K63 ubiquitination in immune signaling.

Ubc13-catalyzed K63 ubiquitination is a major control point for immune signaling. Recent evidence has shown that the control of multiple immune functions, including chronic inflammation, pathogen responses, lymphocyte activation, and regulatory signaling, is altered by K63 ubiquitination. In this review, we detail the novel cellular sensors that are dependent on K63 ubiquitination for their function in the immune signaling network. Many pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can target K63 ubiquitination to inhibit pathogen immune responses; we describe novel details of the pathways involved and summarize recent clinically relevant SARS-CoV-2-specific responses. We also discuss recent evidence that regulatory T cell (Treg) versus T helper (TH) 1 and TH17 cell subset regulation might involve K63 ubiquitination. Knowledge gaps that merit future investigation and clinically relevant pathways are also addressed.

Designing Cases for Case-Based Immunology Teaching in Large Medical School Classes.

Case-based, interactive sessions for small groups (in a large medical school class of 150 students) reinforces basic immunology concepts by including clinical scenarios that stimulate student learning and consolidate critical concepts. Careful design of cases (designing backwards from the key concepts) leads students through successively more complicated and linked group-work questions. This paper details why cases are effective learning tools, how to design an effective case, how to ask appropriate questions and how to help students apply basic immunology concepts to a case. Each group work session is facilitated and followed by a question and answer presentation by faculty, where student groups are directly asked to answer the questions and also challenged with "bonus questions" not presented with the original case. This allows students to "put together" immunology information into a "story" that they can tell and prevents student frustration by summarizing the results at the end of each case. Case design is carefully discussed including clinical relevancy and accuracy, how to write questions that do not give away the answers, how to emphasize mechanistic questions that allow students to "clinically explain as a physician" the immunological basis for the answers. Additionally, students better understand the role of immunity in both normal and disease states. A case-based approach promotes student learning by re-emphasizing basic concepts in the context of the case and promotes better students understanding of critical immunological concepts.

Role for toll-like receptor 4 in TNF-alpha secretion by murine macrophages in response to polysaccharide Krestin, a Trametes versicolor mushroom extract.

Woody fungi and yeast preparations show promise in cancer treatment by activating anti-tumor immune responses. Macrophages (J774A.1) were treated with PSK, Reishi extract, scleroglucan or vehicle control. Pre-incubation with TLR4 blocking antibody inhibited TNF-alpha secretion by both J774A.1 cells and primary splenocytes but had inconclusive effect on scleroglucan-induced secretion of TNF-alpha. PSK induced TNF-alpha and IL-6 secretion by wild type but not by TLR4-deficient peritoneal macrophages. We conclude that constituents from PSK act as ligands for TLR4 receptors leading to induction of TNF-alpha and IL-6 inflammatory cytokines. Receptor-mediated differences may be due to structural differences in beta glucans or non-glucan constituents.