This directory has become a valued source of information for energy-efficient building designers and specifiers throughout Europe and the details and scope of product, service and supplier listings ...have again been extensively updated for this edition.
Introduction * Preface * Solar and Climatic Design * Photovoltaics and Solar Thermal * Integrated Design * Energy Conservation * Sustainable Building and Materials Selection * Energy Efficient Building Services and Controls * Software/Resources * Listings
Editorial Board: Owen Lewis and John Goulding, Energy Research Group, School of Architecture, University College Dublin, Ireland.
Background. Previous studies have shown that the interaction of CD200R, a myeloid inhibitory receptor, with its ligand, CD200, is critical in the control of innate immune activation in the lung. ...Methods and Results. Using a mouse model of bacterial superinfection following influenza, we show that an absence of CD200R (a negative regulator highly expressed by macrophages and dendritic cells), restricts commensal and exogenous bacterial invasiveness and completely prevents the mortality observed in wild-type mice. This benefit is due to a heightened innate immune response to influenza virus in cd200r knockout mice that limits immune pathogenesis and viral load. In wild-type mice, apoptotic cells expressing CD200 that we believe contribute to the suppressed innate immune response to bacteria dominate during the resolution phase of influenza-induced inflammation. We also show for the first time the presence of a variety of previously unidentified bacterial species in the lower airways that are significantly adjusted by influenza virus infection and may contribute to the pathophysiology of disease. Conclusions. The interaction of CD200 with CD200R therefore contributes to the hyporesponsive innate immune state following influenza virus infection that predisposes to secondary bacterial infection, a phenomenon that has the potential for immune modulation.
The lung must maintain a high threshold of immune 'ignorance' to innocuous antigens to avoid inflammatory disease that depends on the balance of positive inflammatory signals and repressor pathways. ...We demonstrate here that airway macrophages had higher expression of the negative regulator CD200 receptor (CD200R) than did their systemic counterparts. Lung macrophages were restrained by CD200 expressed on airway epithelium. Mice lacking CD200 had more macrophage activity and enhanced sensitivity to influenza infection, which led to delayed resolution of inflammation and, ultimately, death. The administration of agonists that bind CD200R, however, prevented inflammatory lung disease. Thus, CD200R is critical for lung macrophage immune homeostasis in the resting state and limits inflammatory amplitude and duration during pulmonary influenza infection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Innate immune cells including macrophages, dendritic cells, and granulocytes are resident within or patrol very different microenvironments in the host. Their activity or responsiveness to ...antigen is dictated by site-specific factors. Because of the constant exposure to environmental antigens and commensal microorganisms, mucosal immunity needs to be more constrained than peripheral counterparts to prevent unnecessary inflammation. The epithelial surfaces that dominate all mucosal tissues provide an ideal regulator since innate immune cells are often in intimate contact with, or lie immediately beneath, them and a breach in epithelial integrity would signal a damaging event and release innate immunity from their influence. We discuss the role of the respiratory epithelium in raising the threshold of innate immune cell activation at homoeostasis, how its absence triggers innate immunity, and how inflammatory resolution often produces an altered homoeostatic environment that can affect the next inflammatory event at this site.
Abstract Innate immunity at mucosal surfaces requires additional restraint to prevent inflammation to innocuous antigens or commensal microorganisms. The threshold above which airway macrophages ...become activated is raised by site-specific factors including the receptors for transforming growth factor beta, interleukin 10 and CD200; the ligands for which are produced by, or expressed on, respiratory epithelium. We discuss such site-specific regulation and how this is continually altered by prior infections. Resetting of innate reactivity represents a strategy for limiting excessive inflammation, but in some may pre-dispose to secondary bacterial pneumonia.
The differentiation of helper T cells into effector subsets is critical to host protection. Transcription factors of the E-protein and Id families are important arbiters of T cell development, but ...their role in the differentiation of the TH1 and TFH subsets of helper T cells is not well understood. Here, TH1 cells showed more robust Id2 expression than that of TFH cells, and depletion of Id2 via RNA-mediated interference increased the frequency of TFH cells. Furthermore, TH1 differentiation was blocked by Id2 deficiency, which led to E-protein-dependent accumulation of effector cells with mixed characteristics during viral infection and severely impaired the generation of TH1 cells following infection with Toxoplasma gondii. The TFH cell-defining transcriptional repressor Bcl6 bound the Id2 locus, which provides a mechanism for the bimodal Id2 expression and reciprocal development of TH1 cells and TFH cells.
IL-9 is a cytokine of great current interest associated with allergic/Th2 responses. High levels of IL-9 are present in bronchial secretions from infants with respiratory syncytial virus (RSV) ...bronchiolitis. To test its effects in RSV disease with a Th2 profile, BALB/c mice were vaccinated with recombinant vaccinia virus expressing the RSV G protein. On RSV challenge, immunized mice developed augmented disease characterized by enhanced pulmonary Th2 and local IL-9 production peaking on days 7-10 of RSV infection. Depletion with anti-IL-9 Ab at vaccination or RSV challenge enhanced viral clearance. Depletion only at challenge had no effect on disease severity, whereas depletion at immunization and challenge enhanced Th1 responses, inhibited virus-specific IgG1 production, and enhanced disease severity. By contrast, depletion of IL-9 at immunization boosted IgG2a and inhibited the Th2 response and disease during subsequent infection without a concomitant increase in type 1 cytokines. Adoptive transfer of secondary memory CD4 T cells from the spleens of IL-9-depleted mice into naive recipients replicated many of the effects of depletion, indicating that IL-9 acts via CD4 T cells. Therefore, IL-9 is a previously unknown but key modulator of antiviral immunity, regulating T and B cell responses and having potent and specific effects on viral lung disease.
Evaluation of: Morens DM, Taubenberger JK, Fauci AS: Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness. J. Infect. ...Dis. 198(7), 962-970 (2008). Secondary bacterial pneumonia is a common occurrence following lung influenza virus infection and leads to a significantly worse prognosis. This recent re-analysis of postmortem specimens and a vast number of reports from past influenza pandemics shows an extremely high frequency of lung colonization by bacterial species that are commonly found in the nasopharynx. This polymicrobial condition occurred in the preantibiotic era 1918-1919 influenza pandemic, but there is also evidence of bacterial co-infections in those outbreaks that occurred after antibiotic introduction. As such, antibiotic treatment should be included in any pandemic preparedness strategy. However, the choice of which antibiotic to use is important since some may even heighten morbidity and mortality.
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