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[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↗

Innate immune functions of plasmacytoid dendritic cells.

Plasmacytoid dendritic cells (pDCs) are specialized immune cells capable of producing large amounts of type I interferon (IFN) and other proinflammatory cytokines in response to viral infections. To date, a multicomponent cytoplasmic transductional-transcriptional complex and a spatiotemporal mechanism have been revealed in pDCs that mediate the rapid and robust IFN production after Toll-like receptor activation. Multiple regulatory mechanisms involving surface receptors, intracellular and exogenous factors as well as virally encoded molecules have been shown to modulate the IFN responses in these cells. The unique innate immune functions of pDCs are crucial both in infectious diseases and in autoimmune diseases. The recent research progress provides an in-depth understanding of the biology of pDCs and a sensible basis for future therapeutic interventions.

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↗

Organochlorine concentrations, reproductive physiology, and immune function in unique populations of freshwater Atlantic stingrays (Dasyatis sabina) from Florida's St. Johns River.

Within the past decade, reproductive and health disorders have been reported to occur in unique populations of Atlantic stingrays (Dasyatis sabina) inhabiting certain components of Florida's St. Johns River. Since these irregularities are consistent with the alleged effects of organochlorine (OC) contaminant exposure in other Florida wildlife, the goal of this study was to examine possible associations between OC concentrations and reproduction and/or immune function in stingrays from this river system. Liver concentrations of 30 OC pesticides/pesticide metabolites and total polychlorinated biphenyls (PCBs) were measured and compared in D. sabina collected from four central Florida lakes of the St. Johns River: Lake George, Lake Harney, Lake Jesup, and Lake Monroe. Reproductive biology, serum testosterone and 17beta-estradiol concentrations, and circulating white blood cell counts were examined and compared in stingrays from lakes that were determined to contain low (Lake George), intermediate (Lake Monroe), and high (Lake Jesup) levels of pesticide contamination, based on the results of liver OC assessments. Successful breeding occurred in Lake Jesup stingrays, indicating that the degree of OC accumulation in these animals is not high enough to cause reproductive impairment. However, elevated serum steroid concentrations and white blood cell counts were observed in Lake Jesup stingrays, suggesting that endocrine and immune function may be altered in these animals due to OC exposure and/or other, as yet unknown, ecological factors. Inconsistencies in the reproductive success of Lake Monroe stingrays were observed, confirming earlier reports of reproductive complications in this sub-population. Based on these findings, previous occurrences of reproductive failure in St. Johns River stingrays may be due to environmental factors other than OC exposure.

Animals↗

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↗

A direct mechanistic link between growth control and a tumor cell immune function: increased interleukin-8 secretion accounts for elimination of Oct-1 antisense transformants from scid mice.

BACKGROUND: Tumorigenesis involves the aberrant function of proteins that regulate growth control, including Oct-1. Oct-1 is a DNA binding transcription factor that activates genes that encode proteins required for S-phase and cell growth. For example, Oct-1 activates the histone H2B promoter and the promoters for the snRNPs. Oct-1 also represses certain promoters, including promoters of immune function genes, such as the IL-8 and the HLA-DRA genes. MATERIALS, METHODS AND RESULTS: Oct-1 antisense transformants were determined to have reduced growth rates and other characteristics of growth control. Also, Oct-1 antisense transformants endured for a shorter time in scid mice, being attributable to the increased expression of IL-8 by the Oct-1 antisense transformants. CONCLUSION: These results may help resolve the conundrum of why growth control de-regulation alone is not enough for tumorigenicity. The results also support the conclusion that the molecular mechanisms of growth control de-regulation and tumor cell immune functions are directly linked.

Animals↗

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↗

[The effects of jianpizengmian granule on tumor growth and immune function].

The effects of Jianpizengmian (JPZM) granule on tumor growth and immune function were researched in tumor-bearing mice. The results showed it had significant inhibiting activity against S180 and HePA by oral JPZM. The inhibitory rate of JPZM reached 46.25% and 45.57%. JPZM could markedly increase the index of spleen and thymus, the level of serum hemolysin and the spleen lymphocytes transformation in tumor-bearing mice, compared to control group (H2O) respectively.

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↗

DNase II deficiency impairs innate immune function in Drosophila.

DNase II enzymes are highly conserved proteins that are required for the degradation of DNA within phagolysosomes. Engulfment of apoptotic cells and/or bacteria by phagocytic cells requires the function of DNase II to completely destroy ingested DNA. Mutation of the dnase II gene results in an increase of undegraded apoptotic DNA within phagocytic cells in mice and nematodes. Additionally, reduction of DNase II enzymatic activity in Drosophila melanogaster has been shown to lead to increased accumulation of DNA in the ovaries. Due to the importance of DNA clearance during infection, we hypothesized that a severe reduction of DNase II activity would result in diminished immune function and viability. To test this hypothesis, we knocked down DNase II activity in flies using RNAi. As expected, expression of a dnase II-RNAi construct in flies resulted in a dramatic reduction of DNase II activity and a significant decrease in total hemocyte numbers. Furthermore, infection of dnase II-RNAi flies with Gram negative or positive bacteria resulted in a severe reduction in fly viability. These results confirm that DNase II and the ability to clear macromolecular DNA is essential for maintaining proper immune function in Drosophila.

Animals↗