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Effect of breed (Angus vs Simmental) on immune function and response to a disease challenge in stressed steers and preweaned calves.

Two experiments were conducted with feeder steer calves and preweaned calves to determine the effects of breed on immune response. In Exp. 1, newly weaned Angus (n = 24) and Simmental (n = 24) steer calves were blocked by weight within breed and randomly assigned to 12 pens with four calves per pen. The basal diet consisted of 87% corn silage (DM basis) and 13% of a soybean meal-mineral-vitamin supplement. Steers were allowed ad libitum access to feed throughout the study. On d 2 following weaning, calves received an intranasal inoculation of infectious bovine rhinotraecheitis virus (IBRV; 2.7 x 10(8) CCID50). Rectal temperatures in response to the IBRV were higher (P < .05) in Angus calves. On d 9, calves were injected i.m. with 10 mL of a 25% pig red blood cell (PRBC) suspension. Total immunoglobulin (Ig) and IgM titers against PRBC were higher (P < .05) for the Angus calves. Breed did affect cell-mediated immune response to phytohemagglutinin (PHA). In Exp. 2, preweaned (16 Angus and 16 Simmental) calves were selected based on breed, body weight, and sex. On 0 d, all selected calves were injected i.m. with 10 mL of a 25% PRBC suspension. Total Ig and IgG titers against PRBC were higher (P < .05) for Angus calves. On d 28, lymphocytes were isolated from peripheral blood obtained from eight calves per breed. Peripheral lymphocytes from the Angus calves had a greater (P < .07) blastogenic response to 6.25 microg/mL of PHA than lymphocytes from Simmental calves. Results indicate that the immune response of Angus and Simmental calves may differ.

Animals↗

Nucleic acids and/or their components: a possible role in immune function.

Dietary sources of nucleic acids and/or their components, have not been considered essential for normal growth and development. However, growing evidence shows that the compounds regulate various steps of the immune system and demonstrate the necessity of the compounds in the response to immunological challenge. The significance of exogenously administered purine or pyrimidine bases, nucleotides, and nucleosides in the immune response is reviewed.

Humans↗

Normal immune function of monocyte-derived dendritic cells from HIV-infected individuals: implications for immunotherapy.

Dendritic cells (DC) are the most potent cells involved in the generation of primary and secondary immune responses. To assess the feasibility of using autologous DC as immunotherapy for HIV disease, we analyzed a variety of immune parameters using DC isolated from HIV-infected (HIV+) individuals, as well as DC obtained from HIV-uninfected (HIV-) individuals infected in vitro with HIV. After stimulation with recombinant CD40 ligand (CD40LT), cytokine and beta-chemokine production were similar by DC from HIV- donors infected in vitro with the CCR5-using HIV Ba-L strain (n = 8) compared with uninfected DC from the same donors. Production of beta-chemokines, but not of cytokines, was increased by a CXCR4-using IIIB strain-infected DC (n = 7). Stimulation of HIV-infected DC with CD40LT decreased infection in Ba-L-infected DC, but had no effect on IIIB-infected DC. Consistent with this finding, CD40LT down-regulated CCR5 and up-regulated CXCR4 expression on DC. Monocyte-derived DC were also propagated from 15 HIV+ and 13 HIV- donors. They exhibited similar expression of costimulatory molecules and produced similar amounts of IL-12, IL-10, and beta-chemokines, following stimulation. By contrast, stimulated PBMC from HIV+ patients exhibited decreased IL-12 and increased IL-10 production. In summary, phenotype, cytokine secretion, and beta-chemokine production by DC from HIV+ individuals were normal. These cells may prove useful in boosting cellular immune responses in HIV+ individuals.

Adoptive Transfer↗

Effects of PCB congeners on the immune function of Mytilus hemocytes: alterations of tyrosine kinase-mediated cell signaling.

Polychlorinated biphenyls (PCBs) are industrial chemicals which have been released into the environment resulting in widespread and persistent contamination. PCBs exist as 209 different congeners depending on the chlorine substitution on the biphenyl rings; the physical properties and the toxic effects of a PCB congener are structure-dependent. In this work, individual ortho-substituted non coplanar PCB congeners were tested for their effects on the function of mussel (Mytilus galloprovincialis Lam.) hemocytes. Moreover, the possibility that in mussel hemocytes different PCBs may affect the signal transduction pathways involved in the immune response was investigated, with particular regards to relevant components of tyrosine-kinase mediated cell signaling. The results were compared with those obtained with a model of non-ortho-substituted coplanar congener. The results demonstrate that the di-ortho-substituted, non coplanar PCB congeners P47 (2,2',4,4'-tetrachlorobiphenyl) and P153 (2,2',4,4',5,5'-hexachlorobiphenyl) can alter immune parameters of mussel hemocytes, such as microbicidal activity and lysosomal enzyme release, respectively. Both congeners, as well as the non-ortho, coplanar congener P77 (3,3',4,4'-tetrachlorobiphenyl) significantly reduced hemocyte lysosomal membrane stability; however, P77 had no effect on either bacterial killing or lysozyme release. P47, P153 and P77 affected different components of tyrosine kinase-mediated cell signalling; in particular, they lead to a time-dependent increase in the phosphorylation level of the stress activated p38 and JNK Mitogen Activated Protein Kinases (MAPKs), as evaluated by Western blotting of hemocyte protein extracts with specific anti-phospho-MAPK antibodies. P153 also increased the level of phosphorylated ERK (extracellularly regulated) MAPKs. Moreover, non coplanar P47 and P153 caused increased tyrosine phosphorylation of the transcription factor STAT5, thus possibly affecting gene expression, whereas coplanar P77 was ineffective. The results demonstrate that MAPKs, and in particular the stress-activated p38 and JNK MAPKs, that represents a key step in the response of mussel hemocytes to bacterial infection, are a target for different non coplanar and coplanar PCB congeners. The results also show functional differences between different PCB congeners with respect to the hemocyte functions. However, chlorine substitution at the ortho positions is not necessarily related to immunotoxicity: the hexachlorinated P128 (2,2',3,3',4,4'-hexachlorobiphenyl) had no significant effect on mussel hemocytes, whereas its isomer P153, that represents a major component of environmental PCBs, and that is accumulated in mussel tissues, significantly affected both aspects of the immune response and relevant signal transduction pathways. These are the first data on the effects and possible mechanisms of immunotoxicity of non coplanar PCBs in mussel hemocytes. The results support the hypothesis that the innate immune system is a sensitive target for these contaminants in both vertebrates and invertebrates. Moreover, when considering that non coplanar congeners are present both in commercial mixtures and, in higher proportions, in environmental samples, the results suggest that bivalve hemocytes represent a useful model for evaluating the potential immunotoxicity of PCB contamination.

Animals↗

Protein A induced abrogation of cyclophosphamide toxicity is associated with concomitant potentiation of immune function of host.

This report confirms our previous observation that protein A (PA) of Staphylococcus aureus Cowan I reduces the cyclophosphamide (Cy) induced toxicity. PA treated animals recover quickly from the toxic effects of Cy. We have exhaustively studied the role of specific and nonspecific immunity in the protection of the animals. It was observed that PA helped the animals in the accelerated regeneration of leukocytes of blood (p less than 0.001) and different lymphoid organs like thymus (p less than 0.001), spleen (p less than 0.01) and bone marrow (p less than 0.01). Increased number and function of macrophages was also observed in PA (p less than 0.001) and PA+Cy (p less than 0.001) groups. PA, on one hand enhanced the cell mediated immunity while suppressed the humoral immunity as was assessed by increase in delayed type hypersensitivity response (p less than 0.001) and decreased in plaque forming cells (p less than 0.001), EAC-rosettes (p less than 0.001), hemagglutination (p less than 0.001) and hemolysin titre (p less than 0.05). On the basis of above observations we propose that the immunomodulatory activity of PA helped the animals to remain alive in two ways- (1) by early generation of the cells depleted by the Cy thus helping animals to repair the damaged immune system and fast clearance of the toxic metabolites of Cy (2) by temporarily suppressing the cells responsible for humoral immunity which are more susceptible to Cy metabolites.

Adjuvants, Immunologic↗

The effect of a high partial pressure of carbon dioxide environment on metabolism and immune functions of human peritoneal cells-relevance to carbon dioxide pneumoperitoneum.

OBJECTIVE: Our purpose was to evaluate in vitro the effect of a high partial pressure of carbon dioxide environment used in laparoscopy on metabolic and immune response of various human peritoneal cells. STUDY DESIGN: Polymorphonuclear leukocytes were obtained from 5 healthy volunteers, peritoneal macrophages were obtained from the effluent of 8 patients undergoing continuous ambulatory peritoneal dialysis, and human peritoneal mesothelial cell cultures were prepared from omentum derived from 5 patients undergoing elective surgery. The cells were exposed to a laparoscopy-like environment (1 atmosphere carbon dioxide and 0.2 atmosphere oxygen), to a control gas mixture (1 atmosphere helium and 0.2 atmosphere oxygen), or air for 3 hours. After exposure to gas mixtures, cell functions were tested at various recovery periods. RESULTS: Three hours of exposure to a high partial pressure of carbon dioxide had no effect on viability of peritoneal macrophages and human peritoneal mesothelial cells, tested by trypan blue dye uptake and lactate dehydrogenase release. A high partial pressure of carbon dioxide decreased the mitochondrial dehydrogenases activity of peritoneal macrophages and human peritoneal macrophage cells by 60%, assayed by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction. High partial pressure of carbon dioxide blocked the superoxide release from activated polymorphonuclear leukocytes and the secretion of interleukin 1beta from stimulated peritoneal macrophages, and human peritoneal macrophage cells were decreased by 15% and 30% and the secretion of tumor necrosis factor-alpha from peritoneal macrophages was suppressed by 85%. Mitochondrial activity, polymorphonuclear leukocyte function, and interleukin 1beta and tumor necrosis factor-alpha secretion returned to normal after a recovery period of 12 to 24 hours, 4.5 hours, and 24 hours, respectively. In the control experiments exposure of cells to helium had no suppressive effect. CONCLUSIONS: Exposure of cells to a high partial pressure of carbon dioxide environment suppresses the inflammatory and metabolic responses of peritoneal cells. We suggest that this suppressive effect may contribute to the low postsurgery adhesion formation and the reduction in postoperative pain observed in laparoscopy. Nevertheless, the suppression of the immune response should also be taken into account for operations involving a high risk of bacterial dissemination.

Ascitic Fluid↗

Effects of 4-[4''-(2'',2'',6'',6''-tetramethyl-1''-piperidinyloxy)amino]-4'-de methylepipodophyllotoxin on immune function in mice.

4-[4''-(2'',2'',6'',6''-Tetramethyl-1''-piperidinyloxy)amino]-4'- demethylepipodophyllotoxin (GP-7) 10-40 mg.kg-1 ip daily for 7 d reduced the specific antibody formation of splenocytes, serum agglutinin titer, and hemolysin HC50 in mice immunized with SRBC. GP-7 inhibited the footpad delayed hypersensitivity reaction and decreased the weights of spleen and thymus, but did not affect the phagocytic function of the peritoneal macrophages. In vitro the proliferation of mouse splenic lymphocytes activated by Con A was markedly inhibited by GP-7 in a concentration- dependent manner. At concentrations of 0.05-5 mg.L-1, the inhibition rates were 24-96%. These results suggested that GP-7 was an immunosuppressive agent.

Agglutinins↗

The effects of injectable sodium selenite on immune function and milk production in Sardinian sheep receiving adequate dietary selenium.

The aim of this preliminary study was to determine the effects of selenium (Se) injection on Se status, cell-mediated immunity (CMI), milk yield and milk somatic cell count (MSCC) of ewes fed adequate amounts of Se, and on Se status, passive immunization and CMI of their offspring. Thirty days before lambing, 36 Sardinian ewes were assigned to one of three groups. One group (NT) was not treated; a second group (BL) was given 5 mg of Se on day 30 before lambing; a third group (BLL) was given 2.5 mg of Se on day 30 before lambing and at lambing. Selenium was given intramuscularly as sodium selenite. Selenium status was assessed by measuring glutathione peroxidase activity of erythrocytes (GSHpx-E). The CMI was measured by determining the increases in double skinfold thickness after intradermal injection of phytohaemagglutinin (PHA). Compared to their NT counterparts, ewes belonging to BL and BLL groups and their offspring had significantly higher GSHpx-E (P < 0.01). The GSHpx-E values of lambs were positively related to those of their mothers (P < 0.0005). Ewes of group BL had a greater (P < 0.01) response to PHA 6 h after injection than ewes of the NT group. Lambs born to BL and BLL ewes had a greater (P < 0.0001) response to PHA 24 h after injection. Responses of ewes and lambs to PHA 24 h after injection were positively related (P < 0.05). Serum immunoglobulin at 10 days of age did not differ significantly among the three groups of lambs. Compared to the NT group, milk yield on day 70 of lactation was significantly higher in BL ewes (P < 0.05). The MSCC was not affected significantly by Se injection. Immunoresponsiveness and milk yield might represent additional and appropriate criteria to consider when re-evaluating Se requirements of dairy sheep.

Animals↗

Influence of the H-2u haplotype on immune function in F1 hybrid mice. I. Antigen presentation.

Previously, we reported that myelin basic protein (MBP) peptide 1-37 contains an encephalitogenic epitope for PL/J mice, and MBP peptide 89-169 is encephalitogenic for SJL/J mice. (SJPL)F1 hybrid mice do not respond to immunization with these peptides in a co-dominant manner because the encephalitogenic response to peptide 1-37 dominates. To examine this phenomenon more closely, we tested the ability of MBP-primed parental or F1 T cells to respond to MBP or MBP peptides in the context of PL, SJL, or F1 antigen-presenting cells (APC). It was found that the F1 T cells responded to either the protein or the peptides when these were presented in the context of F1 or PL APC. However, F1 T cells would not respond to MBP in the context of SJL APC, although the latter cells were functionally intact. This effect was not antigen-specific because SJL APC would not present ovalbumin or PPD to primed F1 T cells. F1 T cells from mice immune to the strongly antigenic bacterium Listeria monocytogenes responded to bacterial antigens presented by SJL APC, although at a significantly lower level compared to the results obtained when these antigens were presented by F1 or PL APC. This finding implied that unbalanced antigen presentation was a quantitative rather than a qualitative phenomenon. When F1 hybrid mice from other strain combinations were tested, a similar effect was observed whenever one of the parental strains was PL/J. This effect was mapped to the MHC in MHC-congenic B10 mice.

Animals↗

C-type lectins and galectins mediate innate and adaptive immune functions: their roles in the complement activation pathway.

In recent years, a 'new' pathway for complement activation mediated by the mannose-binding lectin (MBL) has been described as a key mechanism for the mammalian acute phase response to infection. This complement activation pathway is initiated by a non-self recognition step: the binding of a humoral C-type lectin [mannose-binding lectin (MBL)] to microbial surfaces bearing 'foreign' carbohydrate determinants. The recognition factor, MBL, is associated with a serine protease [MBL-associated serine protease (MASP)] which, upon MBL binding to the microbial ligand, activates the complement component C3, leading to either (a) phagocytosis of the opsonized target via the complement receptor, or (b) humoral cell killing via assembly of the membrane attack complex. Galectins (formerly known as S-type lectins) modulate activity of the complement receptor 3 (CR3), the macrophage membrane receptor for complement components C3b and iC3b, downstream products of the MBL pathway which are covalently bound to 'target cells. Galectins also mediate macrophage- and dendrocyte-adhesion to lymphocytes activated by signaling through another C-type lectin, the L-selectin, leading to immunoglobulin-mediated responses. Thus, the functional interplay of MBL, galectins and L-selectin in the acute phase response neutralizes the microbial challenge, and lead to further adaptive immunity. Although the observation of various components of the lectin pathway in different invertebrate species demonstrates the high conservation and ancient roots of the components of innate immunity, there has previously been no evidence supporting the possibility that the integral lectin-mediated complement activation pathway is present in invertebrates. We now have evidence for the coexistence of homologs of all the pathway's key components (MBL, MASP, C3, and galectin) in the protochordate Clavelina picta, suggesting the lectin-mediated pathway of complement activation preceded the immunoglobulin pathway in evolution. Therefore, despite being 'new' to the textbooks, experimental evidence indicates that this pathway is ancient, and has been conserved intact throughout its evolution.

Amino Acid Sequence↗

Modulation of immune function and weight loss by L-arginine in obstructive jaundice in the rat.

Jaundiced surgical patients have a high incidence of postoperative complications. Many causative factors have been identified including cachexia and immune suppression. The amino acid L-arginine has anabolic and immunostimulatory properties. It was hypothesized that dietary supplementation with L-arginine would diminish the weight loss and immune suppression of obstructive jaundice. Sixteen male Wistar rats rendered jaundiced by bile duct ligation were allocated to two groups. The test group (n = 8) received drinking water supplemented with 1.8 percent L-arginine ad libitum and the control group (n = 8) received a solution of isonitrogenous glycine. Both groups had free access to standard chow. Body-weight, and fluid and food intake were recorded. After 21 days, delayed-type hypersensitivity to 2,4-dinitrofluorobenzene was assessed. Animals receiving L-arginine consumed more food than controls (mean(s.e.m.) 414(16) versus 360(13) g, P < 0.05) and lost less weight (mean(s.e.m.) proportion of initial body-weight lost 7.8(1.2) versus 14.8(1.4) percent, P < 0.05). The delayed-type hypersensitivity response was significantly greater in rats receiving L-arginine (mean(s.e.m.) increase in ear thickness 23.9(2.7) versus 9.4(2.1) percent, P < 0.05). In this animal model of obstructive jaundice dietary supplementation with L-arginine diminished both weight loss and immune suppression.

Animals↗

Cytomegalovirus (CMV)-specific CD4+ T lymphocyte immune function in long-term survivors of AIDS-related CMV end-organ disease who are receiving potent antiretroviral therapy.

To better understand the relation of cytomegalovirus (CMV)-specific CD4+ T lymphocyte immunity and clinical outcome in AIDS-related CMV end-organ disease, 2 patient groups were prospectively studied: patients recently diagnosed with active CMV end-organ disease and survivors of CMV retinitis who had responded to highly active antiretroviral therapy and had quiescent retinitis when anti-CMV therapy was discontinued. Most patients with active CMV disease had negative CMV-specific CD4+ T lymphocyte responses at diagnosis, as measured by lymphoproliferation (7/7) or cytokine flow cytometry (3/5) assays. In contrast, all 10 subjects with quiescent retinitis and >150 absolute CD4+ T lymphocytes/microL whose anti-CMV therapy was discontinued during 6 months of follow-up had positive CMV-specific immune responses at least once by each assay. However, 6 of these 10 subjects also had negative CMV-specific immune responses > or =1 time. Such patients may be at risk for future CMV disease progression and should be closely monitored.

AIDS-Related Opportunistic Infections↗