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At least 1,063 records · Page 59Linked to original sources
PubMed1997

Regulation of uterine immune function during the estrous cycle and in response to infectious bacteria in sheep.

Uterine infections are a major reproductive problem in livestock. We conducted two experiments to investigate factors that may modulate uterine responses to infectious bacteria. In Exp. 1, ewes received intrauterine inoculations of either saline or bacteria (75 x 10(7) cfu of Actinomyces pyogenes and 35 x 10(7) cfu of Escherichia coli) on either d 0 or 7 of the estrous cycle. Vena caval samples containing uteroovarian blood were collected twice daily from 12 h before until 6 d after inoculation. Only ewes inoculated with bacteria on d 7 developed infections. Basal (4.8 vs .4 pmol), lipopolysaccharide-stimulated (14.2 vs 6.1 pmol), and concanavalin A-stimulated (65.8 vs 21.6 pmol) blastogenesis (i.e., [3H]thymidine incorporation) of vena caval lymphocytes was greater (P < or = .002) for ewes inoculated with bacteria or saline on d 0 rather than on d 7. The number (per 100 white blood cells) of lymphocytes was greater (41.3 vs 30.8, P < .001) and that of neutrophils was less (42.5 vs 51.6, P < .001) in ewes inoculated on d 0 rather than d 7. Bacteria increased (P < .05) vena caval PGF(2 alpha) but not PGE2 concentrations. In Exp. 2, two protein fractions (molecular weights of > or = 100 kDa and approximately 12.7 kDa) from chromatography of uterine flushings collected on d 0 or 7, or 18 d after ovariectomy on d 0 or 7, modulated phytohemagglutinin-stimulated blastogenesis; the heavier fraction from d 0 had a stimulatory component, but the major effects of the fractions were inhibitory. The differences in immune function and regulation between d 0 and 7 probably explain how the uterus of follicular phase ewes was able to prevent the development of an infection.

Actinomyces↗
PubMed2004

Nutritional formula enhanced immune function and reduced days of symptoms of upper respiratory tract infection in seniors.

OBJECTIVES: To assess whether an experimental nutritional formula, given as a supplement, would reduce days of symptoms of upper respiratory tract infection (URTI) and affect antibody and lymphocyte proliferative responses to influenza vaccine. DESIGN: A prospective, randomized, double-blind, controlled trial was conducted between October 1999 and April 2000. SETTING: Assisted- and independent-living facilities in North Central Florida. PARTICIPANTS: Sixty-six individuals, aged 65 and older. INTERVENTION: Subjects received 8 oz/d of an experimental formula containing antioxidants, zinc, selenium, fermentable oligosaccharides, and structured triacylglycerol or an isoenergetic, isonitrogenous control formula for 183 days. MEASUREMENTS: Subjects recorded daily symptoms of URTI. Antibody titers and lymphocyte proliferation to three influenza vaccine components were measured on Days 57 and 183. RESULTS: Eighteen subjects in the control group and 16 subjects in the experimental group consumed an average of 7 ounces of formula daily and completed the 183-day study. Median days of symptoms of URTI were 3 (range 0-69, total days=156) and 0 (range 0-49, total days=78) for the control and experimental groups, respectively (P=.049). On Day 57, seven of 17 (41%) subjects in the control group and 13 of 15 (87%) subjects in the experimental group achieved a fourfold or greater increase in serum antibody titer to A/Beijing (P=.012). Lymphocyte proliferation to influenza vaccine components was greater in the experimental (median=1,365 cpm, range=0-14,955 cpm) than the control group (median=136 cpm, range=0-4,270 cpm) (P=.013). CONCLUSION: Subjects consuming an experimental nutritional formula experienced enhanced immune function and fewer days of URTI symptoms.

Aged↗
PubMed2000

Normal immune function in young and old DNA polymerase-beta deficient mice.

The effect of the DNA polymerase-beta (beta-pol) deficiency on mitogenic response and cytokine production was studied in spleen lymphocytes from 4-5- and 20-22-month-old beta-pol(-/+) mice and their age-matched wild-type littermates. The proliferative response of lymphocytes to Concanavalin A (Con A) and lipopolysaccharide (LPS) was measured by [3H]thymidine incorporation, and the induction of cytokine production (interleukin (IL)-2, IL-4, and interferon necrosis factor (IFN)-gamma) was assessed by enzyme-linked immunosorbent assay. There was no significant difference in Con A- or LPS-induced proliferation or cytokine production in young beta-pol(-/+) mice compared with young wild-type littermates or in old beta-pol(-/+) mice compared with old wild-type littermates. However, mitogen-induced proliferation and cytokine production changed significantly with age. The proliferative response to Con A and to LPS, and the IL-2 production was significantly lower, and IL-4 and IFN-gamma levels were significantly higher in lymphocytes from old beta-pol(-/+) mice and old wild-type mice than in lymphocytes from young beta-pol(-/+) mice and young wild-type littermates. In addition, flow cytometric analysis showed no significant differences between young beta-pol(-/+) mice and young wild-type littermates or between old beta-pol(-/+) mice and old wild-type littermates in the proportion of B- and T-cell populations, and T-cell subsets. However, the number of lymphocytes expressing CD4+ phenotype slightly decreased and the proportion of lymphocytes expressing CD44/Pgp-1 (memory) phenotype increased with age. Thus, we found no evidence for alteration in immune function in DNA polymerase-beta deficient mice, although they exhibit a decline in immunologic function with age.

Aging↗
PubMed1999

Peptides derived from ICAM-1 and LFA-1 modulate T cell adhesion and immune function in a mixed lymphocyte culture.

BACKGROUND: The counter receptors intercellular adhesion molecule (ICAM)-1 and lymphocyte function-associated antigen (LFA)-1 are lymphocyte cell surface adhesion proteins the interaction of which can provide signals for T cell activation. This binding event is important in T cell function, migration, and general immune system regulation. The ability to inhibit this interaction with monoclonal antibodies has proved to be therapeutically useful for several allograft rejection and autoimmune disease models. METHODS: Short peptides representing counter-receptor contact domains of LFA-1 and ICAM-1 were examined for their ability to inhibit T cell adhesion and T cell function. RESULTS: Peptides encompassing amino acids Q1-C21 and D26-K50 of ICAM-1, I237-I261 and G441-G466 of the LFA-1 alpha-subunit, and D134-Q159 of the LFA-1 beta-subunit inhibited LFA-1/ICAM-1-dependent adhesion in a phorbol-12,13-dibutyrate-induced model of tonsil T cell homotypic adhesion. This inhibition was specific to the peptide sequence and occurred without stimulation of T cell proliferation. The peptides also were effective in preventing T cell function using a one-way mixed lymphocyte reaction model for bone marrow transplantation. CONCLUSIONS: Our data suggest that these peptides or their derivatives may be useful as therapeutic modulators of LFA-1/ICAM-1 interaction during organ transplants.

Animals↗
PubMed2003

Immune function in children with classical phenylketonuria and tetrahydrobiopterin deficiencies.

BACKGROUND: An increased susceptibility to infections has been observed in some patients with phenylketonuria (PKU), which is not well known whether it is due to alterations of plasma essential amino acid concentrations or to some other factors. OBJECTIVE: This study is designed to establish B cell and T cell functions in 44 children with classical PKU and tetrahydrobiopterin (BH4) deficiencies and the effects of too high plasma phenylalanine (PA) concentrations (16.53 to 30.54 mg/dL) on the same parameters. DESIGN: B and T cell functions of 33 children with classical PKU (divided into two groups based on fasting mean plasma PA concentrations: Group-I = 20.9 +/- 3.7 mg/dL, Group-II = 3.8 +/- 1.02 mg/dL), and 11 children with BH4 deficiencies (Group III) were studied. The results were compared between the groups and referenced with previously reported values from healthy controls. RESULT: Delayed type skin hypersensitivity responses to purified protein derivative (PPD) in Group I and phytohaemagglutinin (PHA) in Group I, III were lower than the other groups and healthy controls. Plasma IgG and IgM concentrations of Group I was lower than the reference values. Although mean serum zinc and iron levels of all patients were lower than published values of healthy children, zinc and iron deficiencies in Group I, III were much more prominent as compared to Group II. CONCLUSION: The somewhat low plasma IgG concentrations in Group I may be related to the very high plasma PA levels, however the role of zinc deficiency as a causal factor can not be ruled out. BH4 metabolism defects do not appear to affect the same parameters. Impaired delayed skin hypersensitivity responses in Group I and III can be explained by severe serum zinc deficiency. In the light of this study, we conclude that in order to establish a causal relationship between PKU and immune functions, further studies need to be conducted after the correction of micro-nutrient status of such children.

B-Lymphocytes↗
PubMed2001

Influence of aminosteroid and glucocorticoid treatment on inflammation and immune function during cardiopulmonary bypass.

OBJECTIVE: During cardiopulmonary bypass, inflammation and immunosuppression is present. We measured circulating mediators and monocyte-based functions and tested the hypothesis that these variables are influenced by methylprednisolone (MP) or tirilazad mesylate (TM) treatment. DESIGN: Randomized, controlled, double-blind prospective trial. SETTING: A university hospital. PATIENTS: Thirty-nine patients scheduled for conventional coronary surgery with three-vessel disease. INTERVENTIONS: Preoperative application of MP (15 mg/kg) or TM (10 mg/kg) compared with placebo (PL). MEASUREMENTS AND MAIN RESULTS: Circulating proinflammatory markers including interleukin (IL)-6, IL-8, monocyte chemoattractant protein 1, and C-reactive protein were all decreased by MP treatment but not by TM treatment. Whereas rapid increases in circulating anti-inflammatory IL-10 were superinduced by MP but not TM, plasma levels of IL-1RA and transforming growth factor beta were not altered by either treatment. Decreased ex vivo lipopolysaccharide-stimulated secretion of tumor necrosis factor alpha was prolonged after MP treatment but not after TM treatment. Perioperative stimulated secretion of IL-12 and interferon gamma was diminished in all groups, whereas ex vivo IL-1RA secretion tended to increase in all groups. Depression of monocyte surface expression of HLA-DR was significantly greater in patients treated with MP, whereas CD14 expression did not change. CONCLUSIONS: These data confirm that, during cardiopulmonary bypass, pro- and anti-inflammatory systems are activated at the same time, whereas monocyte-based immune functions are depressed. Treatment with MP abrogates proinflammatory mediators and induces a shift toward anti-inflammation at the cost of further functional monocyte deficits, whereas treatment with TM apparently has neither anti-inflammatory nor immunosuppressive actions in this setting.

Antioxidants↗
PubMed2002

Serum alpha-tocopherol and immune function in yearling ewes supplemented with zinc and vitamin E.

Yearling Targhee ewes (n = 24; not pregnant or lactating) were used in a 2 x 2 factorial arrangement of treatments to determine the effects of supplemental vitamin E (0 IU [0vitE] vs 330 IU vitamin E x ewe(-1) x d(-1) [+vitE]) and Zn (0 mg [0Zn] vs 140 mg Zn x ewe(-1) x d(-1) [+Zn]) on serum alpha-tocopherol concentrations, antibodies to parainfluenza type 3 (PI3), ewe BW, Zn liver concentrations, and serum alkaline phosphatase activity. Ewes were managed as one group, grazed native pasture, and had ad libitum access to white salt and water. Ewes that received supplemental vitamin E were orally dosed every other day with 660 IU of DL-alpha-tocopherol acetate in a gelatin capsule beginning on d 1 and continuing to d 63 of the study. Ewes that received Zn supplement were orally dosed every other day with 280 mg of Availa-Zn 100 (Zinpro Corp., Eden Prairie, MN, IFN 6-32-054) in gelatin capsules for 63 d. All ewes were vaccinated with killed PI3 on d 22 and 42. No interactions were detected (P > 0.35); however, serum alpha-tocopherol concentrations and PI3 antibody titer dilutions changed (P = 0.001) over the length of the study. Ewe BW change, serum alkaline phosphatase activity, and liver Zn concentrations did not differ (P > 0.22) between 0Zn and +Zn or 0vitE and +vitE ewes. Serum a-tocopherol tended to be higher (P = 0.08) in +vitE than 0vitE ewes and was numerically higher (P = 0.16) in +Zn than 0Zn ewes. Antibody titer dilutions were higher (P = 0.06) in 0Zn than +Zn ewes and did not differ (P = 0.83) between 0vitE and +vitE ewes. These results indicate that high levels of supplemental Zn may have a tendency to improve serum alpha-tocopherol concentrations but may have negative impacts on humoral immune function.

Administration, Oral↗
PubMed1997

Testosterone receptor blockade after hemorrhage in males. Restoration of the depressed immune functions and improved survival following subsequent sepsis.

BACKGROUND: Recent studies suggest that androgen depletion by castration before hemorrhage has protective effects on cell-mediated immunity in male mice after soft tissue trauma and hemorrhagic shock. OBJECTIVE: To determine whether treatment with an androgen receptor blocker (eg, flutamide) after trauma-hemorrhage and sepsis has any salutary effects on cell-mediated immunity and on the survival of male animals under those conditions. DESIGN: Male C3H/HeN mice were either sham operated or subjected to hemorrhagic shock (mean [+/- SEM] blood pressure, 35 +/- 5 mm Hg for 90 minutes) followed by adequate fluid resuscitation (with shed blood and lactated Ringer solution). The animals then received either vehicle or 25-mg/kg body weight flutamide subcutaneously immediately after the resuscitation as well as 24 and 48 hours thereafter. At 48 hours after shock, sepsis was induced by cecal ligation and puncture. Sham-operated animals underwent laparotomy only. At 24 hours after cecal ligation and puncture, the animals were killed, blood was collected, and splenocytes and splenic macrophages were harvested to produce nonadherent and adherent cultures. Splenocytes were evaluated for splenocyte proliferation and interleukin 2 release, while interleukin 1 and interleukin 6 release were assayed in splenic macrophages. Plasma testosterone and corticosterone levels were also measured by radioimmunoassay. In a separate set of experiments, survival was measured over a period of 9 days after the induction of sepsis. RESULTS: Hemorrhage followed by sepsis produced a significant (P < .05) depression of splenocyte and macrophage functions in vehicle-treated animals. In contrast, animals treated with flutamide showed markedly improved immune functions, as evidenced by restoration of splenocyte proliferation, interleukin 2 release, splenic macrophage interleukin 1 release, and improvement of splenic macrophage interleukin 6 release. Plasma corticosterone levels were notably elevated while testosterone levels were depressed after hemorrhage and the induction of sepsis. The survival rate of the animals in the flutamide-treated group was also notably higher than the survival rate of animals in the vehicle-treated group subjected to hemorrhage and sepsis. CONCLUSION: The findings that flutamide not only markedly improves the depressed immune functions but also the survival of animals after hemorrhage and the induction of sepsis suggest that the short-term administration of androgen receptor blocker in males after trauma represents a safe and novel approach for preventing immune deficiency and decreasing the mortality rate from subsequent sepsis.

Androgen Antagonists↗
PubMed2006

Cell mediated immunity (CMI) and post transplant viral infections--role of a functional immune assay to titrate immunosuppression.

Cell mediated immunity (CMI) was assessed by the ImmuKnow assay in 12 patients after kidney transplantation, who presented with viral infection. Treatment included lowering of immunosuppression in all cases and antiviral treatment if indicated. The assay was repeated during the follow up. The ImmuKnow assay at time of presentation of viral infections was 56.8+/-58.2 (range 3-178; median 22) ATP ng/ml. With the clearance of viral infection and lowering of immunosuppression, the assay showed an increase in the level of CMI at 194.5+/-118.9 (range 53-409; median 150) ATP ng/ml. There was viral clearance or stabilization in all cases and there was no incidence of allograft rejection. The ImmuKnow assay of CMI can be used to titrate initial immunosuppression reduction and its subsequent increase, in patients with viral infection after transplantation.

Adenosine Triphosphate↗
PubMed2005

Aging and sympathetic modulation of immune function in Fischer 344 rats: effects of chemical sympathectomy on primary antibody response.

In aged Fischer 344 (F334) rats, sympathetic innervation of the spleen is markedly diminished compared with young rats. To determine if this diminished noradrenergic (NA) innervation maintains a functional connection with the immune system, 3- and 17-month-old male F344 rats were treated with the NA-selective neurotoxin, 6-hydroxydopamine (6-OHDA), to ablate peripheral NA nerve fibers. In sympathectomized rats immunized with keyhole limpet hemocyanin (KLH), a T-dependent protein antigen, anti-KLH IgM, IgG, IgG1, IgG2b antibody titers were increased in young and old rats 14 days after immunization compared to vehicle controls. Furthermore, the number of IgM and IgG anti-KLH antibody-secreting spleen cells was elevated 7 and 14 days post-immunization. These effects were prevented by pretreatment with desipramine, a catecholamine uptake blocker that blocks 6-OHDA uptake and subsequent sympathectomy. Chemical sympathectomy also increased KLH-induced proliferation in vitro by spleen cells from old, but not young animals. Isoproterenol (ISO), a beta-adrenergic receptor agonist, elicited a rise in cAMP in spleen cells from NA-intact young and old rats, but the increase was attenuated in spleen cells from old rats. These results demonstrate that, although NA innervation in the F344 rat spleen is diminished with age, sympathetic signaling of the immune system remains intact. Thus, the SNS can inhibit antibody produced in response to a protein antigen in both young and old F344 rats.

Adrenergic beta-Agonists↗
PubMed1994

The role of dietary sources of nucleotides in immune function: a review.

Dietary sources of preformed purines and pyrimidines seem to be important for optimal function of the cellular immune response. It was previously assumed that nucleotides were not needed for normal growth and development, but the results described in this review demonstrate a need for nucleotides in the response to immunological challenges. This effect is likely due to a requirement for preformed pyrimidines for proper development and activation of T cells. The need for sources of preformed nucleotides in defined formulas such as parenteral and enteral formulas and infant formulas is suggested by the studies reviewed below.

Animals↗
PubMed1977

[Possible disorder of tissue immunity function in mothers who have given birth to a child with Down's disease].

The rates of DNA synthesis were studied in PHA-stimulated lymphocytes from the peripheral blood of mothers giving birth to a child with Down's disease. For control purposes a group of donors of the same age and sex were studied as wells. A decrease of 3H-thymidine incorporation was detected in the lymphocytes of the mothers of such children. The found differences were due to a drop of lymphocyte PH-reactivity in the older maternal age group (over 30 years). Interrelation between the changed function of the maternal immune system and the birth of children with chromosome unbalance are discussed.

Adult↗
PubMed1985

Immune function, autoimmunity, and selective immunoprophylaxis in the aged.

Many changes occur in the immune system with age. The involution of the thymus plays a major role in immune senescence. Related to this event are the altered ratio of helper to suppressor T-lymphocyte subsets, decrease in immune response by both cell-mediated and humoral branches of the immune system, and increase in autoimmune activity. The clinical implications of these changes are the elderly person's increased susceptibility to infections such as pneumococcal pneumonia, influenza A, and tetanus as well as increased autoimmune activity, reflected by pernicious anemia. Other changes may be increased susceptibility to neoplasms and perhaps acceleration of the aging process. A high index of suspicion should be present for the diagnosis of pernicious anemia in the elderly population. Knowledge of the many autoantibodies that might be present without illness is important when evaluating for disease processes. The relationship of the senescent immune system to the aging process is still unknown. Investigations of this matter, as well as of the function of immune system components and their relationship to disease processes, are continuing. Most methods proposed for enhancing the immune system are still experimental. However, immunizations have been proved to be an effective means of reducing morbidity and mortality from certain infectious diseases in the elderly. Therefore, it is strongly recommended that all elderly persons who are at risk for pneumococcal pneumonia, influenza, and tetanus receive the proper immunizations.

Aged↗
PubMed2004

Immune functions in mice lacking Clnk, an SLP-76-related adaptor expressed in a subset of immune cells.

The SLP-76 family of immune cell-specific adaptors is composed of three distinct members named SLP-76, Blnk, and Clnk. They have been implicated in the signaling pathways coupled to immunoreceptors such as the antigen receptors and Fc receptors. Previous studies using gene-targeted mice and deficient cell lines showed that SLP-76 plays a central role in T-cell development and activation. Moreover, it is essential for normal mast cell and platelet activation. In contrast, Blnk is necessary for B-cell development and activation. While the precise function of Clnk is not known, it was reported that Clnk is selectively expressed in mast cells, natural killer (NK) cells, and previously activated T-cells. Moreover, ectopic expression of Clnk was shown to rescue T-cell receptor-mediated signal transduction in an SLP-76-deficient T-cell line, suggesting that, like its relatives, Clnk is involved in the positive regulation of immunoreceptor signaling. Stimulatory effects of Clnk on immunoreceptor signaling were also reported to occur in transfected B-cell and basophil leukemia cell lines. Herein, we attempted to address the physiological role of Clnk in immune cells by the generation of Clnk-deficient mice. The results of our studies demonstrated that Clnk is dispensable for normal differentiation and function of T cells, mast cells, and NK cells. Hence, unlike its relatives, Clnk is not essential for normal immune functions.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Evaluation of immune functions of rainbow trout (Oncorhynchus mykiss)--how can environmental influences be detected?

In fish, the first line of defense against infectious microorganisms is based on a broad range of nonspecific humoral and cellular immune mechanisms ("innate immunity") which without prior specific activation can act in forming a more static barrier (Fish Shellfish Immunol. 10 (2000) 243; Dev. Comp. Immunol. 25 (2001) 827). This natural resistance is normally effective enough to protect fish from infectious diseases until specific immune responses are being induced (Fig. 1; Dev. Comp. Immunol. 25 (2001) 841). Healthy fish exhibit both nonspecific and specific immune responses depending directly on environmental temperature. Pollution of the natural aquatic environment with industrial or agricultural sewage is an important immunosuppressing factor resulting in higher susceptibility to infectious diseases. To date, the possible immunotoxicity of a substance is evaluated using quantification of humoral factors like lysozyme, complement, C-reactive protein or total immunoglobulins but less often using functional assays. Furthermore, most of the functional assays (phagocytosis, respiratory burst, proliferative response) are based on the measurement of the response of resting but not of specific activated immune cells. However, the physiological responses of the immune system to an infection are based on a complex, stepwise activation and proliferation, especially of the specific immune functions after first contact to the microorganisms. In this report we describe in vitro methods for the evaluation of cellular immune functions of different leukocyte populations after specific in vivo triggering of the immune system. Parameters to be evaluated are activation and proliferation of leukocyte populations, phagocytosis and respiratory burst, secretion of antigen-specific antibodies and specific cell-mediated cytotoxicity. Furthermore, challenge models with bacterial (Aeromonas salmonicida) and viral pathogens (Viral Haemorrhagic Septicemia Virus, VHSV) are presented.

Animals↗
PubMed2000

Immune function.

The innate and the adaptive immune systems have evolved to provide a rapid and specific means for protecting hosts against the many microbes experienced over a lifetime. These two immune responses interact cooperatively to enhance the host defense. Defects in either of these two pathways can have devastating consequences, as evidenced [figure: see text] by primary immune deficiencies, many of which are discussed in this issue of the Pediatric Clinics of North America. The immune system has a central role in the pathogenesis of many disorders that involve an inflammatory response, including allergic and autoimmune diseases. New and more effective therapies for these many disorders will develop as the understanding of the immune system and its many secreted mediators continues to increase.

B-Lymphocytes↗