mitogen and antigen stimulation, suppressor cell activity, T-cell subpopulation distribution) and immunogenetics (HLA-gene determination) were studied in 13 patients with histiocytosis-X and in 88 healthy controls. We found three clusters with significantly different immune responses (F-values greater than 4-20, p less than 0.05-0.001) against mitogenic and antigenic stimulation among the controls which differed, too, in HLA-gene distribution. As suppressor cell activity and T-cell subpopulation distribution are the same in all three control clusters, these reactivity differences should be functional ones and may be genetically determined. Patients with histiocytosis-X show a significantly reduced suppressor cell activity and their helper cells are significantly reduced compared to the controls (p less than 0.01). Furthermore, their lymphocyte reactivity does not correspond with their immunogenetics, but is significantly reduced (p less than 0.05-0.001). Suppressor cell activity, helper cells and lymphocyte reactivity normalized in all eight patients treated systemically with thymostimulin (Tp-1 Serono). It seems to be possible therefore, to influence immunological aberrations in vivo by thymostimulin. In our opinion, the results of this study justify further investigations of the immunoregulatory mechanisms of histiocytosis-X and larger prospective clinical trials with thymic factors to find out, whether such a therapy may be a real alternative to the conventional therapeutic approach in this disease.

Adult

Opioid peptides, receptors, and immune function.

The studies have clearly demonstrated that binding sites for opioid peptides, beta-endorphin, and methionine-enkephalin exist on T lymphocytes. beta-Endorphin appears to be immunodepressant, whereas methionine-enkephalin is immunostimulant. Both in vitro and in vivo studies have shown that methionine-enkephalin can influence some immune functions. Since in vitro modification of immune function requires very low concentrations, it is reasonable to believe that methionine-enkephalin plays a physiological role in the immune system. Although not well established, methionine-enkephalin appears to activate T lymphocytes via opioid receptors and triggers a series of intracellular signals leading to the activation of receptors for interleukin-2 (IL-2), OKT10, and active sheep T red blood cell receptors. Methionine-enkephalin enhances the activity of NK cells and induces the production of IL-2, which in turn may recruit and activate other T-cell subsets like CD3 and CD4. Methionine-enkephalin also enhances mitogen-induced proliferation of lymphocytes. Since preliminary studies with methionine-enkephalin in ARC patients have provided beneficial effects by the improvements in their symptoms, it will be worthwhile to extend these observations to a larger number of patients with ARC and AIDS. Finally, it appears that some endogenous opioid peptides and their analogs, in addition to methionine-enkephalin, may provide therapeutic benefits not only in ARC and AIDS but also in other immunodeficient states.

Acquired Immunodeficiency Syndrome

Stress and immune function in diabetes mellitus.

Type I diabetic men were found to have a greater number of stresses, more perceived stress per episode, greater anxiety, poorer immune function, and less metabolic control than Type II diabetic men. Degree of family support and compliance with the medical regimen did not differ. Correlation of perceived stress with immune function and metabolic control showed that Type I had more correlates than Type II, with more perceived stress associated with more depressed immune responses.

Adult

Effect of arginine on immune function in rats with obstructive jaundice.

In this study we used an experimental model produced by bile duct ligation (BDL) in rats to demonstrate relation between immune function and susceptibility to infection associated with obstructive jaundice and immunoregulatory effect of arginine in BDL rats. Our experimental results showed that thymus weight, content of lymphocytes in thymus and responsiveness to Con A in vitro were dramatically reduced in BDL rats as compared to rats with sham operation and that the impairment of lymphocyte function was significantly related to the susceptibility to infection. Arginine, as a T cell stimulator, markedly improved immune function and decreased susceptibility to infection of BDL rats.

Animals

Effect of chronic developmental lead exposure on cell-mediated immune functions.

Studies were performed to investigate the effects of chronic, low level pre- and post-natal lead exposure on cell-mediated immune function in rats. Weanling female rats were exposed to lead (as lead acetate) in their drinking water at 0, 25, and 50 ppm for 7 weeks. At the end of 7 weeks they were mated with untreated males and continued on the same dosage throughout gestation and lactation. The offspring of these females were weaned at 21 days of age and continued on the same lead exposure regimen as their mothers. These offspring were used in immune surveillance procedures between 35 and 45 days of age. Lead exposure at the levels employed had no statistically significant effect on growth and did not result in overt signs of toxicity. Thymic weights were significantly decreased in both males and females of the two lead dosage groups. Furthermore, lead exposure resulted in suppression of responsiveness of lymphocytes to mitogen stimulation and in reduced delayed hypersensitivity responsiveness. Results indicate that chronic low-level lead exposure causes suppression of cell-mediated immune function.

Animals

Different immune functions of peripheral blood, regional lymph node, and tumor infiltrating lymphocytes in lung cancer patients.

Immune functions of peripheral blood (PBL), regional lymph node (RLNL), and tumor infiltrating lymphocytes (TIL) were evaluated in lung cancer patients. PBL had many natural killer (NK) cells and the highest NK activity, and it showed the highest augmentation of NK activity by interferon-gamma (IFN-gamma) + recombinant interleukin-2 (rIL-2) among the three groups of lymphocytes. PBL had high lymphokine-activated killer (LAK) activity of against a broad spectrum of cell lines and moderate activity against autologous tumor cells by increased effector to target (ET) ratio but the lowest ability of IL-2 production of the three groups of lymphocytes. The RLNL not associated with tumor metastasis had a few NK cells and lower NK activity than PBL, but its LAK activity was almost the same but not greater than that of PBL. RLNL had the highest ability of IL-2 production among the three groups of lymphocytes. All activities of RLNL associated with tumor metastasis were lower than those not associated with tumor metastasis. TIL exclusively consisted of T-cells, especially cytotoxic/suppressor T-lymphocytes. NK activity and lymphocyte blastogenesis of TIL were lower than those of other groups. The LAK activity of TIL differed greatly with the case, and it was the highest against autologous tumor cells among the three groups of lymphocytes in three of eight cases. These findings showed that PBL, RLNL, and TIL had characteristic subpopulations of lymphocytes and different functions of host immune responses in lung cancer. Efficient augmentation of the characteristic immune responses will lead to a more effective total cancer therapy.

Adult

Effect of dichloromethylene diphosphonate (Cl2MDP) on immune function in breast cancer patients with bone metastases.

Immune function was studied in normocalcemic breast cancer patients with bone metastases treated with either dichloromethylene diphosphonate (Cl2MDP) or placebo. The results showed no significant difference between the two patient groups. This suggests that Cl2MDP does not markedly impair the host's defense mechanisms, and in this respect can be safely used in the treatment of patients with resorptive bone disease.

Adult

Immune functions in inflammatory bowel and coeliac diseases.

Different immune functions of 10 patients with glutein-sensitive enteropathy (GSE), 9 with Crohn's disease (CD), 11 with ulcerative colitis (UC) and 13 healthy controls were characterized. The numbers of suppressor T cells in GSE were comparable to those of the controls; otherwise, the lymphocyte subpopulations were decreased in these bowel diseases. In the whole-blood cultures, the lymphocyte proliferative responses to PHA were normal in the bowel diseases, but the responses to Con A were decreased in CD. In cultures with D-penicillamine, the inhibition of the helper effect of CD patients was more pronounced in PHA-stimulated cultures than in Con A-stimulated cultures. The total Ig and IgA production did not markedly differ among the groups. PWM-induced IgM secretion was significantly decreased in GSE, CD and UC, and IgG secretion in CD and UC, as compared to controls. In GSE, an increased Con A inducible suppressor cell activity was observed in the IgM production. Altogether, no clear-cut immunological imbalance was detected in any of the bowel diseases; this in agreement with previous works. However, there are some differences in the regulatory cell balance among the patients with GSE, CD and UC. The determination of lymphocyte proliferative responses to PHA and Con A together with D-penicillamine seems to provide a new immunological criterium for distinguishing between Chrohn's disease and ulcerative colitis.

Adult

Intravenous hyperalimentation with high arginine levels improves wound healing and immune function.

The purpose of this study was to evaluate the effect of increased arginine levels in intravenous hyperalimentation (IVH) therapy on wound healing and thymic immune function. Groups of SD rats, 275-325 g, underwent placement of internal jugular catheter, 7-cm dorsal skin wounding, insertion of polyvinyl alcohol sponges subcutaneously, and closure of wounds with stainless-steel sutures. Twenty-four hours later, rats were started on IVH at a rate of 0.8-1 ml/100 g body wt/hr. All IVH solutions contained 20% dextrose, adequate amounts of minerals and vitamins, and two different amino acid mixtures: (A) Fre III (4.05 g ARG/liter) (n = 13); (B) experimental (7.50 g ARG/liter) (n = 11). Solutions were isonitrogenous, and contained similar amounts of essential amino acids. After 7 days of IVH, weight gain did not differ between the two groups; however, cumulative N balance was superior in group A. Wound healing was improved in group B as assessed by fresh wound strip breaking strength, fixed breaking strength, and the amount of reparative collagen deposition as assessed by the hydroxyproline content of the implanted sponges. Group B animals also had improved thymic function as assessed by thymic weight, the total number of thymic lymphocytes/gland and mitogenic reactivity of thymic lymphocytes to PHA and Con A. The experiments indicate that high arginine levels in IVH solutions improve wound healing and thymic immune function following injury.

Amino Acids

Multiple sclerosis: in relapsing patients, immune functions vary with disease activity as assessed by MRI.

We have serially studied immunoglobulin G secretion in vitro, natural killer cell function, and concanavalin A-induced suppression in a group of seven patients with relapsing-remitting multiple sclerosis. In two patients, the development of a large clinically asymptomatic MRI lesion was accompanied by reductions in natural killer cell function, immunoglobulin G secretion in vitro (after pokeweed mitogen stimulation), and concanavalin A-induced suppression without parallel change in lymphocyte markers. We did not see this type of change in matched controls nor in stable multiple sclerosis studied serially. When clinical attacks appeared, there was no significant change in immune function. We conclude that changes in immune function correlate well with the activity of the disease as recognized by MRI. We suspect that decreased natural killer cell function, immunoglobulin G secretion in vitro, and concanavalin A-induced suppression are secondary to the large lesions recognized by MRI.

Adult

Alterations in cell-mediated immune functions induced in mouse splenic lymphocytes by polycyclic aromatic hydrocarbons.

The effects of varying doses of three polycyclic aromatic hydrocarbons, 3-methylcholanthrene (MCA), benzo(a)pyrene (BaP), and benzo(e)pyrene (BeP), on cell-mediated immune functions of in vivo mitogen-activated splenic lymphocytes were measured. Inbred mice (C57, C3H, and DBA) were given injections i.p. with phytohemagglutinin to activate splenic lymphocytes and were subsequently treated, via the same route, with polycyclic aromatic hydrocarbon compounds. Isolated and T-cell-enriched mononuclear cell populations were assayed for aryl hydrocarbon hydroxylase activity, blastogenesis, antigen-specific cell-mediated cytotoxicity, and the percentage of macrophages. Under optimal conditions of phytohemagglutinin injection (1000 micrograms/20-g mouse) for 96 hr and MCA treatment (50 mg/kg of body weight) for 24 hr prior to sacrifice, aryl hydrocarbon hydroxylase was induced 5-fold. Tumorigenic doses of MCA (10 to 50 mg/kg of body weight) suppressed blastogenesis 40 to 60% in C57 and C3H lymphocytes but had no effect on DBA splenic lymphocytes. BaP and BeP had little or no effect on blastogenesis. MCA and BaP were clearly separated from BeP in the suppression of cell-mediated cytotoxicity. MCA and BaP suppressed cell-mediated cytotoxicity 40 to 80% in T-cells from all three strains, while BeP had no effect. MCA reduced the percentage of macrophages in a dose-dependent fashion compared to a stimulatory action by BaP and BeP. These results suggest that mitogen-activated and aryl hydrocarbon hydroxylase-induced splenic lymphocytes metabolize MCA and BaP to immunocytotoxic metabolites. A suppression of monocyte-macrophage function would account for the inhibition of blastogenesis. These early alterations in cell-mediated immune functions produced by tumorigenic doses of MCA and BaP may result in defective immunosurveillance mechanisms and enhance the development of polycyclic aromatic hydrocarbon-induced tumors in responsive mice.

Animals

[Influence of dietary selenium level on immune function of rats with esophageal tumors induced by methylbenzylnitrosamine (NMBzA)].

The influence of dietary selenium of the incidence of esophageal tumor induced by NMBzA and the immune function during carcinogenesis were studied in rats fed with Torula yeast diet and survived for 18 weeks. The incidences of esophageal tumors were statistically not significant among rats on normal, high and low selenium intake (P greater than 0.05). The level of plaque forming cells (PFC), delayed type hypersensitivity (DTH), natural killer cell activity (NK) were significantly higher in the high selenium diet group than those of the low selenium diet group (P less than 0.05). The authors believe that the modulation of dietary selenium can alter the immune function of animals during carcinogenesis but the anticarcinogenic effect of selenium still needs further study.

Animals

Immune function in marathon runners.

Quantitative immunoglobulins (IgG, IgA, IgM) and leukocyte phagocytosis and killing were studied in 20 male marathon runners to determine if rigorous physical conditioning affects immune function. C3, C4, Properdin Factor B, T and B cells, and phytohemagglutinin and pokeweed mitogen stimulation of lymphocytes were determined in selected runners. Complete blood counts, including platelets, were obtained for the group. Mean immunoglobulin values for IgG, IgA and IgM were within normal limits. Ten runners (50%) had slightly low total lymphocyte counts (less than 1500/mm3). Leukocyte phagocytosis and killing was consistently normal. Nine marathoners felt that running had increased, and one felt that it had decreased their resistance to respiratory infections. This could not, however, be correlated with significant changes in immune parameters. We conclude that long distance running has no effect on immune function.

Adult

Effect of midbrain stimulus-induced analgesia on immune function in humans.

Electrical stimulation of midbrain structures produces significant and clinically useful analgesia in humans. However, it has been suggested to have immunosuppressive effects in animals. We evaluated immune function in two women who were utilizing implanted midbrain electrodes for pain control. An elevated B cell percentage was observed in one patient after a 72-h control rest period and this was followed by a reproducible fall in B cells after acute stimulation. However, midbrain electrical stimulation did not appear to have any other acute or chronic effects on these persons' immune functions.

Analgesia

[Quality of tuberous root of Liriope spicata (Thunb.) Lour. var. prolifera Y.T.Ma and Ophiopogon japonicus (L.F.) Ker-Gawl.--comparison of immune function].

This paper deals with comparative study on the immune function of the tuberous root of Liriope spicata var. prolifera and Ophiopogon japonicus. The results showed that the aqueous extract of both species mentioned above could increase obviously the spleen weight (immunity organ) of mice, enhance the clearance rate of iv charcoal particles in mice and antagonize remarkably the leukopenia caused by cyclophosphamide.

Animals