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Intestinal anaphylaxis in chickens: epithelial ion secretion as a determinant and potential component of functional immunity.

Immunity to secondary protozoan infections in chickens is accompanied by rapid onset of intestinal permeability to serum proteins, an event in mammals associated with local anaphylaxis. The permeability changes in the chicken intestine are hypothesized to be mediated by mast cell-derived paracrine factors. In a test of this hypothesis, we demonstrated, using an electrophysiological correlate of intestinal anaphylaxis (antigen-induced Cl(-) secretion), that the response of the chicken intestine to antigenic stimulation is consistent with type I hypersensitivity reactions. Day-old, single-comb-white-Leghorn chickens were sensitized to bovine serum albumin (BSA). At 3 weeks of age ileal segments were mounted in Ussing-type chambers. Serosal challenge with BSA elevated the transmural short circuit current (DeltaIsc) within 1min and was maximally expressed (DeltaIsc=50-60microA/cm(2)) within 2-3 min. The magnitude of the DeltaIsc was directly related to the concentration of antigen (10-200 microg antigen/ml), was only expressed in immunized chickens, and was blocked by the mucosal application of a Cl(-) channel blocker. Data obtained in the present investigation identify epithelial ion secretion as a potential mechanism of functional immunity in the mucosal immune system of the chicken small intestine.

Anaphylaxis↗

Glucocorticoids and immune function: unknown dimensions and new frontiers.

Despite the importance of glucocorticoids (GCs) to modern medicine, the physiological role of endogenous corticosteroids in immunomodulation is poorly understood. This article discusses evidence suggesting that endogenous GCs not only suppress but also direct and enhance immune functions. These often overlooked actions might well be more important than the inhibitory functions during host defence and the maintenance of homeostasis.

Acute-Phase Reaction↗

Effects of Ascophyllum nodosum extract on growth performance and immune function of young pigs challenged with Salmonella typhimurium.

Ninety-five pigs (initially 7.1 kg and 24 d of age) were used in a 28-d experiment to determine the effects of Ascophyllum nodosum seaweed extract (ANOD) on young pig growth performance and immune function in response to enteric disease challenge with Salmonella typhimurium (ST). Experimental treatments were arranged in a 2 x 4 factorial with main effects of disease challenge (control vs ST-challenge) and dietary addition of ANOD (0, 0.5, 1.0, and 2.0% of diet). Pigs were fed ANOD diets for 14 d and then challenged orally with ST or sterile media. There were no main effects of ANOD on growth performance end points, although there were significant quadratic effects of ANOD on ADG (P < 0.04) and final weight (P < 0.003), both being greatest at 1.0% ANOD. There was a positive linear effect of ANOD inclusion on ADFI (P < 0.07) and a negative linear effect on the gain-to-feed ratio (G/F) (P < 0.05). ST-challenge reduced ADG (P < 0.05), ADFI (P < 0.05), and G/F (P < 0.05) in the first week following challenge. Daily estimates revealed reductions in feed intake in ST-infected pigs on d 2 to 4 following infection (P < 0.05). Rectal temperature was increased maximally 2 d following ST-infection (P < 0.05). A disease challenge x time interaction (P < 0.001) was observed for serum haptoglobin and alpha1-acid glycoprotein. Serum immunoglobulin M (IgM) was not influenced by disease challenge, but IgM declined (P < 0.001) in all pigs over time. Serum immunoglobulin G (IgG) also was not influenced by disease challenge, but IgG tended (P < 0.08) to increase over time. In vitro culture of porcine alveolar macrophages with 10 mg/mL ANOD elevated (P < 0.05) prostaglandin E2 (PGE2) production over that of controls at 3 and 24 h of culture. There was no interleukin-10 response by porcine splenocytes cultured in vitro with 0.005, 0.05, 0.5, or 5 mg/mL ANOD. We conclude that this model of enteric disease elicits an acute phase response that is accompanied by increased rectal temperature and diminished feed intake. Furthermore, our results indicate some beneficial effects of dietary ANOD on growth performance and no influence of dietary ANOD on immune response in the presence or absence of ST-challenge. However, high ANOD concentrations are capable of activating porcine alveolar macrophages in vitro to secrete PGE2.

Acute-Phase Proteins↗

Normal T-cell development and immune functions in TRIM-deficient mice.

The transmembrane adaptor molecule TRIM is strongly expressed within thymus and in peripheral CD4(+) T cells. Previous studies suggested that TRIM is an integral component of the T-cell receptor (TCR)/CD3 complex and might be involved in regulating TCR cycling. To elucidate the in vivo function of TRIM, we generated TRIM-deficient mice by homologous recombination. TRIM(-/-) mice develop normally and are healthy and fertile. However, the animals show a mild reduction in body weight that appears to be due to a decrease in the size and/or cellularity of many organs. The morphology and anatomy of nonlymphoid as well as primary and secondary lymphoid organs is normal. The frequency of thymocyte and peripheral T-cell subsets does not differ from control littermates. In addition, a detailed analysis of lymphocyte development revealed that TRIM is not required for either positive or negative selection. Although TRIM(-/-) CD4(+) T cells showed an augmented phosphorylation of the serine/threonine kinase Akt, the in vitro characterization of peripheral T cells indicated that proliferation, survival, activation-induced cell death, migration, adhesion, TCR internalization and recycling, TCR-mediated calcium fluxes, tyrosine phosphorylation, and mitogen-activated protein family kinase activation are not affected in the absence of TRIM. Similarly, the in vivo immune response to T-dependent and T-independent antigens as well as the clinical course of experimental autoimmune encephalomyelitis, a complex Th1-mediated autoimmune model, is comparable to that of wild-type animals. Collectively, these results demonstrate that TRIM is dispensable for T-cell development and peripheral immune functions. The lack of an evident phenotype could indicate that TRIM shares redundant functions with other transmembrane adaptors involved in regulating the immune response.

Animals↗

The lichen rock tripe (Lasallia pustulata) as survival food: effects on growth, metabolism and immune function in Balb/c mice.

The present study was performed to investigate whether the lichen rock tripe (Lasallia pustulata) can be used as food during survival situations. The effects of 30% lichen supplementation given to female Balb/c mice were studied on growth rate, metabolism and immune functions. After 3 weeks on this diet, it was found that the lichen supplementation did not affect the growth rate or the well-being of the animals. The growth rate tended to be higher in the lichen group when compared to control mice. Food consumption was similar in both groups, but with a trend towards slightly higher intake (12%) in the lichen group. The heart, liver, kidney and lymphoid organ (spleen and thymus) weights were not affected by the lichen. Histological hematoxylin eosin staining showed that all these organs were normal. Plasma glucose levels were unchanged, but plasma urea levels decreased by 24% (p < 0.05) with the lichen diet. Red and white blood cells and the number of lymphoid cells in the thymus and spleen were normal. The activity of thymocytes and spleen T-lymphocytes were not affected by the lichen diet, but spontaneous cell-mediated cytotoxicity (NK cells) tended (n.s.) to increase and spleen B-lymphocyte activity increased by 40% (p < 0.05). This study shows that the lichen rock tripe has immune stimulating effects important for host defence reactions and can be used as food in survival situations without any adverse effects on the metabolism.

Animals↗

Dietary phosphorus and an inflammatory challenge affect performance and immune function of weanling pigs.

Ninety-six 3-wk-old pigs (6.3+/-0.12 kg initial BW) were allotted to one of eight treatments based on BW and litter origin to determine the effect of dietary phosphorus and an inflammatory challenge on performance and immune function. Four corn-soybean meal-based treatment diets were formulated to contain 0.16, 0.24, 0.32, or 0.40% available P. Monocalcium-dicalcium phosphate was used as the supplemental P source. The Ca:available P ratio was maintained at 2:1. To challenge the pigs, half of the pigs in each dietary treatment were injected i.m. with E. coli lipopolysaccharide (200 microg/kg of BW) on d 7 and 14. This resulted in a 2 x 4 factorial arrangement of treatments. Average daily gain for the 35-d study was increased linearly (P < 0.01) by increasing supplemental P. Average daily gain and ADFI were decreased (P < 0.05) by lipopolysaccharide injection. Serum P concentrations increased linearly (P < 0.01) with increasing supplemental P. Antibody titers to the injection of sheep red blood cells and ovalbumin on d 21 decreased linearly (P < 0.10) by increasing supplemental P. In vitro blastogenic response of lymphocytes to phytohemagglutinin (PHA) on d 25 was increased linearly (P < 0.05) by increasing supplemental P. Blastogenic response of lymphocytes to pokeweed mitogen on d 25 was not affected. On d 31, skinfold thickness 6 h following an intradermal injection of PHA was increased quadratically (P < 0.07) by increasing supplemental P. There were no P x lipopolysaccharide interactions for any immune response measure. In conclusion, increasing supplemental P increased ADG and enhanced cell-mediated immune response but decreased humoral immune response.

Animals↗

Therapeutic effect of cryosurgery of murine osteosarcoma--influence on disease outcome and immune function.

Experiments comparing conventional operative treatment and cryosurgery of a murine osteosarcoma showed that local tumor destruction by freezing in situ was similar or superior to amputation concerning survival and formation of metastasis, depending on tumor stage. Limited local resection was less effective. Immune functions affected by cryosurgical tumor destruction included depression of natural killer cell activity and decrease of tumor-specific autologous IgG antibodies in the serum.

Animals↗

[Effect of beneficial mixture for body immune function on serum acute phase reaction protein levels in acute traumatic patients].

The levels of acute phase reaction protein (ARP)--haptoglobin (HP), plasma albumin (Palb), transferrin (TF) and alpha-acid glycoprotein (alpha-AG), and the effect of Beneficial Mixture for Body Immune Function (BMBIF), were studied in 20 cases with acute injury. The results were shown that the metabolism of the protein of traumatic body was in disorder: the levels of HP and alpha-AG significantly increased, while the levels of Palb and TF obviously decreased. After the treatment of BMBIF, the ARP recovered to a certain extent. This proved that BMBIF could adjust the disorder of ARP metabolism.

Acute-Phase Proteins↗

Amino acid nutrition and immune function in tumour-bearing rats: a comparison of glutamine-, arginine- and ornithine 2-oxoglutarate-supplemented diets.

Dietary supplementation with glutamine (Gln), arginine (Arg) or ornithine 2-oxoglutarate (alpha-ketoglutarate; OKG) has attracted recent attention for the potential to improve anti-cancer immune function. However, since these compounds have not been compared systematically in an internally controlled study, their relative efficacy is difficult to estimate. Buffalo rats were fed on nutritionally complete semi-purified diets supplemented with Gln, Arg or OKG for 14 days after implantation of the Morris hepatoma 7777 (n>/=7 per diet). The control diet was made isonitrogenous and isoenergetic by addition of a mixture of non-essential amino acids. After 14 days, peritoneal macrophages and splenocytes were isolated to determine cell phenotypes, macrophage cytostatic activity and natural killer (NK) cell cytotoxicity, as well as nitric oxide (NO) and cytokine production. Diet had no effect on tumour weight (1.6+/-0.2 g; n=59). However, rats fed OKG had increased macrophage cytostatic activity and NK cell cytotoxicity (P<0.05). Although enhanced killing ability by NK cells was associated with higher splenocyte NO production (P<0.04), increased cytotoxicity was not inhibited by a specific inhibitor of inducible NO synthase. The proportion of interleukin-2-receptor-positive T cells after stimulation increased in rats fed OKG (P<0.05); however, cytokine production was not affected by diet. None of OKG, Gln or Arg altered tumour growth compared with a control mixture of non-essential amino acids. These results suggest no net advantage for anti-cancer immunity, but do not preclude benefits in immune responses to disease recurrence or metastasis, therapy or secondary infection.

Analysis of Variance↗

Psychosocial effects on immune function: neuroendocrine pathways.

Psychoneuroimmunology represents the newest interdisciplinary endeavor relevant to psychosomatic medicine. Work in this area is particularly exciting because it promises to reveal a more unified view of the individual and the complex interactions between social, psychological, neural, endocrinological, immunological, and genetic factors that contribute to disease. This article reviews the major biological pathways implicated in the psychosocial modulation of immune function and disease resistance.

Autonomic Nervous System↗

The relationship of interleukin-1 and immune functions to sleep in humans.

Serial sampling of peripheral blood from six healthy adult male volunteers was performed during daytime waking and nighttime sleeping. In addition, sleep physiology was assessed in all subjects (Ss) and sleep stages scored blind by standard criteria. Samples of plasma were analyzed for cortisol (Co) levels, functional interleukin-1 (IL-1), and interleukin-2 (IL-2) activity. Peripheral blood monocytes (PBM) were assayed to evaluate natural killer (NK) activity and mitogen responsiveness. Dramatic increase in IL-1 activity along with changes in other immune functions occurred during sleep and were related to onset of slow wave sleep.

Adult↗

The Qa-1 antigenic system. Relation of Qa-1 phenotypes to lymphocyte sets, mitogen responses, and immune functions.

The antiserum (B6 X A-Tlab) anti-A (Tlaa) defines several TL antigens expressed exclusively on thymocytes. When reacted with peripheral lymphocytes, the same antiserum defines another antigenic system, provisionally termed Qa-1. The genotypic disparity distinguishing the recipients and donors in this immunization comprises a section of chromosome 17 extending from a crossover point between H-2D and Tla to a presently unmarked point beyond Tla. Therefore although Qa-1 may constitute a single cell surface component, it is equally probable that the Qa-1 system defines two or more cell surface components determined by genes in this region, each of which may be expressed on a different cell set. Cytotoxicity assays indicate that Qa-1 antigen is expressed on Lyt-1 cells and Lyt-123 cells, and may serve to subclassify these two cell sets; it is not known whether Qa-1+ cells may occur within the small Lyt-23 set. There may be also be a cell set with the phenotype Thy-1--:Qa-1+. Another distinctive feature of the Qa-1 system is the characteristic profile of responses to mitogens exhibited by spleen cell populations from which Qa-1+ cells have been eliminated; in conventional assay of [3H]thymidine incorporation the response to lipopolysaccharide was essentially unchanged, the response to phytohemagglutinin M (PHA-M) was virtually abolished, and the response to concanavalin A (Con A) was reduced by 40%. The third distinctive feature of the Qa-1 system is the characteristic profile of changes which elimination of Qa-1+ cells produces in tests of immune function in vitro: (a) proliferation, measured by [3H]thymidine incorporation, in mixed lymphocyte culture (MLC) with major histocompatibility complex (MHC)-incompatible stimulator cells, was not affected. (b) in tests of cell-mediated cytotoxicity (CMC) of MHC-incompatible target cells, neither the generation nor the effector functions of cytotoxic lymphocytes was affected, implying that Lyt-23 prekiller and killer cells are Qa-1--. (c) primary and secondary responses to SRBC were considerably augmented, suggesting that Qa-1+ cells may be responsible for suppression in this test system. (d) accordingly the suppression of the anti-sheep erythrocyte (SRBC) response normally engendered in spleen cells by culture with SRBC was profoundly reduced by elimination of Qa-1+ cells, either before or after culture. (e) the suppression of the anti-SRBC response normally engendered in spleen cells cultured with Con A was reduced by removal of Qa-1+ cells before but not after culture with Con A. Although analysis is as yet far from complete, the Qa-1 system should already be of considerable value because it distinguishes a population of lymphocytes that is not defined by any other antigenic system, according to three criteria: (a) representation of Qa-1 cells among T-cell sets defined by Lyt phenotypes, (b) the profile of responses to mitogens exhibited by lymphocyte populations depleted of Qa-1+ cells, and (c) the profile of immune responses of lymphocyte populations depleted of Qa-1+ cells.

Animals↗

[Effects of drug cupping therapy on immune function in chronic asthmatic bronchitis patients during protracted period].

UNLABELLED: To observe the clinical effect of drug cupping therapy (DCT, cupping therapy with pingchuan ointment made by the authors themselves in the cups) on chronic asthmatic bronchitis (CAB) during the protracted period, and explore its effect on immune function. METHODS: Seventy-seven patients were randomly divided into two groups:the treated group (n=40) treated by orally taken Liuwei Dihuang Pill (LDP) and DCT and the control group (n=37) with LDP and common cupping therapy without drug in cups. The changes of T-lymphocyte subset, levels of interferon-gamma (IFN-gamma), interleukin (IL), immunoglobulin (Ig), complement 3 and 4 (C3 and C4) were detected before and after treatment. RESULTS: The total effective rate was higher in the treated group than that in the control group (90.0% vs. 59.5%, P < 0.01). The levels of CD4+, CD4+ /CD8+, IL-2, IFN-gamma, C3, C4, IgA, IgG and IgM increased, while the levels of IgE, IL-4, IL-10 and CD8+ decreased after treatment in both groups (P < 0.05 or P < 0.01), the improvements were better in the treated group than that in the control group (P < 0.05). CONCLUSION: DCT shows better curative effects than that of common cupping therapy without drug, it could improve the cellular and humoral immunity in CAB patients.

Adolescent↗

posttranslational modification of recombinant Plasmodium falciparum apical membrane antigen 1: impact on functional immune responses to a malaria vaccine candidate.

Recombinant apical membrane antigen 1 (AMA1) is a leading vaccine candidate for Plasmodium falciparum malaria, as antibodies against recombinant P. falciparum AMA1 (PfAMA1) interrupt merozoite invasion into erythrocytes. In order to investigate the role of posttranslational modification in modulating the functional immune response to recombinant AMA1, two separate alleles of PfAMA1 (FVO and 3D7), in which native N-glycosylation sites have been mutated, were produced using Escherichia coli and a Pichia pastoris expression system. Recombinant Pichia pastoris AMA1-FVO (PpAMA1-FVO) and PpAMA1-3D7 are O-linked glycosylated, and 45% of PpAMA1-3D7 is nicked, though all four recombinant molecules react with conformation-specific monoclonal antibodies. To address the immunological effect of O-linked glycosylation, we compared the immunogenicity of E. coli AMA1-FVO (EcAMA1-FVO) and PpAMA1-FVO antigens, since both molecules are intact. The effect of antigen nicking was then investigated by comparing the immunogenicity of EcAMA1-3D7 and PpAMA1-3D7. Our data demonstrate that there is no significant difference in the rabbit antibody titer elicited towards EcAMA1-FVO and PpAMA1-FVO or to EcAMA1-3D7 and PpAMA1-3D7. Furthermore, we have demonstrated that recombinant AMA1 (FVO or 3D7), whether expressed and refolded from E. coli or produced from the Pichia expression system, is equivalent and mimics the functionality of the native protein in in vitro growth inhibition assay experiments. We conclude that in the case of recombinant AMA1, the E. coli- and P. pastoris-derived antigens are immunologically and functionally equivalent and are unaffected by the posttranslational modification resulting from expression in these two systems.

Amino Acid Sequence↗

Growth hormone improves immune function and survival in burned mice infected with herpes simplex virus type 1.

Recombinant human growth hormone (rhGH) is often used clinically for the treatment of burned patients to promote wound healing and to improve protein metabolism. Recently, the immunomodulatory activity of GH has been described, but it remains unclear whether immune abnormalities associated with burn are improved by rhGH administration. To determine the immunoregulatory activities of rhGH in thermal injury, the survival of burned mice infected with herpes simplex virus type 1 (HSV-1), along with interferon-gamma (IFN-gamma) production by splenic mononuclear cells (SMNCs), and generation of cytostatic macrophages in burned mice were examined after exogenous administration of rhGH. Data showed that the mortality after HSV-1 infection was improved in burned mice treated with a 4-mg/kg dose of rhGH every other day for five doses. Also, the decreased IFN-gamma response of SMNCs from burned mice improved with rhGH therapy. Further, cytostatic macrophages were generated in burned mice treated with rhGH, whereas these macrophages were not demonstrated in burned mice treated with saline. These results indicate that rhGH can improve immune function in burned mice, specifically improving survival in HSV-1 infection, boltering IFN-gamma production by SMNCs, and increasing production of cytostatic macrophages.

Animals↗

Associations between altered immune function and organochlorine contamination in young Caspian terns (Sterna caspia) from Lake Huron, 1997-1999.

Previous studies of laboratory animals and wildlife species have demonstrated the immunotoxicity of organochlorines. This study confirmed that associations between organochlorines and suppressed T cell function and enhanced antibody production in young Caspian terns from the Great Lakes, first observed in the early 1990s, continued into the late 1990s. These associations were based on measurement of organochlorines in plasma of individuals and pooled egg samples. During 1997-99, immune function, hematological variables, and organochlorine contamination were measured in prefledgling Caspian terns at two Lake Huron colonies: Channel Shelter Island (Confined Disposal Facility) at the mouth of the Saginaw River in southern Saginaw Bay and Elm Island in the North Channel. Elevated organochlorine exposure, reproductive effects, and decreased recruitment have been documented previously in the Saginaw Bay colony. Concentrations of polychlorinated biphenyls (PCBs) in eggs and plasma and 1,1-dichloro-2,2-bis(p)chlorophenyl)ethylene (DDE) in plasma were consistently higher in Saginaw Bay compared to the North Channel. The mean phytohemagglutinin (PHA) skin test, a measure of T lymphocyte function, was 42% lower in Saginaw Bay. Regression analyses showed strong negative associations between the PHA response and plasma PCBs and, to a slightly lesser degree, DDE. Despite interyear differences, total antibody titers following immunization with sheep red blood cells were higher in Saginaw Bay than the North Channel. Titers were positively associated with plasma PCBs and DDE. Plasma PCBs and DDE were negatively correlated with the percentage of monocytes and positively correlated with the percentage of basophils.

Animals↗

Definition of a common leukocyte cell-surface antigen (Lp95-150) associated with diverse cell-mediated immune functions.

We have described a monoclonal antibody, designated 60.3, which reacts with a cell surface antigen expressed by most peripheral blood and bone marrow leukocytes. Immunoprecipitation showed at least three major components with relative m.w. of 95,000, 130,000, and 150,000 under reducing conditions. Antibody 60.3 inhibited several cell-mediated immune functions. The lytic activity of both cytotoxic T cells and natural killer cells was blocked in the presence of the antibody. The proliferative responses of T cells stimulated by soluble antigens, mitogens, or allogeneic cells were inhibited when antibody 60.3 was added at the initiation of culture, but not when added after 48 hr. Antibody 60.3 also blocked the migration of neutrophilic granulocytes. The antigen identified by antibody 60.3 thus appears to be involved in a membrane-dependent cell activation pathway that is common to diverse functional systems and is shared by both lymphoid and myeloid cells.

Animals↗

Effect of dietary chlorogenic acid on multiple immune functions and formation of aberrant crypt foci in rats.

Adult male Sprague-Dawley rats were fed 70 mg/kg body weight chlorogenic acid (CHA) for 7 wk. One CHA-fed group was also given 2 injections of the colon carcinogen azoxymethane (AZO) on d 2 and 9 of CHA treatment. Three major types of immune responses were assessed: antibody production, specific cell-mediated immunity, and nonspecific cell-mediated immunity. The formation of AZO-induced aberrant crypt foci (ACF) in the colon were observed, as was colonic cell proliferation. There were no significant effects of CHA treatment on any of the immune parameters examined or on formation of preneoplastic lesions or cell proliferation in the colon. The overall nonsignificant trends in immune function, colon cell proliferation, and ACF development were, however, more consistent with immunosuppression and enhanced preneoplasia.

Animals↗