Viral Infection Results in Massive CD8+ T Cell Expansion and Mortality in Vaccinated Perforin-Deficient Mice

AbstractPerforin-mediated cytotoxicity is essential for clearance of primary LCMV infection. BALB/c-perforin-deficient (PKO) mice survived LCMV infection by deleting NP118-specific CD8+ T cells whereas vaccination of PKO mice with Listeria expressing NP118 generated a stable memory CD8+ T cell population. However, >85% of vaccinated BALB/c-PKO mice died after LCMV infection. Mortality was associated with enormous expansion of NP118-specific CD8+ T cells in both lymphoid and nonlymphoid tissues and aberrant CD8+ T cell cytokine production. Depletion of CD8+ T cells or treatment with anti-IFNγ antibody rescued vaccinated mice from mortality. Thus, perforin was essential for resistance to secondary LCMV infection, and, in the absence of perforin, vaccination resulted in lethal disease mediated by dysregulated CD8+ T cell expansion and cytokine production

Differential Role of “Signal 3” Inflammatory Cytokines in Regulating CD8 T Cell Expansion and Differentiation in vivo

Following an infection, naïve CD8 T cells are stimulated by dendritic cells (DC) displaying pathogen-derived peptides on MHC class I molecules (signal 1) and costimulatory molecules (signal 2). Additionally, pathogen-induced inflammatory cytokines also act directly on the responding CD8 T cells to regulate their expansion and differentiation. In particular, both type I interferons (IFNs) and IL-12 have been described as critical survival signals (signal 3) for optimal CD8 T cell accumulation during the expansion phase. Furthermore, expansion in numbers of antigen-specific CD8 T cells is coupled with their acquisition of effector functions to combat the infection. However, it still remains unclear whether these same cytokines also regulate the effector/memory differentiation program of the CD8 T cell response in vivo. Here, we demonstrate that defective signaling by either type I IFNs or IL-12 to the responding CD8 T cells impairs maximal expansion in response to DC immunization + CpG ODN, but neither of these cytokines is essential to regulate the effector/memory differentiation program. In addition, lack of direct IL-12 signaling to CD8 T cells accelerates the development of central memory phenotype in both primary and secondary antigen-specific memory CD8 T cells

Legendary landscapes: a cultural geography of the Paul Bunyan and Blue Ox phenomena of the North woods

Doctor of PhilosophyDepartment of GeographyKaren J. De BresLandscapes express much of who we are. Our history, thoughts, and values are all interwoven into cultural landscape features. By researching the landscape similarities and dissimilarities on the regional level, geographers are able to learn more about a people's identity. Scattered across the vast expanses of the Northwoods, residents and visitors alike are greeted by representations of a lumberjack and his blue ox. In addition to large statues of Paul Bunyan and the Blue Ox, festivals, sporting events, businesses, and public lands are all named in honor of the two folk giants. These features are so prevalent and well known that references to the region by those who live outside the Northwoods often begin by acknowledging the folk heroes. This study explains the relationship between Paul Bunyan and the Northwoods region. Focusing on the area of northern Minnesota between the towns of Bemidji and Brainerd, qualitative research methods were conducted over a four-year period (2004-2007) to better understand the phenomena. Since the 1930s, residents of the Northwoods have used Paul Bunyan and Babe the Blue Ox landscape features to celebrate symbolically the region’s golden age of logging. These representations have evolved over the years to include both public and private landscape features. Given the level of permanence of many of the items as well as the authenticity, popularity, and attachment local residents express towards Paul and Babe, cultural landscape features of the lumberjack and his blue ox will continue to be seen as an integral component of the Northwoods regional identity

Integrating Building Information Modeling and Health and Safety for Onsite Construction

Background: Health and safety (H&S) on a construction site can either make or break a contractor, if not properly managed. The usage of Building Information Modeling (BIM) for H&S on construction execution has the potential to augment practitioner understanding of their sites, and by so doing reduce the probability of accidents. This research explores BIM usage within the construction industry in relation to H&S communication. Methods: In addition to an extensive literature review, a questionnaire survey was conducted to gather information on the embedment of H&S planning with the BIM environment for site practitioners. Results: The analysis of responses indicated that BIM will enhance the current approach of H&S planning for construction site personnel. Conclusion: From the survey, toolbox talk will have to be integrated with the BIM environment, because it is the predominantly used procedure for enhancing H&S issues within construction sites. The advantage is that personnel can visually understand H&S issues as work progresses during the toolbox talk onsite

The relevance of non-human primate and rodent malaria models for humans

At the 2010 Keystone Symposium on "Malaria: new approaches to understanding Host-Parasite interactions", an extra scientific session to discuss animal models in malaria research was convened at the request of participants. This was prompted by the concern of investigators that skepticism in the malaria community about the use and relevance of animal models, particularly rodent models of severe malaria, has impacted on funding decisions and publication of research using animal models. Several speakers took the opportunity to demonstrate the similarities between findings in rodent models and human severe disease, as well as points of difference. The variety of malaria presentations in the different experimental models parallels the wide diversity of human malaria disease and, therefore, might be viewed as a strength. Many of the key features of human malaria can be replicated in a variety of nonhuman primate models, which are very under-utilized. The importance of animal models in the discovery of new anti-malarial drugs was emphasized. The major conclusions of the session were that experimental and human studies should be more closely linked so that they inform each other, and that there should be wider access to relevant clinical material