Transmission of maternal immunity in pigs and ruminants after birth

In swine and ruminants, maternal immunoglobulins (Ig) do not reach the foetus before birth. In these species, passive immunity is transferred via the colostrum rich in IgG, which cross the newborn’s intestinal wall due to a temporary non-selective permeability. The newborn’s protection against pathogens is therefore provided initially by these colostral immunoglobulins, then by milk immunoglobulins, mainly IgG1 in ruminants and IgA in swine. In swine, IgA plasmocytes are generated by inducer sites in the intestine (Peyer’s patches) and in the upper airways (nasal mucosa, tonsils). These cells migrate to the mammary glands where they are recruited by vascular addressins and chemokines. This process provides a far greater excretion of IgA than the simple filtration of serum IgA. In ruminants, the lack of such addressins in the mammary gland explains the low levels of IgA plasmocytes in this organ. In these animals, both colostral and lactogenic immunity are provided by IgG1 filtered from the blood into the milk. Consequently, the improvement of colostral immunity in both species (IgG in swine and IgG1 in ruminants), and of lactogenic immunity in ruminants (IgG1) depends on the stimulation of the maternal systemic immune system, whereas the improvement of lactogenic immunity in swine (IgA) depends on the stimulation of the maternal mucosal inducer sites.Chez les porcins et les ruminants, l'absence de transfert prénatal d'immunoglobulines (Ig) est compensée par un colostrum enrichi en IgG qui traversent la paroi intestinale du nouveau-né à la faveur d'une perméabilité non sélective et temporaire. La protection du nouveau-né contre les invasions d'agents pathogènes est donc assurée dans un premier temps par les immunoglobulines colostrales, et ensuite par celles du lait, principalement des IgG1 chez les ruminants et des IgA chez le porc. Chez le porc, les plasmocytes à IgA sont générés dans des sites inducteurs au niveau de l'intestin (plaques de Peyer) et des voies aériennes supérieures (muqueuse nasale, amygdales pharyngiennes). Ils migrent ensuite vers la glande mammaire où ils sont recrutés par des adressines vasculaires et des chimiokines. Ce processus permet une excrétion bien plus importante d'IgA que la seule filtration des IgA sériques. Chez les ruminants, l'absence de ces adressines dans la glande mammaire explique la rareté des plasmocytes à IgA dans cet organe. Chez cette espèce, ce sont plutôt les IgG1 filtrées depuis le sang maternel vers le lait qui assurent l'immunité colostrale et lactée du nouveau-né. L'amélioration de l'immunité colostrale chez ces deux espèces (IgG chez le porc et IgG1 chez les ruminants), et de l'immunité lactée chez les ruminants (lgG1) dépend donc de la stimulation de l'immunité systémique maternelle, tandis que l'amélioration de l'immunité lactée chez le porc (IgA) dépend de la stimulation des sites inducteurs muqueux

Pharmacokinetics in vivo and pharmacodynamics ex vivo/in vitro of meropenem and cefpirome in the Yucatan micropig model: continuous infusion versus intermittent injection

ObjectiveTo investigate the pharmacodynamic disposition of two recently developed β-lactam antibiotics, meropenem and cefpirome, in the Yucatan micropig model, and to compare the bactericidal activity of these drugs against bacteria in this in vitro/ex vivo micropig model after administration by both intermittent injection and continuous infusion.MethodsCefpirome (1 g) was given to the micropig over a 12-h period by direct intravenous injection and 6-h continuous infusion (500 mg). Meropenem (250 mg) was administered either by 30-min intravenous and 8-h continuous infusion. The two drugs were assayed by HPLC. The pharmacodynamics of these drugs were evaluated by means of (1) serum killing curve against Klebsiella pneumoniae producing extended-spectrum β-lactamase, stably derepressed Enterobacter cloacae and methicillin-susceptible penicillinase-producing Staphylococcus aureus, and (2) calculations of index of surviving bacteria (ISB).ResultsThe bactericidal activity of meropenem against K. pneumoniae and E. cloacae in this in vitro/ex vivo model was excellent, with a 4 log decrease at peak concentrations. Meropenem produced a mixed concentration- and time-dependent, killing effect against E. cloacae and K. pneumoniae. The ISB value ranged from 25% to 30% for E. cloacae. With concentrations above MIC for S. aureus (1 mg/L), cefpirome has a time-dependent bactericidal activity, as shown by the ISB ranging from 20% to 80% after 4 h and between 20% and 40% after an 8-h drug exposure. For both antibiotics, the higher concentrations obtained just after intermittent injection had a rapid and strong killing effect against the strains tested, but the trough levels had no bactericidal activity. The continuous infusions produce consistent concentrations of antibiotic that can be maintained above the MIC, and the bactericidal activity of which ranges from 2 to 4 log10 decrease of inoculum.ConclusionsIn the present study the micropig has been shown to be an adequate model for the pharmacodynamic investigation of cefpirome and meropenem. In general, continuous infusion appears to optimize the pharmacodynamic profile of the two tested β-lactam antibiotics. However, against Gram-negative bacilli, the administration of a loading dose prior to continuous infusion of β-lactams would eliminate the only potential pharmacokinetic disadvantage of continuous infusion and ensure the rapid onset of antimicrobial activity

Effect of Saccharomyces cerevisiae var. Boulardii and b-galactomannan oligosaccharide on porcine intestinal epithelial and dendritic cells challenged in vitro with Escherichia coli F4 (K88)

Probiotic and prebiotics, often called “immune-enhancing” feed additives, are believed to deal with pathogens, preventing the need of an immune response and reducing tissue damage. In this study, we investigated if a recently developed b-galactomannan (bGM) had a similar protective role compared to Saccharomyces cerevisiae var. Boulardii (Scb), a proven probiotic, in the context of enterotoxigenic Escherichia coli (ETEC) infection. ETEC causes inflammation, diarrhea and intestinal damage in piglets, resulting in large economic loses worldwide. We observed that Scb and bGM products inhibited in vitro adhesion of ETEC on cell surface of porcine intestinal IPI-2I cells. Our data showed that Scb and bGM decreased the mRNA ETEC-induced gene expression of pro-inflammatory cytokines TNF-a, IL-6, GM-CSF and chemokines CCL2, CCL20 and CXCL8 on intestinal IPI-2I. Furthermore, we investigated the putative immunomodulatory role of Scb and bGM on porcine monocyte-derived dendritic cells (DCs) per se and under infection conditions. We observed a slight up-regulation of mRNA for TNF-a and CCR7 receptor after coincubation of DC with Scb and bGM. However, no differences were found in DC activation upon ETEC infection and Scb or bGM co-culture. Therefore, our results indicate that, similar to probiotic Scb, prebiotic bGM may protect intestinal epithelial cells against intestinal pathogens. Finally, although these products may modulate DC activation, their effect under ETEC challenge conditions remains to be elucidated.This work was supported by grants from the French National Institute for Agricultural Research (INRA, France) and grant AGL 2009-11936 of the Ministerio de Ciencia e Innovación (MICIIN, Spain). We gratefully acknowledge Dr I. Badiola (CReSA) for providing ETEC GN1034 strain and Dr J. Domínguez-Juncal (Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, INIA, Madrid, Spain) for kindly providing antibodies for pig cell surface markers.info:eu-repo/semantics/publishedVersio

Action de certains serums hétérologues antithymus animaux sur les leucocytes de sujets normaux et leucémiques. (Note préliminaire)

Les sérums antithymus de veau et de porc préparés sur le cheval exercent sur les leucocytes de sujets atteints de leucémie aiguë lymphoblastique, une activité cytotoxique nettement supérieure à celle constatée sur les lymphocytes normaux de donneurs apparte nant aux groupes sanguins A et 0. Les sérums antithymus de porc et de cheval préparés sur le mouton sont sans effet sur les lympho cytes de sujets sains mais ont une action sur les leucocytes de malades atteints de leucémie aiguë lymphoblastique. Le sérum de mouton antithymus de porc se montre également actif sur les leuco cytes de malades atteints de leucémie aiguë myéloblastique. S’ajou tant à la fragilité accrue des cellules malades, la présence ou la plus grande abondance d’antigènes communs aux cellules thymiques animales et à certains leucocytes « leucémiques », dans l’interpréta tion du phénomène, est discutée

Commensal Bacteria and Expression of Two Major Intestinal Chemokines, TECK/CCL25 and MEC/CCL28, and Their Receptors

Background: CCL25/TECK and CCL28/MEC are CC chemokines primarily expressed in thymic dendritic cells and mucosal epithelial cells. Their receptors, CCR9 and CCR10, are mainly expressed on T and B lymphocytes. In human, mouse, pig and sheep CCL25 and CCL28 play an important role in the segregation and the compartmentalization of the mucosal immune system. As evidenced by early comparisons of germ-free and conventional animals, the intestinal bacterial microflora has a marked effect on host intestinal immune functions. However, little is known about the impact of bacterial colonization on constitutive and induced chemokine expressions as well as on the generation of anti-inflammatory mechanisms. [br/] Methodology/Principal Findings: Therefore, we decided to focus by qPCR on the mRNA expression of two main gut chemokines, CCL25 and CCL28, their receptors CCR9 and CCR10, the Tregs marker Foxp3 and anti-inflammatory cytokines TGF-beta and IL-10 following colonization with different bacterial species within the small intestine. To accomplish this we used an original germ-free neonatal pig model and monoassociated pigs with a representative Gram-negative (Escherichia coli) or Gram-positive (Lactobacillus fermentum) commensal bacteria commonly isolated from the neonatal pig intestine. Our results show a consistent and marked effect of microbial colonization on the mRNA expression of intestinal chemokines, chemokine receptors, Foxp3 and TGF-beta. Moreover, as evidenced by in vitro experiments using two different cell lines, the pattern of regulation of CCL25 and CCL28 expression in the gut appears complex and suggests an additional role for in vivo factors. [br/] Conclusions/Significance: Taken together, the results highlight the key role of bacterial microflora in the development of a functional intestinal immune system in an elegant and relevant model for human immune system development

Early immune response following Salmonella enterica subspecies enterica serovar Typhimurium infection in porcine jejunal gut loops

Salmonella enterica subspecies enterica serovar Typhimurium, commonly called S. Typhimurium, can cause intestinal infections in humans and various animal species such as swine. To analyze the host response to Salmonella infection in the pig we used an in vivo gut loop model, which allows the analysis of multiple immune responses within the same animal. Four jejunal gut-loops were each inoculated with 3×108 cfu of S. Typhimurium in 3 one-month-old piglets and mRNA expressions of various cytokines, chemokines, transcription factors, antimicrobial peptides, toll like and chemokine receptors were assessed by quantitative real-time PCR in the Peyer’s patch and the gut wall after 24 h. Several genes such as the newly cloned CCRL1/CCX-CKR were assessed for the first time in the pig at the mRNA level. Pro-inflammatory and T-helper type-1 (Th1) cytokine mRNA were expressed at higher levels in infected compared to non-infected control loops. Similarly, some B cell activation genes, NOD2 and toll like receptor 2 and 4 transcripts were more expressed in both tissues while TLR5 mRNA was down-regulated. Interestingly, CCL25 mRNA expression as well as the mRNA expressions of its receptors CCR9 and CCRL1 were decreased both in the Peyer’s patch and gut wall suggesting a potential Salmonella strategy to reduce lymphocyte homing to the intestine. In conclusion, these results provide insight into the porcine innate mucosal immune response to infection with entero-invasive microorganisms such as S. Typhimurium. In the future, this knowledge should help in the development of improved prophylactic and therapeutic approaches against porcine intestinal S. Typhimurium infections

Maximising Social Interactions and Effectiveness within Distance Learning Courses: Cases from Construction

Advanced Internet technologies have revolutionised the delivery of distance learning education. As a result, the physical proximity between learners and the learning providers has become less important. However, whilst the pervasiveness of these technological developments has reached unprecedented levels, critics argue that the student learning experience is still not as effective as conventional face-to-face delivery. In this regard, surveys of distance learning courses reveal that there is often a lack of social interaction attributed to this method of delivery, which tends to leave learners feeling isolated due to a lack of engagement, direction, guidance and support by the tutor. This paper defines and conceptualises this phenomenon by investigating the extent to which distance-learning programmes provide the social interactions of an equivalent traditional classroom setting. In this respect, two distance learning case studies were investigated, covering the UK and Slovenian markets respectively. Research findings identified that delivery success is strongly dependent on the particular context to which the specific distance learning course is designed, structured and augmented. It is therefore recommended that designers of distance learning courses should balance the tensions and nuances associated with commercial viability and pedagogic effectiveness

Expression and immunogenicity of the mycobacterial Ag85B/ESAT-6 antigens produced in transgenic plants by elastin-like peptide fusion strategy.

International audienceThis study explored a novel system combining plant-based production and the elastin-like peptide (ELP) fusion strategy to produce vaccinal antigens against tuberculosis. Transgenic tobacco plants expressing the mycobacterial antigens Ag85B and ESAT-6 fused to ELP (TBAg-ELP) were generated. Purified TBAg-ELP was obtained by the highly efficient, cost-effective, inverse transition cycling (ICT) method and tested in mice. Furthermore, safety and immunogenicity of the crude tobacco leaf extracts were assessed in piglets. Antibodies recognizing mycobacterial antigens were produced in mice and piglets. A T-cell immune response able to recognize the native mycobacterial antigens was detected in mice. These findings showed that the native Ag85B and ESAT-6 mycobacterial B- and T-cell epitopes were conserved in the plant-expressed TBAg-ELP. This study presents the first results of an efficient plant-expression system, relying on the elastin-like peptide fusion strategy, to produce a safe and immunogenic mycobacterial Ag85B-ESAT-6 fusion protein as a potential vaccine candidate against tuberculosis

Literature review: an exploratory study

The increase in the number and quality of technologies has imposed on education in general new forms of learning, some with less relevance, but others with recognized results in the educational and scientific community. The Massive Open Online Courses (MOOC)are an example of one of these technologies with recognized results because that seems to contribute to the acquisition and mastery of digital competences in the context of the realization of the teaching-learning process supported by the networks. It is in these networks that all the participants in the educational process interact and collaborate with all, cultivate connections, debate the themes, present their criticisms, update their knowledge, acquire new skills, make decisions, but generically develop as members of a connectivist community. Based on these assumptions, in this research we intend to make a review of the literature to identify the aspects that, in detriment of regular education, to encourage the teachers to adopt the MOOC as technology for their professional development and to carry out the process of teaching and learning. Thus, through an exploratory research, characterized as documentary, we use the main sources of information, in this case scientific articles published on the subject to understand the relevance and contribution of the MOOC in an educational universe supported by technologies. In general, the results, although preliminary because of temporal limitations issues in accompanying the rapid evolution of the scientific production of knowledge, suggest that on the one hand the teachers opt for MOOC education for the ease of distance learning; on the other hand, adopt the MOOCs for the acquisition of digital skills oriented to the new challenges.info:eu-repo/semantics/publishedVersio

Patterns of debate in tertiary level asynchronous text-based conferencing

Argumentation can be defined at different levels and serve different purposes, but its role in knowledge understanding and construction has given it a central place in education, particularly at tertiary level. The advent of computer-supported text-based conferences has created new sites where such educational dialogues can take place, but the quality of the interaction and whether it is serving its educational purpose is still uncertain. This paper reports on a framework of analysis that has been developed to illuminate the arguing process within an asynchronous electronic conferencing environment, showing how it is both similar to, and different from, argumentation in the more traditional forums of multi-party, face-to-face discussion and traditional written essays. The framework develops earlier work by the authors and is applied to two electronic conferences within the same postgraduate course, comparing overall patterns of argumentation. Findings are presented on the extent to which the technology of electronic conferencing shapes and supports students’ participation in academic literacy practices relating to argumentation, proposing, at the same time, that the teaching strategy adopted by the lecturer is also an important variable