bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of four neuropeptides on the degranulation of mucosal mast cells from sheep
Authors: STEWART MELINDA J , EMERY DAVID L , McCLURE SUSAN J , BENDIXSEN TUAN 
Published: June 2007

SummaryIsolated mucosal mast cells (MMC) were used to examine the ability of four neuropeptides. substance P, vasoactive intestinal peptide. β‐endorphin and somatostatin, to release mediators in the presence or absence of parasite antigen. None of the neuropeptides induced the release of sheep mast cell protease (SMCP) or histamine from MMC of helminth‐immune sheep in the absence of parasite antigen. Incubation of immune MMC with 100 and 1.0μg/mL parasite antigen induced 32.1 and 15.5% specific SMCP release, respectively. While the neuropeptides did not augment SMCP release at 100 μg/mL parasite antigen, significant enhancement (40‐98%) of SMCP release at 1 μg/mL antigen was obtained by each neuropeptide at concentrations from 10−8 to 10−12 mol/L. The results provide additional support for modulation of MMC degranulation by neural activity in sheep and, to our knowledge, this is the first demonstration that the threshold antigen concentration for allergic responses may also be lowered by neuropeptides to render the reaction more sensitive to antigen.
Anti‐receptor antibodies inhibit Pseudomonas aeruginosa binding to the cornea and prevent corneal perforation
Authors: HOBDEN JEFFERY A , GUPTA SURESH K , MASINICK SHARON A , WU XUAN , KERNACKI KAREN A , BERK RICHARD S , HAZLETT LINDA D 
Published: June 2007

SummaryA polyclonal antibody (pAb) against gangliotetraosylceramide (asialo GM1), a glycolipid to which bacterial pili and LPS bind, and a mAb against a 66 kDa pilus‐binding protein purified from adult mouse corneal epithelium were used to determine if antibodies against host receptors for bacterial adhesins could inhibit bacterial binding to wounded corneal epithelium and protect ocularly challenged mice from corneal perforation when topically applied. Bacteria were mixed with anti‐66 kDa mAb, a mixture of anti asialo GM1 pAb and anti‐66 kDa mAb, an irrelevant control mAb (anti‐human histocompatibility Ag HLA‐DR5) or PBS prior to application to scarified corneas in organ culture. The combination of the two antibodies or the anti‐66 kDa mAb alone was effective in reducing bacterial adherence compared with either PBS or the antibody control. To determine if these antibodies were protective in vivo, corneas of C57BL/6J mice were scarified and inoculated with Pseudomonas aeruginosa. Eyes were treated topically with anti‐asialo GM1 pAb, anti‐66 kDa mAb, a mixture of the two or control mouse serum. More serum‐treated corneas perforated compared to corneas from any other group (p≤= 0.005) by 30 days post infection. Treatment with a combination of the two antibodies resulted in significantly less corneal pathology 30 days p.i. when compared to any other treatment (p≤= 0.005). These data provide evidence that antibodies against host corneal receptors significantly inhibit bacterial binding in vitro and when applied topically in vivo, lessen the severity of ocular disease characteristic of P. aeruginosa keratitis.
Distribution of antigen specific memory T cells in lymph nodes after immunization at peripheral or mucosal sites
Authors: PREMIER ROBERT R , JACOBS HELEN J , BRANDON MALCOLM R , MEEUSEN ELS NT 
Published: June 2007

SummaryThe distribution of antigen‐specific memory T cells in different lymph nodes of sheep was determined using an antigen‐specific in vitro proliferation assay. Lymph nodes were collected from sheep immunized simultaneously with avidin or ovalbumin in a peripheral tissue site (hind leg muscle) and keyhole limpet haemocyanin (KLH) in an intestinal tissue site (gut wall or colonic mucosa). The results showed a consistently high proliferative response in typical peripheral lymph nodes (popliteal and prescapular) and a low or negative response in gastrointestinal lymph nodes (abomasal and jejunal) while the response in other nodes was variable. The low proliferative response in the gastrointestinal lymph nodes was not due to the presence of supressor CD8+ lymphocytes and the proliferative response could not be raised to peripheral lymph nodes levels with the addition to cultures of IL‐2 or mitomycin‐C treated peripheral lymph node cells. The high proliferative response in the peripheral lymph nodes was not suppressed by the addition of mitomycin‐C‐treated gastric lymph node cells but was dramatically reduced by the addition of mAb against the IL‐2‐receptor or by depletion of CD4+ T cells. The results suggest that antigen‐specific proliferative memory T cells, which may be Th1‐like memory cells, preferentially migrate to peripheral lymph nodes independent of their site of induction.
Dissociation of production of interleukin‐4 and interleukin‐5
Authors: SEWELL WILLIAM A , MU HONG‐HUA 
Published: June 2007

SummaryInterleukin‐4 (IL‐4) and IL‐5 are cytokines with important roles in IgE production and eosinophilia. Interleukin‐4 is essential for IgE production, and IL‐5 is the major factor involved in the production and activation of eosinophils. These two phenomena commonly occur together in parasitic infestation and allergic disease. Both cytokines are produced by T helper 2 (Th2) and Th0 cells but not by Th1 cells, and in a number of experimental systems IL‐4 is required for the production of IL‐5. This article presents evidence that IL‐4 and IL‐5 are not always co‐ordinately produced. There is evidence for selective production of either IL‐4 or IL‐5 in response to immune stimulation by different adjuvants. Dissociation of production of these two cytokines has also been reported in several pathological situations. An example is intrinsic or non‐atopic asthma, with eosinophilic bronchitis but without elevated IgE production, where there is evidence for excessive production of IL‐5 but not IL‐4. Different microenvironmental factors may favour production of either IL‐4 or IL‐5. For example, IL‐2 stimulates the production of IL‐5 but not IL‐4. Therefore the Th2 model does not account for all immune responses involving IL‐4 or IL‐5. Responses characterized by IL‐4 without IL‐5, and IL‐5 without IL‐4, can also occur.
Signal minus 1: A key factor in immunological tolerance to tissue‐specific self antigens?
Authors: PARISH CHRISTOPHER R 
Published: June 2007

SummaryRecent data suggest that many autoreactive T cells, particularly to tissue‐specific self antigens, can escape thymic deletion. The current dogma is that these autoreactive T cells are silenced by the failure of most tissues to provide co‐stimulation (signal 2), antigen alone (signal 1) inducing T cell unresponsiveness. However, I propose that activation of autoreactive T cells frequently occurs but autodestruction by effector T cells is tightly regulated. This phenomenon is most evident with lymph node metastasizing tumour cells where the regional lymph node can mount a vigorous response to the invading tumour cells but tumour growth is unimpaired. I suggest that autodestruction is prevented by inhibitory receptors on T cells which recognize class I MHC structures on target cells. These receptors, which I propose deliver 'signal minus T to T cells, were recently described on NK cells and a subpopulation of peripheral T cells. They are also strikingly similar to a family of anti‐self receptors that my laboratory described on murine T and B cells 15 years ago. In the ‘signal minus 1’model, antigen‐activated T cells acquire the inhibitory receptors when they become co‐stimulation independent and gain the ability to exit lymphoid organs and enter non‐lymphoid tissues. Thus, if autoreactive effector T cells encounter autoantigen in tissues they are functionally silenced by inhibitory receptor engagement and signal minus 1 delivery. In contrast, I propose that in response to intracellular infections, cells down‐regulate expression of their ligands for inhibitory receptors. Such a model allows infected cells to be selectively eliminated by effector T cells. If correct, the model predicts that effector T cells, whether foreign antigen‐ or autoantigen‐specific, can selectively respond to infected cells. This apparent‘usefulness’of autoreactive T cells may explain their observed persistence even after an encounter with autoantigen. It is also suggested that signal minus 1 may silence autoreactive B cells specific for tissue‐specific cell surface antigens and lack of signal minus 1 may partially explain the vigorous T cell response to allogeneic MHC. Finally, it is hypothesized that, in evolutionary’terms, inhibition of autodestruction by the recognition of a 'self marker’and delivery of signal minus 1 is an ancient process which probably emerged in early metazoans.
Antigen‐specific IgA‐secreting cells induced by peripheral vaccination
Authors: ROTHEL JS , CORNER LA , SEOW H‐F , WOOD PR , LIGHTOWLERS MW 
Published: June 2007

SummaryAntigen‐specific IgA‐secreting cells were shown to be generated in peripheral lymph nodes following s.c. vaccination. The efferent duct of prefemoral lymph nodes of sheep were cannulated prior to vaccination at a site draining to the cannulated node. Vaccines were contained a recombinant protein (Taenia ovis45W‐GST) and either incomplete Freund's, Quil A or A1(OH)3 as adjuvant. Lymph fluid was examined for the presence of 45W‐GST‐specific antibody by ELISA and antibody‐secreting cells by enzyme‐linked immuno‐spot (ELISPOT) assay. Large numbers of anti‐45W‐GST IgA‐secreting cells were detected at various times after vaccination as were IgM, IgG1, and IgG2‐secreting cells. For sheep vaccinated using incomplete Freund's adjuvant, up to 11% (> 1 million/day) of 45W‐GST‐specific ELISPOT were IgA‐secreting cells.
Malaria vaccine trials: The missing qualitative data
Authors: FERREIRA MU 
Published: June 2007

SummaryRecent population‐based efficacy trials of the synthetic malaria vaccine SPf66 have shown restricted, if any, clinical protection against Plasmodium falciparum infection. Despite the well‐established role of antibodies in effector responses against asexual blood‐stage malaria parasites, the titres of anti‐SPf66 IgG antibodies do not correlate with the ability of sera from vaccine recipients to inhibit parasite growth in vitro nor with partial clinical protection which could be detected in some trials. Qualitative or functional parameters of SP66‐induced antibody responses, such as IgG subclass composition and affinity, may be more predictive of clinical protection against malaria than quantitative estimates of antibody concentration or titre. Since these parameters are readily estimated by laboratory techniques currently available, and may be modulated by changes in vaccination protocols and by the use of different adjuvants, a better understanding of qualitative antibody responses induced by SPf66 and other asexual blood‐stage malaria vaccine candidates, and of their relationship with clinical protection in vivo, is urgently needed for the improvement of currently used immunization schedules.
Quantifying phagocytosis of Mycobacterium avium complex by human monocytes in whole blood
Authors: HEWISH MJ , MEIKLE AM , HUNTER SD , CROWE SM 
Published: June 2007

SummaryStudies of phagocytic efficiency in cells of the macrophage lineage have assumed additional importance since the discovery that HIV infection of these cells impairs their immune function. A rapid method has been developed for measuring phagocytosis of the opportunistic pathogen Mycobacterium avium complex by human monocytes. Fluoresceinated M. avium complex (F‐MAC) was incubated with whole blood at 37°C and the fluorescence of extra‐cellular F‐MAC was quenched using a vital blue stain. Monocytes were then stained with a monoclonal antibody (mAb) to human CD14 conjugated to phycoerythrin (PE) red cells were lysed, and the percentage of monocytes which had phagocytosed F‐MAC was measured by flow‐cytometry. The results were reproducible in samples of blood taken from individual donors over a period of 1or 2 weeks, and optimum F‐MAC concentrations and an optimum incubation time were determined by experiment. This method has the advantages of requiring only a small volume of blood, not necessitating manipulation of cells before testing, and using a phagocytic target relevant to the pathogenesis of HIV infection.
Exacerbation of invasive aspergillosis by the immunosuppressive fungal metabolite, gliotoxin
Authors: SUTTON PHILIP , WARING PAUL , MÜLLBACHER ARNO 
Published: June 2007

SummaryInvasive aspergillosis is a significant cause of death in immunocompromised individuals. The majority of strains of the main causative agent, Aspergillus fumigatus, produce gliotoxin, a secondary metabolite with demonstrated in vitro immunosuppressive activity. Pretreatment of normally resistant mice with a single injection of a sublethal dose of gliotoxin was sufficient to make them susceptible to infection and subsequent death, after challenge with A. fumigatus spores. Animals infected with the non‐gliotoxin producing strain survived significantly longer than those infected with a gliotoxin producer. We propose that the release of gliotoxin by A. fumigatus hyphae during infection can exacerbate the pathogenesis of aspergillosis.
Modulation of immune responses by bovine β‐casein
Authors: WONG CHUN W , SEOW HENG F , LIU AI H , HUSBAND ALAN J , SMITHERS GEOFFREY W , WATSON DENNIS L 
Published: June 2007

SummaryThe present study reports the influence of bovine β‐casein on in vitro and in vivo immune responses. Bovine β‐casein showed an inhibitory effect on ovine neutrophil chemotaxis but had an enhancing effect on superoxide production by neutrophils. In response to mitogenic stimulation, the proliferative response of both T and B lymphocytes was significantly enhanced by β‐casein. While β‐casein had no significant effects on IFNγ production by ovine blood lymphocytes, and TNFα production and MHC Class II antigen expression by ovine bronchoalveolar macrophages, it enhanced IL‐1β production by the macrophages. β‐casein also had no influence on bovine NK cell activity against a virally‐infected cell line. Interestingly, β‐casein was found to reduce the adjuvant effect of matrix immune stimulating complexes (ISCOM) on anti‐ovalbumin antibody response in mice when given intramuscularly. Taken together, the results suggest that bovine β‐casein had selective modulating effects in vitro on both innate and adaptive immune responses in ruminants, whereas systemic administration of β‐casein, that might have a depressive effect on adjuvant activity, requires further study.
Endogenous presentation of a nascent antigenic epitope to CD8+ CTL is more efficient than exogenous presentation
Authors: HAHN YOUNG S , HAHN CHANG S , BRACIALE THOMAS J 
Published: June 2007

SummaryCytotoxic T lymphocytes (CTL) recognize short antigenic peptides in association with class I MHC molecules at the cell surface. Newly synthesized viral polypeptides are processed in the cytoplasm and the fragments of antigen are transported into the endoplasmic reticulum (ER) via a peptide transporter where they complex with nascent class I molecules. The peptide‐MHC complex is transported to the cell surface and presented to CTL. Sequence analysis of endogenously expressed, MHC‐associated self or viral antigens indicates that the naturally processed peptides bound to class I MHC molecules are in general 9 ± 1 residues long. Peptides bound to specific class I MHC molecules have in common allele‐specific motifs of conserved residues. The motif for the class I Kd molecules has been shown to be nine or 10 residues with the sequence X‐Tyr‐(X)6‐I/L or X‐Tyr‐(X)7‐I/L. The Tyr residue at the second position and the I/L residue at the ninth position are allele‐specific anchor residues which appear to be required for binding of the peptide to Kd. To examine the stringency of the requirement for Tyr at the second position, we have performed saturation mutagenesis of a minigene encoding the class I Kd‐restricted influenza HA210‐219 site at the Tyr residue 211. A series of 10 mutants was tested for effects on target‐cell sensitization. Most amino acid substitutions for the Tyr residue resulted in a loss of endogenous peptide recognition by HA210‐219 reactive CTL, consistent with the critical role of the Tyr at the second position for interaction with Kd molecules. One mutant gene‐product encoding a His substitution for the Tyr residue was recognized by CTL. However, the corresponding synthetic peptide containing a His substitution at the dominant anchor position bound only weakly to Kd, and target cells treated with the peptide were poorly recognized by CTL. The endogenous His‐containing peptide was also less stably associated with class I MHC Kd molecules at the cell surface than the wild‐type Tyr peptide. These data indicate that endogenous antigenic peptides may bind newly‐synthesized class I MHC molecules in the ER more efficiently than fully formed class I molecules at the cell surface and that endogenous peptides may dissociate from class I MHC molecules at different rates. The implications of these findings for CTL recognition and epitope mapping are discussed.
Regulation of autoimmune diabetes: Characteristics of non‐islet‐antigen specific therapies
Authors: GAZDA LAWRENCE S , BAXTER ALAN G , LAFFERTY KEVIN J 
Published: June 2007

SummaryNon‐islet‐antigen specific treatments have been shown to alter the natural history of insulin dependent diabetes in both the non‐obese diabetic (NOD) mouse and in recently diagnosed patients. However, concerns have been raised regarding the possibility that non‐islet‐antigen specific therapy may trade cell mediated autoimmunity for antibody dependent autoimmunity. Female NOD mice at approximately 70 days of age were treated with the non‐islet‐antigen specific agents complete Freund's adjuvant (CFA) and Bacillus Calmette‐Guérin (BCG) and assayed for the development of antibody mediated autoimmunity at 300 days of age. Autoantibodies to red cells were not detected in any of the BCG (n= 19) or CFA (n= 15) treated animals, while 2 of 13 age‐matched NOD animals had autoantibodies to red cells, shown by a positive direct Coomb's test. Anti‐nuclear autoantibodies and complement deposition in the renal glomeruli were not significantly increased in the treated animals as compared to age‐matched non‐diabetic mice. The relative effectiveness of CFA and BCG treatment was examined in terms of the ability of these agents to preserve insulin containing islets. Complete Freund's adjuvant treatment was found to be more effective in preserving insulin containing islets when compared to BCG treatment. This study demonstrates that it is possible to inhibit the development of autoimmune diabetes without increasing the probability that treated animals will develop antibody dependent autoimmunity.
Expression of the recombinase‐activating gene (RAG‐1) in murine early embryogenesis
Authors: HAYAKAWA SATOSHI , TOCHIGI MEIJIN , CHISHIMA FUMIHISA , SHIRAISHI HISAMI , TAKAHASHI NORIKO , WATANABE KOH , FUJII KIYOSHI T , SATOH KAZUO 
Published: June 2007

SummaryThe recombinase activation genes, RAG‐1 and RAG‐2, are expressed together in immature T or B lymphocytes and possess activity to induce V(D)J rearrangement in T cell receptor (TCR) and Ig genes. In vertebrates, only Ig and TCR molecules are reported to have recombination in their development using multiple V, D, J component gene segments. Thus, expression of RAG genes are localized only in lymphoid organs and sites of extrathymic T cell differentiation. In this study, we have used RAG‐1 and RAG‐2 genes as markers of possible genetic recombination in developing murine preimplanation embryos, using the highly sensitive reverse transcriptase polymerase chain reaction (RT‐PCR) technique and in situ hybridization. From 40 preimplantation embryos of various developmental stages we extracted RNA. reverse‐transcribed it into cDNA and used it in RT‐PCR studies. A PCR of 35 cycles disclosed expression of RAG‐1 but not RAG‐2 in morulae and blastocysts. Southern blot hybridization using a specific synthetic oligonucleotide probe for RAG‐1 and RT‐PCR with another primer pair identified RAG‐1 expression in developing embryos. In situ hybridization using a cooled CCD camera also revealed localization of RAG‐1 mRNA in blastocysts. We propose possible genetic recombination during late preimplantation murine embryogenesis which may contribute to the loss of totipotency and differentiation of inner cell mass and trophoectoderm.
In vivo studies of macrophages and intercellular adhesion molecule‐1 following lipopolysaccharide treatment in tumourbearing rats
Authors: NILSSON TM , WOODS AE , ROFE AM 
Published: June 2007

SummaryHistological, haematological and immunocytochemical analyses were performed on a mammary adenocarcinoma implanted in Dark Agouti rats treated with LPS to further elucidate the role of TNF‐α in tumour biology. Tumours were examined 4–12 days after implantation with parallel studies on rats treated with LPS (200μg/100g bodyweight [b.w.J) 24 h before removal. Tumour tissue from rats with 12‐day‐old lesions was also examined over the 24 h period after LPS administration. Haemorrhagic necrosis was evident 6 h after endotoxin treatment and became profound by 24 hours, at which stage only a thin band of viable cells was seen at the rim of the tumour. Using immunocytochemical techniques and a monoclonal anti‐macrophage antibody, macrophage numbers were seen to increase throughout the tumour following LPS administration at each stage of tumour growth. Immunocytochemical staining for intercellular adhesion molecule‐1 (ICAM‐I), an adhesion molecule normally involved in monocyte recruitment, could not be detected in vascular channels within the tumours investigated. However, subcutaneous vessels at the tumour periphery produced a strong linear reaction. The results show that macrophage numbers in tumours increase after LPS administration, concurrently with the development of haemorrhagic necrosis. This cellular infiltration was associated with peripheral monocytopenia. ICAM‐I expression on the vascular endothelium within tumours was deficient.