CD154 is necessary for mice to clear a Cryptosporidium parvum infection, but whether this ligand has to be expressed on T cells with specificity for C. parvum has not been determined. We infected DO11.10 (ovalbumin specific) T-cell receptor transgenic mice that had been bred to a RAG ؊/؊ background with C. parvum and found that the infection was cleared within 6 weeks, while RAG ؊/؊ controls were unable to clear C. parvum infection. Recovery was accompanied by an increase in the number of splenic T cells with the CD44 high phenotype that characterizes memory cells. To determine whether a C. parvum-infected environment sufficed to activate transgenic T cells, we reconstituted C. parvum-infected BALB/c SCID mice with DO11.10 RAG ؊/؊ splenocytes. Fecal excretion of C. parvum antigen ceased in the 12 weeks following the adoptive transfer, unless the mice were also injected with tolerizing doses of ovalbumin. DO11.10 T cells were found in the submucosa of C. parvum-infected, but not uninfected, BALB/c SCID hosts within 48 h of injection. The transferred DO11.10 T cells divided and acquired a CD44 high memory phenotype in C. parvum-infected, but not uninfected, recipients. DO11.10 splenocytes from CD154 knockout donors failed to clear a C. parvum infection, confirming a requirement for CD154 in recovery. In vitro, the DO11.10 cells did not proliferate in response to C. parvum antigen, and a tBlast GenBank search revealed no matches between the ovalbumin peptide and C. parvum DNA sequences. C. parvum-infected SCID mice given RAG ؊/؊ CD8 ؉ T cells with a Listeria-specific transgene did not recover from C. parvum infection. Our data suggest that antigen-nonspecific CD4 ؉ T-cell effector mechanisms in combination with the innate arm of the immune system are sufficient for the eradication of C. parvum infection.Cryptosporidium parvum causes severe diarrhea and weight loss in immunodeficient subjects, including those with AIDS (13) and boys with CD154 gene mutations causing X-linked immunodeficiency with hyper-immunoglobulin M (IgM) (17,20), but healthy adults have little if any symptomatology (9). T-cell-deficient mice fed C. parvum oocysts are infected first in the gut and some 6 weeks later in the intra-and extrahepatic biliary tree (29). Previous studies showed that C. parvum-infected SCID mice would clear the C. parvum infection if they were reconstituted with CD4 T cells (22,24) and that recovery was impaired by antibody to gamma interferon (IFN-␥) (7, 30), interleukin 4 (IL-4) (2), and IL-12 (31). Along with a requirement for major histocompatibility complex (MHC) class II expression (1), it seems likely that CD4 responses are central to recovery from C. parvum infection. Whether the CD4 response is contingent on stimulation of C. parvum-specific T cells by a C. parvum peptide on a class II molecule, or whether bystander T cells of other specificities might suffice to clear a C. parvum infection, is not known. Our own results indicate that a T-cell activation molecule, CD154, is necessary for C. parvum defense, becau...

Storytelling is a highly effective strategy for delivering course content. It can provide real-world contexts and the relevance students desire. Through personal connections to the narrative details, anecdotes facilitate the incorporation of content into pre-existing knowledge and neural networks that enhances retention. In addition, stories can honor students' diverse backgrounds, which builds a sense of belonging and community. In turn, these aspects can drive intrinsic motivation to learn and increase students' alertness in class and overall engagement in the course. Despite the educational power of stories, there often is not enough time to integrate them into curricula. To address this dilemma, faculty can condense stories into micro-stories that require relatively minimal class time. Many aspects of stories that enhance learning can be leveraged in just a few sentences by focusing on narrative details that engage a variety of cognitive and emotional processes. In particular, the inclusion of multiple sensory descriptions and small details, like locations and names, can provide sufficient context to maintain the value stories provide. Micro-stories can function independently or extend a single theme throughout a course. Presented in this Perspective are examples of micro-stories for concepts in immunology and strategies for developing them. Proposals are made for leveraging micro-stories to enhance student engagement and course community, content retention and retrieval, and satisfaction with immunology courses of all sizes and levels.

Thymocyte positive and negative selection are dependent on avidity-driven TCRmediated recognition events in the thymus. High-avidity recognition events result in negative selection, while low-avidity recognition events result in positive selection. However, it has not been established how thymocytes maturation stages affect their responses to TCR signals of different avidities. We gained insight into this question when we reduced thymocyte selection to an in vitro system, in which full maturation of developmentally synchronized immature double-positive thymocytes was induced on a cloned line of thymic epithelial cells. Our analysis of the kinetics of thymocyte development supports a multi-phasic model of thymic selection. In it, thymocyte maturation stages as well as interaction avidity control the outcome TCR stimulation. Positive selection is initiated during a primary recognition event that proceeds independently of the TCR avidity. During a secondary recognition event the final fate of thymocyte, full maturation versus negative selection, is determined by TCR avidity.

When done purposely, case studies blend desires of modern students for relevance and social engagement with educators needs to convey detailed content and develop critical thinking skills. By selecting or creating cases that include both local and international settings as well as characters from broad socio-economic and cultural backgrounds, we elevate discussions of diversity and students’ feelings of inclusivity. In addition, even terse mini-scenarios can require students to analyze situations and apply their knowledge instead of memorize facts. For many, finding or writing exciting narratives and integrating case study strategies can seem daunting. However, barriers to adopting this pedagogical tool are reduced when educators recognize that cases are 1) highly variable in depth (from a few sentences to several pages), and 2) can be used very flexibly. Here, we explain examples of how we have integrated cases of various lengths throughout an undergraduate immunology course. Two examples of how a single, well selected case can address topics through an entire term will be detailed. We will explain a simple strategy for converting standard exam or practice questions into mini-cases, leveraging summaries of primary literature and the course text. All classroom ready resources will be available for immediate access through AAI’s preferred method.