Active Learning and Technology Approaches for Teaching Immunology to Undergraduate Students.

Immunology is a fascinating and extremely complex field, with natural connections to many disciplines both within STEM and beyond. Teaching an undergraduate course in immunology therefore provides both opportunities and challenges. Significant challenges to student learning include mastering the volume of new vocabulary and figuring out how to think coherently about a physiological system that is so anatomically disseminated. More importantly, teaching immunology can be complicated because it requires students to integrate knowledge derived from prior introductory courses in a range of fields, including cell biology, biochemistry, anatomy and genetics. However, this also provides an opportunity to use the study of the immune system as a platform on which students can assemble and integrate foundational STEM knowledge, while also learning about a new and exciting field. Pedagogical theory has taught us that students learn best by engaging with complicated questions and by thinking metacognitively about how to approach solutions. Building this skill set in today's students, who now hail from a broad demographic and who are accustomed to acquiring their knowledge from a variety of different media, requires a new set of teaching tools. Using perspectives from four different immunology educators, we describe a range of student-centered, active learning approaches that have been field-tested in a number of different immunology classrooms and that are geared to a variety of learning styles. In this paper, we explore the hypothesis that active learning approaches to immunology improve comprehension and retention by increasing student engagement in class and their subsequent mastery of complex topics.

Regulation of intracellular pH in human melanoma: potential therapeutic implications.

Melanoma cells in vivo maintain intracellular pH (pHi) in a viable range despite an extracellular tumor pH (pHe) that is typically below 7.0. In general, three families of transporters are capable of removing metabolic protons, but the specific transporters responsible for the maintenance of pHi at low pHe in melanomas have not been identified. Although the transporters exist in most cells, an inhibitor would be predicted to have selectivity for cells located in an acidic tumor bed because cells in that environment would be expected to have transporters chronically activated. In this report, the levels and extent of expression of the Na+/H+ exchanger (NHE-1) and two of the H+-linked monocarboxylate transporters (MCTs) were evaluated in three melanoma cell lines. The effects of inhibitors of each transporter were tested at an extracellular pH (pHe) of 7.3, 6.7, or 6.5 in melanoma cells that were grown at pHe 7.3 or 6.7. The activity of MCT isoform 1 (MCT-1) was up-regulated in three melanoma cell lines at low pHe, but that of NHE-1 was not. Furthermore, NHE-1 activity was lower in the melanomas than in other normal and malignant cell lines that were tested. Reverse transcription-PCR using primers specific for MCT-1, MCT-4, and NHE-1 showed that expression of none of these transporters was reproducibly up-regulated at the level of transcription when cells were grown at pHe 6.7 instead of pHe 7.3. Ex vivo experiments using DB-1 human melanoma xenografts grown in severe combined immunodeficient mice found that MCT-1 and not NHE-1 was a major determinant of DB-1 tumor cell pHi. Taken together, the data indicate that MCTs are major determinants of pH regulation in melanoma. In contrast, keratinocytes and melanocytes under low pHe conditions relied on NHE-1. Inhibitors of MCTs thus have great potential to improve the effectiveness of chemotherapeutic drugs that work best at low pHi, such as alkylating agents and platinum-containing compounds, and they should be selective for cells in an acidic tumor bed. In most tissues, it is proposed that the NHE-1 could compensate for an inhibited MCT to prevent acidification, but in melanoma cells this did not occur. Therefore, MCT inhibitors may be particularly effective against malignant melanoma.