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As research faculty with expertise in the area of host-pathogen interactions (HPI), we used a research group model to effect our professional development as scientific educators. We have established a working hypothesis: The implementation of a curriculum that forms bridges between our seven HPI courses allows our students to achieve deep and meaningful learning of HPI concepts. Working collaboratively, we identified common learning goals, and we chose two microorganisms to serve as anchors for student learning. We instituted variations of published active-learning methods to engage students in research-oriented learning. In parallel, we are developing an assessment tool. The value of this work is in the development of a teaching model that successfully allowed faculty who already work collaboratively in the research area of HPI to apply a "research group approach" to further scientific teaching initiatives at a research university. We achieved results that could not be accomplished by even the most dedicated instructor working in isolation. (Contains 2 tables.)

The adaptive immune system is equipped to eliminate both tumors and pathogenic microorganisms. It requires a series of complex and coordinated signals to drive the activation, proliferation, and differentiation of appropriate T cell subsets. It is now established that changes in cellular activation are coupled to profound changes in cellular metabolism. In addition, emerging evidence now suggest that specific metabolic alterations associated with distinct T cell subsets may be ancillary to their differentiation and influential in their immune functions. The "Warburg effect" originally used to describe a phenomenon in which most cancer cells relied on aerobic glycolysis for their growth is a key process that sustain T cell activation and differentiation. Here, we reviewhowdifferent aspects of metabolism in T cells influence their functions, focusing on the emerging role of key regulators of glucose metabolism such as HIF-1α. A thorough understanding of the role of metabolism in T cell function could provide insights into mechanisms involved in inflammatory-mediated conditions, with the potential for developing novel therapeutic approaches to treat these diseases. [ABSTRACT FROM AUTHOR]

Because of the cytotoxic potential of CD8+ T cells, maintenance of CD8+ peripheral tolerance is extremely important. A major peripheral tolerance mechanism is the induction of anergy, a refractory state in which proliferation and IL-2 production are inhibited. We used a TCR transgenic mouse model to investigate the signaling defects in CD8+ T cells rendered anergic in vivo. In addition to a previously reported alteration in calcium/NFAT signaling, we also found a defect in NF-κB-mediated gene transcription. This was not due to blockade of early NF-κB activation events, including IκB degradation and NF-κB nuclear translocation, as these occurred normally in tolerant T cells. However, we discovered that anergic cells failed to phosphorylate the NF-κB p65 subunit at Ser311 and also failed to acetylate p65 at Lys310. Both of these modifications have been implicated as critical for NF-κB transactivation capacity, and thus, our results suggest that defects in key phosphorylation and acetylation events are important for the inhibition of NF-κB activity (and subsequent T cell function) in anergic CD8+ T cells. [ABSTRACT FROM AUTHOR]

Abstract: The establishment and maintenance of T cell tolerance to self- and non-pathogenic foreign antigens is critical for immune homeostasis. Thymic deletion of self-reactive T cells is an important component of tolerance, but it is incomplete, and does not establish tolerance to most foreign antigens. Thus, mechanisms of peripheral tolerance are also required. This is especially true for CD8+ T cells, which are able to encounter their cognate antigens presented by nearly any cell type. Upon differentiating into cytotoxic T lymphocytes (CTL), CD8+ T cells do not require costimulation for their cytotoxic function, reinforcing the importance of tolerance in these cells. In this review, we will discuss the modes of peripheral tolerance in CD8+ T cells, covering both naïve and effector T cells. We will examine the antigen and signaling requirements for tolerance induction and maintenance, and will also touch on similarities and potential differences between CD8+ and CD4+ tolerance mechanisms. [Copyright &y& Elsevier]

Summary: The Bcl-2-associated X protein (Bax) and Bcl-2-antagonist/killer (Bak) are essential regulators of lymphocyte apoptosis, but whether they play a role in viable T cell function remains unclear. Here, we report that T cells lacking both Bax and Bak display defects in antigen-specific proliferation because of Ca2+-signaling defects. Bax−/−, Bak−/− T cells displayed defective T cell receptor (TCR)- and inositol-1,4,5-trisphosphate (IP3)-dependent Ca2+ mobilization because of altered endoplasmic reticulum (ER) Ca2+ regulation that was reversed by Bax''s reintroduction. The ability of TCR-dependent Ca2+ signals to stimulate mitochondrial NADH production in excess of that utilized for ATP synthesis was dependent on Bax and Bak. Blunting of Ca2+-induced mitochondrial NADH elevation in the absence of Bax and Bak resulted in decreased reactive-oxygen-species production, which was required for T cell proliferation. Together, the data establish that Bax and Bak play an essential role in the control of T cell proliferation by modulating ER Ca2+ release. [Copyright &y& Elsevier]

This essay describes how the use of a concept inventory has enhanced professional development and curriculum reform efforts of a faculty teaching community. The Host Pathogen Interactions (HPI) teaching team is composed of research and teaching faculty with expertise in HPI who share the goal of improving the learning experience of students in nine linked undergraduate microbiology courses. To support evidence-based curriculum reform, we administered our HPI Concept Inventory as a pre- and postsurvey to approximately 400 students each year since 2006. The resulting data include student scores as well as their open-ended explanations for distractor choices. The data have enabled us to address curriculum reform goals of 1) reconciling student learning with our expectations, 2) correlating student learning with background variables, 3) understanding student learning across institutions, 4) measuring the effect of teaching techniques on student learning, and 5) demonstrating how our courses collectively form a learning progression. The analysis of the concept inventory data has anchored and deepened the team's discussions of student learning. Reading and discussing students' responses revealed the gap between our understanding and the students' understanding. We provide evidence to support the concept inventory as a tool for assessing student understanding of HPI concepts and faculty development.