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.

Value, Access, and Cost of Cancer Care Delivery at Academic Cancer Centers.

Key challenges facing the oncology community today include access to appropriate, high quality, patient-centered cancer care; defining and delivering high-value care; and rising costs. The National Comprehensive Cancer Network convened a Work Group composed of NCCN Member Institution cancer center directors and their delegates to examine the challenges of access, high costs, and defining and demonstrating value at the academic cancer centers. The group identified key challenges and possible solutions to addressing these issues. The findings and recommendations of the Work Group were then presented at the Value, Access, and Cost of Cancer Care Policy Summit in September 2015 and multi-stakeholder roundtable panel discussions explored these findings and recommendations along with additional items.

Follicular dendritic cells, conduits, lymphatic vessels, and high endothelial venules in tertiary lymphoid organs: Parallels with lymph node stroma.

In this communication, the contribution of stromal, or non-hematopoietic, cells to the structure and function of lymph nodes (LNs), as canonical secondary lymphoid organs (SLOs), is compared to that of tertiary lymphoid tissue or organs (TLOs), also known as ectopic lymphoid tissues. TLOs can arise in non-lymphoid organs during chronic inflammation, as a result of autoimmune responses, graft rejection, atherosclerosis, microbial infection, and cancer. The stromal components found in SLOs including follicular dendritic cells, fibroblast reticular cells, lymphatic vessels, and high endothelial venules and possibly conduits are present in TLOs; their molecular regulation mimics that of LNs. Advances in visualization techniques and the development of transgenic mice that permit in vivo real time imaging of these structures will facilitate elucidation of their precise functions in the context of chronic inflammation. A clearer understanding of the inflammatory signals that drive non-lymphoid stromal cells to reorganize into TLO should allow the design of therapeutic interventions to impede the progression of autoimmune activity, or alternatively, to enhance anti-tumor responses.

MAIDS resistance-associated gene expression patterns in secondary lymphoid organs.

Murine acquired immunodeficiency syndrome (MAIDS) is caused by exposure to murine leukemia virus and serves as a model to study human AIDS. In MAIDS-susceptible C57BL/6 mice, virus exposure leads to progressive immune deficiency, while resistant strains such as BALB/c recover from infection and develop protective immunity. The goal of this study was to identify early gene expression patterns that may be important in establishing this strain-specific differential response. Total RNA was isolated from spleens and pooled lymph nodes of both mouse strains at 3 and 7 days post virus infection. The complementary DNA generated from this RNA was hybridized to mouse oligonucleotide DNA microarrays using a strategy that controlled for inherent variability and highlighted only virus-induced changes. Fluorescent intensities were normalized and analyzed for statistically significant differential expression between strains across both time points and lymphoid organs. The majority of the resistance-associated genes was identified at day 3 post-infection and demonstrated the highest fold differences between strains, while more susceptibility-associated sequences were seen at 7 days post-infection. Among the most highly differentially expressed sequences seen at the earlier time point were genes related to protein metabolism, especially serine proteases. Differential patterns of chemokine-related genes were observed at the later time point. The overall pattern of expression suggests strain-specific differences in proteases and chemokines within secondary lymphoid organs shortly after infection influence the likelihood of disease progression.

Retroviral transfer of donor MHC class I or MHC class II genes into recipient bone marrow cells can induce operational tolerance to alloantigens in vivo.

Infusion of allogeneic, donor bone marrow (BM) can induce specific immunological unresponsiveness in vivo resulting in long-term acceptance of subsequent fully allogeneic, donor-type solid organ grafts, but this may be associated with graft-versus-host disease. We hypothesize that transfer of donor MHC gene(s) to recipient-type BM or hematopoietic stem cells would enable delivery of donor alloantigens to the recipient without the risk of graft-versus-host disease. This strategy could also potentially take advantage of linked suppression to induce specific unresponsiveness to additional alloantigens expressed by the solid organ graft. We found that infusion of 5 x 10(6) CBA (H-2(k)) recipient mouse BM cells transduced with a recombinant replication-defective retrovirus encoding either a single donor MHC class I or class II gene (H-2K(b) or H-2IA(b)) in combination with anti-CD4 monoclonal antibody resulted in long-term survival of C57BL/10 (H-2(b)) but not third-party NZW (H-2(z)) heart grafts. BM cells (3 x 10(3)) enriched for hematopoietic stem cells by sorting for c-Kit(+), lineage-negative cells, were able to induce long-term allograft survival in 50% of recipients after transduction with the vector encoding a single donor MHC class I gene. These results have important implications for future strategies to enhance clinical allograft survival by delivery of donor alloantigens.

Correlates of nontransmission in US women at high risk of human immunodeficiency virus type 1 infection through sexual exposure.

Seventeen women who were persistently uninfected by human immunodeficiency virus type 1 (HIV-1), despite repeated sexual exposure, and 12 of their HIV-positive male partners were studied for antiviral correlates of non-transmission. Thirteen women had > or = 1 immune response in the form of CD8 cell noncytotoxic HIV-1 suppressive activity, proliferative CD4 cell response to HIV antigens, CD8 cell production of macrophage inflammatory protein-1 beta, or ELISPOT assay for HIV-1-specific interferon-gamma secretion. The male HIV-positive partners without AIDS had extremely high CD8 cell counts. All 8 male partners evaluated showed CD8 cell-related cytotoxic HIV suppressive activity. Reduced CD4 cell susceptibility to infection, neutralizing antibody, single-cell cytokine production, and local antibody in the women played no apparent protective role. These observations suggest that the primary protective factor is CD8 cell activity in both the HIV-positive donor and the HIV-negative partner. These findings have substantial implications for vaccine development.