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Small volumes of enteral feedings normalise immune function in infants receiving parenteral nutrition.

BACKGROUND/PURPOSE: Parenteral nutrition (PN) is associated with a risk of septicaemia. This may be caused by impairment of immune function related to PN. The authors investigated the effects of the addition of enteral feedings to PN on the immune status of human newborn infants. METHODS: Ten surgical infants (age less than 6 months) requiring PN were studied in two consecutive phases: (A) after 31.1+/-6.0 days (mean +/- SEM) of PN with no enteral feeding (total PN); and (B) after 4.7+/-1.1 days from the addition of small volumes of enteral feeding to PN. Full blood count and liver function tests were not significantly different between phases A and B. A control group (n = 9) of infants receiving a normal enteral diet was also studied. Host bactericidal activity against coagulase-negative staphylococci (CNS) was measured by an in vitro whole blood model. Bacterial killing was measured after a 45-minute bacterial challenge using the Miles-Misra technique. Tumour necrosis factor-alpha (TNF-alpha) was measured by enzyme-linked immunosorbent assay (ELISA) after 2 hours of bacterial challenge. RESULTS: The lowest level of CNS killing (37.7+/-5.2%), was observed in patients receiving total PN. This increased significantly after the addition of small enteral feeds (52.0+/-4.6%, P < .005) approaching the levels measured in controls (65.1+/-3.4%). TNF-alpha production was low during total PN (1467+/-297 pg/mL) and rose significantly after the addition of minimal enteral feeds (4,661+/-1,311 pg/mL, P < .05). The increase in CNS killing after the addition of small enteral feeds in patients on PN was significantly correlated with the duration of enteral feeding (r = 0.8, P = .006). CONCLUSIONS: These results indicate that the introduction of small volumes of enteral feed improve the impaired killing of CNS and the abnormal cytokine response observed during total PN. This implies that stimulation of the gastrointestinal tract may modulate immune function in neonates and prevent bacterial infection.

Bacteremia↗

[Effects of crowding on immune functions in mice].

The effects of several types of crowding on immune functions were studied in mice. This study consisted of two experiments. Experiment one: Male BALB/c mice were initially housed in groups of four mice per cage. After fourteen days of acclimation, the mice were randomly divided into three groups, Control (four mice per cage, control group), Crowd-I (four mice per small space) and Crowd-II (sixteen mice per cage). These conditions were maintained for seven days. The results of experiment one were as follows: (1) The percentage of lymphocytes in the blood of Crowd-II was significantly lower than that of Control (p < 0.05). (2) The percentage of neutrophils and the absolute number of neutrophils in blood of Crowd-II were significantly higher than in Control (p < 0.05). (3) Superoxide production activity (NBT reduction activity) of blood neutrophils in Crowd-II tended to be depressed, and phagocytic activity of neutrophils was significantly depressed in Crowd-II as compared with Control (p < 0.01). These results suggest that the complexity of interrelationships among mice caused by an increase in the number of animals per cage is a very important stress factor. Experiment two: Male BALB/c mice were initially housed in groups of five mice per cage. After fourteen days of acclimation, the mice were divided into three groups, Control (five mice per cage, control group), Crowd-(1) (five mice per cmall space) and Crowd-(2) (twenty mice per cage). In Control and Crowd-(1), the same mice were used as in the acclimation period. These conditions were maintained for seven days. In this period, on the second day, all the mice were injected intraperitoneally with sheep red blood cells (SRBC). The results of experiment two were as follows: (1) The specific humoral immune response to SRBC was investigated in terms of the number of PFC in the spleens and hemagglutination in sera, but significant differences were not found among the groups. (2) Plasma IgG levels in the Crowd-(1) were significantly higher than those in Control (p < 0.05). (3) Both superoxide production activity and phagocytic activity of neutrophils were significantly depressed in Crowd-(2) as compared with Control (p < 0.01, respectively), whereas each neutrophil function of Crowd-(1) tended to be enhanced as compared with Control.

Animals↗

Immune function in ankylosing spondylitis: apparent relationship between streptococcal responses and HLA B27.

Immune function has been evaluated in 54 patients with ankylosing spondylitis (AS) and 26 controls. Cell-mediated immunity was assessed by skin testing with ubiquitous antigens, and humoral immunity by antibody responses to tetanus toxoid and Salmonella typhi vaccinations, and resting titres of anti-Streptolysin O, anti-E Coli, and isohemagglutinins. The AS patients had reduced delayed hypersensitivity responses to Candida, augmented responses to Streptococcal antigen and relatively low ASO titres. There was no generalized depression of humoral immunity, as indicated by the normal tetanus and Salmonella O responses and hyper-response to Salmonella H antigen. The E. Coli and isohemagglutinin titres were normal. These results indicate that patients with AS present a complex immunological profile, including exaggerated responses to some antigens and impaired responses to others. In view of the very high incidence of HLA-B27 in AS, it is possible that these findings are related to the effects of HLA associated immune response genes.

Adult↗

Postgrafting administration of granulocyte colony-stimulating factor impairs functional immune recovery in recipients of human leukocyte antigen haplotype-mismatched hematopoietic transplants.

In human leukocyte antigen haplotype-mismatched transplantation, extensive T-cell depletion prevents graft-versus-host disease (GVHD) but delays immune recovery. Granulocyte colony-stimulating factor (G-CSF) is given to donors to mobilize stem cells and to recipients to ensure engraftment. Studies have shown that G-CSF promotes T-helper (Th)-2 immune deviation which, unlike Th1 responses, does not protect against intracellular pathogens and fungi. The effect of administration of G-CSF to recipients of mismatched hematopoietic transplants with respect to transplantation outcome and functional immune recovery was investigated. In 43 patients with acute leukemia who received G-CSF after transplantation, the engraftment rate was 95%. However, the patients had a long-lasting type 2 immune reactivity, ie, Th2-inducing dendritic cells not producing interleukin 12 (IL-12) and high frequencies of IL-4- and IL-10-producing CD4(+) cells not expressing the IL-12 receptor beta(2) chain. Similar immune reactivity patterns were observed on exposure of donor cells to G-CSF. Elimination of postgrafting administration of G-CSF in a subsequent series of 36 patients with acute leukemia, while not adversely affecting engraftment rate (93%), resulted in the anticipated appearance of IL-12-producing dendritic cells (1-3 months after transplantation versus > 12 months in transplant recipients given G-CSF), of CD4(+) cells of a mixed Th0/Th1 phenotype, and of antifungal T-cell reactivity in vitro. Moreover, CD4(+) cell counts increased in significantly less time. Finally, elimination of G-CSF-mediated immune suppression did not significantly increase the incidence of GVHD (< 15%). Thus, this study found that administration of G-CSF to recipients of T-cell-depleted hematopoietic transplants was associated with abnormal antigen-presenting cell functions and T-cell reactivity. Elimination of postgrafting administration of G-CSF prevented immune dysregulation and accelerated functional immune recovery.

Acute Disease↗

[The effect of a vaccine made from 39kd hydrophobic outer membrane protein of Leptospira interrogans on neurohumoral and red cell immunity function of the guinea pigs].

A randomized control trial was conducted to determine the immunoprotective efficacy of OmpL39. 36 guinea pigs were divided into OmpL39 group, whole leptospiral cell vaccine (WLCV) group, other proteins of Leptospira group, and negative control group (normal saline, NS). The results showed that all the guinea pigs of infected OmpL39 and WLCV still survived, but all the control guinea pigs died. Immunoprotective efficacy was 100% for OmpL39 and WLCV. OmpL39 levels were similar to WLCV levels and higher than controls (P < 0.05). These suggested that OmpL39 could be used as important immunoprotective antigen to develop the genetic vaccine of the targeting delivery system. Also it was observed that OmpL39 could produce 100% immunoprotective efficacy, have higher MAT level (> 1:3200) and regulate 5-HT, 5-HIAA, DA, NE. The 5-HT, DA, NE concentration was lower and 5-HIAA was higher than that of controls after stimulating the guinea pigs with OmpL39 (P < 0.05). The results suggested that OmpL39 genetic vaccine could produce immunity function and have an active effect on absorbing inflammation and protecting organs and tissues. Besides, the red cell immunity efficacy of the guinea pigs was changed during immunity response and the RBC-C3b RR and the RBC-ICR were increased. The RFER was increased; the RFIR was decreased. RFER/RFIR was remarkably higher than that of control (P < 0.05). These suggested that OmpL39 could increase red cell immunity function.

Animals↗

Enhancing versus suppressive effects of stress hormones on skin immune function.

Delayed-type hypersensitivity (DTH) reactions are antigen-specific cell-mediated immune responses that, depending on the antigen, mediate beneficial (e.g., resistance to viruses, bacteria, and fungi) or harmful (e.g., allergic dermatitis and autoimmunity) aspects of immune function. Contrary to the idea that stress suppresses immunity, we have reported that short-duration stressors significantly enhance skin DTH and that a stress-induced trafficking of leukocytes to the skin may mediate this immunoenhancement. Here, we identify the hormonal mediators of a stress-induced enhancement of skin immunity. Adrenalectomy, which eliminates the glucocorticoid and epinephrine stress response, eliminated the stress-induced enhancement of skin DTH. Low-dose corticosterone or epinephrine administration significantly enhanced skin DTH and produced a significant increase in the number of T cells in lymph nodes draining the site of the DTH reaction. In contrast, high-dose corticosterone, chronic corticosterone, or low-dose dexamethasone administration significantly suppressed skin DTH. These results suggest a role for adrenal stress hormones as endogenous immunoenhancing agents. These results also show that hormones released during an acute stress response may help prepare the immune system for potential challenges (e.g., wounding or infection) for which stress perception by the brain may serve as an early warning signal.

Adrenalectomy↗

Sex-dependent association between immune function and paw preference in two substrains of C3H mice.

Asymmetry in brain modulation of the immune system has been previously described in mice. Paw preference is known to be associated with immune reactivity but the respective roles of sex and genetic background in this association remain to be elucidated. In this work, male and female mice of the C3H/He and C3H/OuJIco substrains were selected as right- and left-handers. Mitogen-induced lymphoproliferation and natural killer cell activity were then tested. Left-handed female mice of both C3H substrains exhibited higher mitogenesis than right-handers but no association between paw preference and NK cell activity was found in females. Conversely, in males of both substrains, right-handers showed enhanced NK cell activity compared to left-handers but no association between paw preference and mitogenesis was observed in males. Only small differences in the strength, but not in the direction, of the association between paw preference and immune functions were observed between the two C3H substrains. These results show that the association between paw preference and immune reactivity in mice varies according to the immune parameters tested and is a sex-dependent phenomenon in which the genetic background may be involved.

Animals↗

Suppression of immune function by non-peptidic delta opioid receptor antagonists.

Previous studies in this laboratory and elsewhere have provided evidence that compounds acting as delta opioid receptor agonists exhibit marked immunostimulatory potential. Conversely, the delta opioid receptor antagonists have previously been shown to demonstrate immunosuppressive effects as assessed by proliferation of T-cells following allogeneic or xenogeneic stimulation. The present study was performed to further characterize this immunosuppressive activity using the compounds benzylidene naltrexone (BNTX), naltrindole (NTI), and naltriben (NTB). In vitro exposure to BNTX resulted in an apparent dose-related suppression of B-cell proliferation, cytokine production by T-helper cells, and natural killer (NK) cell activity, with statistically significant suppression observed at concentrations between 1 and 10 microM. NTI was also immunosuppressive for all immune function parameters examined, although this compound was less active than BNTX. In vitro exposure to the structurally related compound NTB had no significant effect on any immune function examined in this study. In all cases, immunosuppression occurred in the absence of any detectable alteration in cellular viability, suggesting a specific immunosuppressive effect rather than overt toxicity.

Animals↗

Cyclophosphamide effects on immune function of European starlings.

We developed and tested a battery of immune function assays on adult European starlings (Sturnus vulgaris) exposed to the immunotoxicant cyclophosphamide (CY). Starlings were injected intraperitoneally for three consecutive days with saline or 20 mg/kg CY. Cyclophosphamide did not affect body mass or packed cell volume. However, spleen to body mass ratios and the number of viable spleen cells were lower in CY-treated birds when compared to controls. Peripheral white blood cell numbers were reduced in CY-treated starlings, and the decrease affected all cell types. Phagocytic ability of macrophages cultured from peripheral blood monocytes was impaired in cells from CY-treated birds. Additionally, CY treatment resulted in decreased lymphocyte blastogenesis to the T-cell mitogen Concanavalin A. The hemagglutination response to sheep erythrocytes was lower in birds that had received CY. Thus, these immunological methods detected chemically-induced immune dysfunction in starlings.

Animals↗

Cancer, immune function, and physical activity.

Despite the problems of interpreting epidemiological studies and the difficulty in developing appropriate animal models, there is growing evidence that moderate habitual physical activity can protect against certain types of neoplasm, particularly tumors of the colon and the female reproductive tract. Exercise programs also appear to have a beneficial influence on clinical course, at least in the early stages of the disease. Recent demonstration of exercise-induced changes in the activity of macrophages, natural killer cells, lymphokine activated killer cells, neutrophils, and regulating cytokines suggest that immuno-modulation may contribute to the protective value of exercise. Depression of immune function, such as in HIV infection and in old age, is associated with an enhanced susceptibility to tumors; but the sites of tumorigenesis in HIV infection are not those that gain protection from physical activity. Further research is thus needed before it can be asserted that favorable exercise-induced changes in immune function have a material influence on the risks posed by various types of cancer.

Aged↗

Life events, depressive symptoms, and immune function.

Because both bereavement and depression have been associated with impaired immune responses, the authors studied two indicators of immune function, natural killer (NK) cell activity and measures of T cell subpopulations, in 37 women who differed in the magnitude of recent life events. Women who had experienced major life changes had lower NK cell activity than women who had few changes. Severity of depressive symptoms in these women was associated with an impairment of NK cell activity, an absolute loss of suppressor/cytotoxic cells, and an increase in the ratio of T helper to T suppressor/cytotoxic cells.

Adult↗

Immune functions in splenectomized thalassaemic children.

A prospective study to assess the immune functions in splenectomized thalassaemic children. Children were those registered in the Thalassemia major. There were 10 splenectomized children (Group 1), 10 non-splenectomized children and 6 age-matched control (Group 3). All children were shown to be HIV seronegative. The mean concentrations of serum IgG and IgA were higher in Group 1 as compared to Groups 2 and 3 but the differences were not statistically significant. Nitroblue tetrazolium (NBT) dye reduction by stimulated polymorphonuclear leukocytes was normal in both study and control groups and the differences were not statistically significant. However, NBT reduction in the unstimulated state was much higher in Group 2 as compared to Groups 1 and 3. Phytohaemagglutinin induced mitogen proliferation was normal in all 3 groups. Children in Group 1 not only had a significantly higher absolute lymphocyte count but also had a lower CD4/CD8 ratio as compared to Groups 2 and 3. Splenectomy does appear to alter the immune status of thalassemic children but the exact mechanism by which this occurrence is not clear.

Child↗

Time-course of the recovery of cellular immune function after high-dose chemotherapy and peripheral blood progenitor cell transplantation for high-grade non-Hodgkin's lymphoma.

Chemotherapy induces high remission rates in high-grade lymphoma. However relapse remains a major problem. One approach to this is myeloablative chemotherapy with transplantation of autologous bone marrow or peripheral blood progenitor cells (PBPC). Immunological mechanisms have been suggested to play a role in the prevention of relapse after transplantation. We investigated the recovery of cellular immune functions after high-dose chemotherapy and PBPC transplantation in 5 patients with high grade non-Hodgkin's lymphoma. All patients showed rapid reconstitution of natural killer (NK) and inducible lymphokine-activated killer (LAK)-activity 10-14 days after transplantation. Four of 5 patients showed higher levels of LAK-generation in the post-transplant period compared with levels prior to myeloablative treatment. Absolute lymphocyte counts in peripheral blood reached 1.0 x 10(9)/l between days 10 and 13 with a predominance of CD8+ cells and an inversion of the CD4/CD8 ratio. Four of 5 patients had a transient increase in CD56+ and CD16+ cell counts post-transplant. No change in the proportion of CD25+ cells was noted. These results show that PBPC transplantation leads to a rapid recovery of cellular immune functions after myeloablative chemotherapy and provides evidence for an increased presence of LAK precursor cells early in the post-transplant period which can be activated by IL-2 to exert high levels of cytotoxicity.

Adolescent↗

Human monoclonal antibodies heterogeneously express a human cross-reactive idiotype associated with immune function in Schistosoma japonicum infection.

Hybridomas secreting human monoclonal antibodies (hMAb) were derived from Epstein Barr Virus (EBV) transformed lymphocytes of a patient with acute Schistosoma japonicum infection. Three IgG1 hMAb SJ-D, SJ-E, and SJ-F bind soluble egg antigens (SEA) as determined by ELISA. These hMAb exhibit identical western blot profiles, recognizing an epitope(s) of multiple antigens with apparent molecular weights between 42 and 75 kDa. Serological analysis of these hMAb revealed a heterogeneity in their expression of a specific human S. japonicum anti-SEA associated cross reactive idiotype designated Hu SJ-CRIM. The differential expression of idiotypy by these hMAb correlates with immunosuppression of blastogenesis of lymphocytes from schistosomiasis patients. The level of suppression mediated by hMAb expressing high levels of Hu SJ-CRIM ranged from 41% to 52% (p < 0.05) for antigen and 36% to 43% for mitogen. In contrast, hMAb SJ-D which expressed over two fold lower levels Hu SR-CRIM, on a per weight basis showed no suppressive immune function. The data show the heterogeneous expression of human idiotype associated with S. japonicum infection and the correlation of idiotype expression with immune function.

Animals↗

Cow's milk and type 1 diabetes: the real debate is about mucosal immune function.

The hypothesis that early exposure of the infant to cow's milk (or lack of breast-feeding) predisposes the child to type 1 diabetes dates from the 1980s. It has important implications, but remains controversial because the evidence on which it is based has been indirect and is open to criticism. Two meta-analyses of multiple studies in which diabetes prevalence was associated retrospectively with infant feeding revealed only a marginal increase in relative risk. Two recent prospective studies found no apparent association between development of antibodies to islet antigens and feeding patterns in high-risk infants with a first-degree type 1 diabetic relative. Studies reporting increased humoral and cellular immunity to cow's milk proteins in children with type 1 diabetes often lack appropriate controls and standardization and do not, in themselves, establish a causal connection to disease pathogenesis. A review of published data leads to the conclusion that increased immunity to cow's milk proteins is not disease-specific, but reflects genetic predisposition to increased immunity to dietary proteins in general, associated with the HLA haplotype A1-B8-DR3-DQ2 (A1*0501, B1*0201), which also predisposes to celiac disease and selective IgA deficiency. We suggest that the cow's milk hypothesis could be productively reframed around mucosal immune function in type 1 diabetes. Breast milk contains growth factors, cytokines, and other immunomodulatory agents that promote functional maturation of intestinal mucosal tissues. In the NOD mouse model, environmental cleanliness may influence diabetes incidence through mucosal mechanisms, and exposure of the mucosa to insulin (present in breast milk) induces regulatory T-cells and decreases diabetes incidence. The mucosa is a major immunoregulatory barrier, and cow's milk happens to be the first dietary protein it encounters. The basic question is whether impaired mucosal immune function predisposes to type 1 diabetes.

Animals↗

The effects of stress on splenic immune function are mediated by the splenic nerve.

Intermittent footshock (FS) suppresses immune function of spleen cells. To determine if the autonomic nervous system mediates this immunosuppression in spleen cells, we tested whether cutting the splenic nerve, which depletes splenic norepinephrine levels by 98-100% and eliminates catecholamine fibers, blocks the effects of stress. Splenic nerve sections, sham operations, or no surgery were performed on male Sprague-Dawley rats. Ten days later, rats were injected with sheep red blood cells (SRBC). Three days later, rats were placed in a chamber equipped with a shock grid. Foot shock (1.6 mA) was administered for 5 s on a VI 3.5 min schedule for 60 min. Each FS was preceded by a 15-s warning tone. Controls were treated identically except for the FS. The next day spleen cells were harvested and the number of IgM plaque-forming cells (PFCs) determined. For the sham and unoperated control animals, the number of PFCs was reduced for the stressed animals relative to the nonstressed controls, and there was no effect of the sham surgeries. In contrast, there was no difference between the stressed and nonstressed groups in which the splenic nerve had been sectioned, and their PFC response was comparable to the controls. Next we examined the effects of FS on the proliferative response to mitogens (PHA and ConA) following splenic nerve sections or sham operations. One week following surgery, animals were given a 60-min session of FS or exposed to the chamber/tone without FS. Rats were then killed, spleens harvested, and the proliferative response to mitogens determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Disorders of immune function in children with selective IgA deficiency].

Numerous additional alterations of immune function in patients with selective IgA deficiency (serum IgA less than 0.05 g/l) have been described. In this group of patients we have investigated the connection with allergic diseases and alterations of the other immunoglobulin isotypes. Sera of 44 children from 1 3/12 to 18 years were analysed. In all patients serum IgA was below the nephelometric detection limit of 0.05 g/l). Using a more sensitive ELISA, IgA could be detected in all sera in concentrations ranging from 10 micrograms/l to 0.04 g/l. 25 children (57%) revealed a profound elevation of IgG serum levels, in 27 (61%) IgM was elevated above the upper age related normal value. In 7 patients (16%) with normal IgG serum levels a combined IgG2-IgG4 deficiency was found. In most cases these patients had unusually frequent and severe infections. Total IgE serum levels were determined by a RIA technique. In addition, an IgE-mediated sensitization to the most common food and inhalation antigens was detected by a standardized procedure (Phadiatop, Pharmacia). In 9/44 children (20%) IgE was less than 2 U/ml (lowest detection limit), 27 patients (62%) revealed levels of 6-86 U/ml within the age-related normal range. In 8 patients (18%) total IgE was above 381 U/ml. Four patients demonstrated a sensitization to inhalants, specific IgE antibodies to nutritive antigens were detected in three children.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Immune function of cancer patients with spleen-deficiency syndrome].

According to this study, the immunological function was aberrant in cancer patients with Spleen-deficiency syndrome. The TII cell in normal persons (n = 26) was 30, 86 +/- 9.70% (means +/- S) and in these cases (n = 43) was 22.62 +/- 9.92%, P less than 0.002. The cytotoxicity of NK cell in patients (n = 59) was 17.65 +/- 10.58%, in normal controls (n = 43) was 25.51 +/- 14.10%. The combining ability of NK cell in patients (n = 48) was 39.11 +/- 19.43%, the normal persons (n = 41) was 55.88 +/- 17.94%. It showed that the immune function of the cancer patients with Spleen-deficiency syndrome were markedly lower than that of normal persons. The serum IgA in saliva of patients (n = 37) was 0.44 +/- 0.17 microgram/ml. It was much higher than that of normals' (n = 24, 0.30 +/- 0.06 microgram/ml), P less than 0.001. Some patients' NK cell function and the level of level of SIgA in saliva were recovered to normal after treatment of Shengxue Tang which could strengthen the Spleen and replenish the Kidney. These studies proved that the TCM played an important role for modulating immune function in treating cancer patients.

Adult↗