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[Effect of aging on the gut-associated lymphoid tissue--comparison of the systemic immune functions].

Immune functions generally decline with aging. However, the onset and the rate of the functional decline may be different in each lymphoid compartments. We studied the effects of aging on the murine Peyer's patch cells, which is a part of gut-associated lymphoid tissue (GALT). Peyer's patch cells of 21-months old aged mice retained a greater capacity to proliferate in the response to mitogens, and non-specific immunoglobulin synthesis in vitro. But Peyer's patch cells of 29-months old aged mice showed a distinct functional defect. So, it is suggested that Peyer's patch cells maintain immune functions until certain point of aging and rapidly lose their functions. It is reasonable that GALT maintains the immune functions until certain point of aging, because GALT is one of the first line of defence mechanism and always contact with many dietary and bacterial antigens.

Aging

Sleep deprivation in the rat: VII. Immune function.

Immune function studies were performed on splenic lymphocytes obtained from rats subjected to total or paradoxical sleep deprivation. Spleen cell counts, in vitro lymphocyte proliferation responses to mitogens, and in vitro and in vivo plaque-forming cell responses to antigens were obtained. Sleep-deprived rats were roughly equivalent to both their yoked controls and home-cage controls in all assays. The results do not support the hypothesis that sleep deprivation results in immune suppression as measured by the above-mentioned parameters.

Animals

Effects of therapy with azathioprine and prednisolone and ultraviolet irradiation on mouse skin immune function and immune cell markers.

The effects of ultraviolet irradiation (UVI) (290-400 nm) and/or systemic immunosuppressive drug therapy (azathioprine and prednisolone) on the immunocompetence of the skin of hairless (HRA/Skh-1) mice were investigated. Mice were studied for the density of ATPase+, Ia+ and Thyl X 2+ cells in the dorsal epidermis and contact hypersensitivity (CH) of skin to dinitrofluorobenzene (DNFB). Prednisolone therapy alone and UVI alone each reduced the densities of the three skin immune cell markers and CH responsiveness; azathioprine therapy alone had no such effects. When a suberythemal dose of UVI that induced a moderately depressive effect on these two skin parameters was used, additional azathioprine therapy produced no further depression; additional prednisolone therapy further depressed the densities of ATPase+ and Ia+ cells and CH responsiveness; additional therapy with combined azathioprine and prednisolone induced profound depression of the incidences of the three immune cell markers and of CH responsiveness. These data point to interaction between azathioprine/prednisolone therapy and UVI in depressing local immune function within skin which may contribute to the increased susceptibility of the sun-exposed skin of immunosuppressed kidney transplant recipients to infective and carcinogenic processes.

Adenosine Triphosphatases

Phytohemagglutinin skin test responses to evaluate in vivo cellular immune function in rats.

It is often necessary to have a small animal model which permits the sequential evaluation of functional immune status over a period of time. We report here the in vivo, intradermal response to phytohemagglutinin which produces an area of induration that is histologically similar to a typical delayed cutaneous hypersensitivity response, and that provides fast, quantitative, reproducible results similar to those observed with standard but more laborious and variable in vitro tests of immune function. For small animal studies this has the advantage of permitting longitudinal evaluations over time without sacrificing the animal. Using phytohemagglutinin-microprotein (0.2 mg/0.1 ml), injected intradermally, a delayed cutaneous hypersensitivity-like response is induced which is maximal at 24 hr. When immune function was altered either by treatment with a chemical immunosuppressant (ethanol) or by hormonal manipulations (hypophysectomy and rat growth hormone), the delayed cutaneous hypersensitivity-like response (area of induration) correlated closely with both macrophage migration inhibitory factor changes (r = 0.98; P less than 0.001) and mixed lymphocyte reaction changes (r = 0.99; P less than 0.05). These observations suggest that this technique correlates well with standard in vitro measures of immune response and may thus permit an in vivo estimation of immune reactivity.

Animals

Immune function and survival in a long-lived mouse strain subjected to undernutrition.

Functional immune changes were monitored in populations of the long-lived C57BL/6J strain of mice which were subjected to dietary restriction from time of weaning or subjected to such restriction both before and after weaning, along with the appropriate control populations. Responses to T and B cell mitogens (PHA, Con-A, pokeweed, bacterial lipopolysaccharide, and PPD), to injected sheep red blood cells, and measurement of skin allograft rejection rates were followed. Early in life, restricted mice appear immunosuppressed, as judged by all these parameters. Skin allograft rejection remained suppressed until relatively late in life. Other responses tended to reverse from the earlier pattern; by mid-life restricted mice responded better than controls. Dietary restriction profoundly affects the immune system. Mice on such regimes display anatomic and certain immune functional changes which suggest that the immune system may mature less rapidly and stay "younger" longer than in the controls. Furthermore, dietary restriction results in prolongation of life span.

Animals

[Detection of erythrocyte immune function and circulatory immune complex in myasthenia gravis].

The circulating immune complexes (CIC) and erythrocyte immune function in myasthenia gravis were studied. In order to examine CIC in the patients with myasthenia gravis the complement sensitized yeast cell agglutination (CSYCA) test and anti-C3-ELISA were used. The CIC positive rate was 92.3% in the patients tested. The CIC test was all negative in the normal control subjects. The levels of CIC were remarkable elevated in the patients with myasthenia gravis (P less than 0.01). It was found that the rosette rate of red blood cell C3b receptor was 11.27 +/- 3.27% in the CIC negative patients with myasthenia gravis and 17.60 +/- 5.10% in CIC negative patients with myasthenia gravis. The erythrocyte immune function decreased remarkably in the CIC positive patients with myasthenia gravis (P less than 0.05). The relationship between the decrease of the erythrocyte immune function and myasthenia gravis is discussed.

Agglutination Tests

Psychological and neuroendocrine measures related to functional immune changes in anticipation of HIV-1 serostatus notification.

Our previous work indicated that gay males ultimately found to be seronegative showed impaired lymphocyte proliferative responses to phytohemagglutinin (PHA) and pokeweed mitogen (PWM) upon entering a study in which they would be notified of their human immunodeficiency virus-Type 1 (HIV-1) antibody status. To examine the degree to which alterations in various neuroendocrine and psychological markers might be related to this phenomenon we measured plasma cortisol, beta-endorphin, denial coping strategies, intrusive thoughts related to AIDS risk, and several affective distress markers in 46 HIV-1 seronegative subjects at each of the timepoints previously studied. Results indicated that cortisol levels were elevated at study entry and decreased across the subsequent five-week period--mirroring the changes in mitogen responsivity across these timepoints. Analyses of individual differences showed that higher baseline cortisol and lower denial coping scores predicted lower PHA values at baseline. Persisting intrusive thoughts about risk of HIV-1 infectivity (after seronegativity notification) were consistently associated with higher plasma cortisol levels. Finally, beta-endorphin levels did not change significantly across the 10-week observation period, were not associated with psychological variables, and were inconsistently associated with immune functioning.

AIDS Serodiagnosis

Impairment of thymus-dependent immune functions by exposure of the developing immune system to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

The effects of TCDD exposure on the developing immune system were investigated in F344 rats. Fetal and neonatal rats were exposed to TCDD through maternal dosing (5 microgram/kg) on day 18 of gestation and on days 0, 7, and 14 of postnatal life (group I). Another group of neonatal rats was exposed to TCDD through maternal dosing on days 0, 7, and 14 of postnatal life only (group II). Body weights and thymus/body weight ratios were found to be suppressed up to 145 days of age in group I, but only up to 39 days of age in group II. Parameters of cell-mediated and humoral immune function were investigated. TCDD suppressed cell-mediated immune function without affecting humoral immune function. Suppression of T-cell function was selective in that "helper" cell function was not suppressed.

Animals

The effect of immunosuppressive chemotherapy on immune function in patients with malignant disease.

This paper reviews studies previously conducted on the effect of anticancer drugs on immune function in man. It provides new data reporting on the effect of short intensive courses of cytotoxic drug therapy on B-lymphocyte and T-lymphocyte number in cancer patients. Both types of lymphocyte were found in this investigation to be equally sensitive to cytotoxic drugs. The degree of absolute cell number reduction and rate of recovery were similar for T-lymphocytes and B-lymphocytes. Other workers have demonstrated, however, that with prolonged administration of cytotoxic drugs B-lymphocyte number and function are more adversely affected than are T-lymphocyte number and function. Immune function which had been suppressed by continuous programs of chemotherapy for periods of up to 2-3 years will, in certain groups of patients, recover to normal or almost normal levels of function. Short courses of combination drug chemotherapy may be followed by "rebound-overshoot" recovery of immune function. This has been associated with a more favorable clinical course than in situations where it does not occur. Chemotherapy and chemoimmunotherapy programs in clinical oncology ought ideally to be initially evaluated for the effect that they have on immune function. This will permit the development of drug dose and time schedules which allow for recovery of immune function and may possibly lead to augmented antitumor responses.

Antibody Formation

Investigations on the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on parameters of various immune functions.

The effects of TCDD exposure on parameters of immune function during the developmental period were investigated. Exposures were performed in Fischer/Wistar rats. Fetal and neonatal rats were exposed to TCDD through maternal dosing (5 micrograms/Kg) on day 18 of gestation and on days 0, 7, and 14 of postnatal life (group 1). Another group of neonatal rats were exposed to TCDD through maternal dosing on days 0, 7, and 14 of postnatal life only (group 2). Body weights and relative thymus weights were found to be suppressed up to 135 days of age in group 1 but only up to 35 days of age in group 2. Parameters of cell-mediated and humoral immune function were investigated. TCDD suppressed cell-mediated immune function without affecting humoral immune function. TCDD-exposed animals had recovered normal cell-mediated immune function by 270 days of age. A group of inbred Fischer rats was exposed to TCDD as described for group 1 above. At 45 days of age these animals were utilized in lymphocyte homing studies. It was found that TCDD exposure alters homing patterns of lymphocytes from exposed animals when adoptively transferred to untreated animals. In addition, lymphocytes from nonexposed animals did not home normally when injected into TCDD-exposed recipients.

Animals

Effect of dietary protein and amino acids on immune function.

The normal immune system has local and systemic components which are influenced by a variety of alterations. Impaired host immunity is associated with neoplasia, protein calorie malnutrition, and the administration of immunosuppressive drugs. It is well accepted that protein calorie malnutrition impairs host immunity with particular detrimental effects on the T-cell system, resulting in increased opportunistic infection and increased morbidity and mortality in hospitalized patients. Individual nutrient substrates may also have a major influence on the immune system. Individual amino acids are often described as essential, based on requirements for optimal growth and maintenance of positive N balance. Arginine has been demonstrated to be essential to the traumatized host and may have tissue-specific properties which influence components of the immune system. Thus, arginine may be of value in clinical situations where the immune system is compromised. In a series of experiments in normal animals, arginine was demonstrated to enhance cellular immune mechanisms, in particular T-cell function. It also has a marked immunopreserving effect in the face of immunosuppression induced by protein malnutrition and increases in tumor burden. In postoperative surgical patients, arginine supplementation results in enhanced T-lymphocyte response and augmented T-helper cell numbers, with a rapid return to normal of T-cell function postoperatively compared with control patients. These data suggest that arginine supplementation may enhance or preserve immune function in high-risk surgical patients and theoretically improve the host's capacity to resist infection.

Amino Acids

Dietary fat and immune function. II. Effects on immune complex nephritis in (NZB x NZW)F1 mice.

(NZB x NZW)F1 mice initiated on fat restriction at weanling were significantly protected from the development of immune complex glomerulonephritis. Whereas the mice on high-fat intake demonstrated immune depositions both in capillary walls and mesangial areas in a diffuse granular pattern, those on a low-fat diet with caloric content similar to the high-fat diets exhibited mesangial confinement of the depositions of immunoglobulins, complement, and retroviral gp70. In association with these divergent patterns of immune deposition, the mice on high-fat diets had evidence of extensive diffuse cellular proliferation, wire loop lesion, and sclerosis in the glomeruli. In contrast, most of the mice on the low-fat diet showed only mesangial cell and matrix proliferations. In addition, the group of mice fed high saturated fat showed more severe glomerular pathology as compared to those fed high unsaturated fat. Paradoxically, levels of circulating immune complexes (as measured by the polyethylene glycol precipitation technique) in the high saturated fat group were low and did not correlate with the findings by light and immunofluorescence microscopy. These findings suggest that dietary fat restriction can serve as either a prophylactic or effective therapeutic approach to murine lupus nephritis.

Animals

[Determination of partially cellular and local immune function in patients with spleen deficiency syndrome].

The immune function status as reflected by the peripheral blood OKT system T cell subset classification and the lymphocyte in vitro interleukin 2 (IL2) secretory function were determined in 30 patients with Spleen deficiency syndrome and 20 normal subjects in this study. Experimental results decreased cellular immune function and disturbance of immune regulatory mechanism in the patients. Its manifestations were decreased number of total T lymphocytes and helper T cells (Th), relatively increased suppressor T cells (Ts), abnormal rate of Th to Ts, no marked change of IL2 secretory function of T cell in vitro, increased SIgA level before stimulating with acid but marked decreased SIgA level after stimulating. All these suggest the compensatory stage of local immune function.

Adult

Inhibition of immune functions by antiviral drugs.

Immune functions were evaluated in vitro for PBMC isolated from healthy donors and cultured with the antiviral agents, 3'-azido-3'-deoxythymidine (AZT), ribavirin, ganciclovir, 2'3'-dideoxyinosine (ddI), or acyclovir. To identify methods for assessing the effects of antiviral drugs on immune cells, the PBMC response to mitogens, Con A, or phytohemagglutinin was evaluated from measurements of [3H]thymidine and [14C]-leucine incorporation, cell growth, cellular RNA, DNA, and protein levels, and the PBMC proliferative cycle (i.e., progression from G0----G1----S----G2 + M). At clinically relevant concentrations, AZT, ribavirin, or ganciclovir diminished PBMC responsiveness to mitogen. The numbers of proliferating cells in G1, S, and G2 + M phases of the cell cycle, DNA content, and [3H]thymidine uptake were decreased in cultures treated with AZT, ribavirin, or ganciclovir. AZT or ribavirin but not ganciclovir reduced RNA and protein in the cultures and inhibited cell growth. Whereas AZT, ribavirin, or ganciclovir were antiproliferative, ddI or acyclovir had little, if any, effect on PBMC mitogenesis. The inhibitory effects of antivirals on immune cells may contribute to the immune deterioration observed in patients following prolonged use of the drugs.

Acyclovir

Strain-dependent association between immune function and paw preference in mice.

The relationship between immune function and the preferred direction of behavioral asymmetry was examined in several mouse strains. Mixed leukocyte reaction, natural killer cell activity, cytotoxic T lymphocyte response and lymphoproliferation in response to mitogens were investigated in animals with left or right paw preference. From the 7 strains and substrains examined, it appeared that differences in immune function between left and right pawed mice, when present, vary in directionality. Thus, in C3H/HeJ and 129/J, left pawed mice had higher immune responses than right pawed mice, whereas in C3H/HeNCr MTV- and BALB/cJ animals, the reverse was found. In C3H/HeNCr MTV+, C57BL/6J and Collin's heterogenous control population for the high/low asymmetry lines, no differences between animals with left or right paw preference were found. The statistical significance of these differences were not uniform for all the immune parameters studied. These data indicate that the association between immune function and preference for using the left versus right paw is a strain-dependent phenomenon and may suggest that the inconsistent evidence for an association between immune deficiency and left-handedness could be due to genetic heterogeneity among subpopulations.

Animals

Enhancement of cellular immune function during cold adaptation of BALB/c inbred mice.

The cell-mediated immune function of cold-adapted BALB/c inbred mice was studied in experiments of splenic lymphocyte blastogenesis, indicated by tritium-labeled deoxythymidine incorporation and SDS-PAGE autoradiography of synthetic proteins in lymphocytes. Male BALB/c inbred mice were randomly divided into two groups: control (living at 25 degrees C) and cold-exposed (living at 2 degrees C). Results are as follows: in contrast with the control group, there was an obvious fluctuation of cell-mediated immune function in the cold-exposed group at initial cold exposure because of transient stress to cold; then cell-mediated immune function gradually recovered to control level. From Day 15, the cell-mediated immune function of the cold-exposed group was remarkably enhanced. On Day 15, the lymphocyte blastogenesis rate was increased by 20.66% (P less than 0.05), which implies the onset of cold adaptation; on Days 21 and 31, the rates increased by 80.15% (P less than 0.05) and 40.36% (P less than 0.05), respectively. Two to six months later, with continuing cold exposure, the murine lymphocyte blastogenesis rate in the cold-exposed group remained higher than that in the control group. The lymphocyte protein synthesis of the cold-exposed group, indicated by tritium-labeled leucine incorporation, apparently increased on Day 15 and the stimulated rate was 101.47% (P less than 0.05). SDS-PAGE autoradiography of synthetic proteins in lymphocytes demonstrated that after 2 weeks of cold exposure, protein bands were enriched in both quantity and quality. These results are identical to the results obtained from lymphocyte blastogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization

Lack of a relationship between immune function and chemically induced hepatocarcinogenesis in B6C3F1 mice.

The relationship between immune function and chemically induced hepatocarcinogenesis was studied employing an in vivo murine model. Neonatal B6C3F1 mice were given a single carcinogenic dose of diethylnitrosamine (DEN) and the time-response kinetics for the early (foci of alteration) and late (adenomas/carcinomas) phases of hepatocellular carcinogenesis were compared to changes in hematopoiesis and immune functions associated with immune surveillance and natural resistance. Increases in hematopoiesis occurred just prior to or concurrent with the appearance of hepatocellular carcinomas, while increased macrophage and natural killer cell cytotoxicity and suppression of cell-mediated immunity occurred following tumor appearance and progressed with increasing tumor burden. Neither immunological nor hematopoietic changes were associated with early phases of hepatocarcinogenesis, as monitored by the appearance of altered hepatocellular foci. Although changes in hematopoiesis may represent an early indicator for hepatocarcinogenesis in the mouse tumor model, the data suggest that altered immune surveillance and natural resistance are not factors in the development of chemically induced hepatocellular tumors, and the changes in immune function are probably secondary to tumor development.

Animals

[Determination of red blood cell immune functions in patients with pulmonary tuberculosis].

Red blood cell immune functions were determined in 106 patients with pulmonary tuberculosis (tbc) and in 37 blood donors as a control group. In control group, RBC-C3bRR was 17.2 +/- 6.5%, RBC-ICR was 4.0 +/- 2.2%. In the group, both RBC-C3bRR and RBC-ICR levels were elevated in 23 patients, only RBC-C3bRR level or RBC-ICR level rose in 40 or 31 cases respectively. so, 88.6% of patients showed elevation of RBC immune function. The pathological changes were also correlated with the level of RBC-ICR, RBC-C3bRR significantly (P < 0.01). The authors suggested that the measurement of RBC immune functions might be useful in diagnosis, assessment of the severity and outcome of pulmonary tuberculosis.

Adolescent