Simpsonheide3072

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.In this study we developed a liposome-based vaccine containing palmitoylated synthetic long peptides (SLP) and alpha galactosylceramide (αGC) to specifically target dendritic cells (DC) for activation of both innate (invariant natural killer T-cells [iNKT]) and adaptive (CD8+ T-cells) players of the immune system. Combination of model tumor specific antigens (gp100/MART-1) formulated as a SLP and αGC in one liposome results in strong activation of CD8+ and iNKT, as measured by IFNγ secretion. Moreover, addition of lipo-Lewis Y (LeY) to the liposomes for C-type lectin targeting increased not only uptake by monocyte-derived dendritic cells (moDC), dermal dendritic cells and Langerhans cells but also enhanced gp100-specific CD8+ T- and iNKT cell activation by human skin-emigrated antigen presenting cells in an ex vivo explant model. Loading of moDC with liposomes containing LeY also showed priming of MART-126-35L specific CD8+ T-cells. In conclusion, chemically linking a lipid tail to a glycan-based targeting moiety and SLP combined with αGC in one liposome allows for easy generation of vaccine formulations that target multiple skin DC subsets and induce tumor antigen specific CD8+ T- and iNKT cells. These liposomes present a new vaccination strategy against tumors.Protective immunity to Mycobacterium tuberculosis (Mtb)-the causative agent of tuberculosis (TB)-is not fully understood but involves immune responses within the pulmonary airways which can lead to exacerbated inflammation and immune pathology. In humans, this inflammation results in lung damage; the extent of which depends on specific host pro-inflammatory processes. Neutrophils, though increasingly linked to the development of inflammatory disorders, have been less well studied in relation to TB-induced lung pathology. Neutrophils mode of action and their specialized functions can be directly linked to TB-specific lung tissue damage observed on patient chest X-rays at diagnosis and contribute to long-term pulmonary sequelae. This review discusses aspects of neutrophil activity associated with active TB, including the resulting inflammation and pulmonary impairment. It highlights the significance of neutrophil function on TB disease outcome and underlines the necessity of monitoring neutrophil function for better assessment of the immune response and severity of lung pathology associated with TB. Finally, we propose that some MMPs, ROS, MPO, S100A8/A9 and Glutathione are neutrophil-related inflammatory mediators with promising potential as targets for developing host-directed therapies for TB.Cord blood platelet rich plasma (CB-PRP) derivatives have been investigated as potential therapeutic agents for the treatment of diverse conditions including ocular surface disease and skin ulcers. We have developed processes for the formulation of several CB-PRP preparations, which have different composition and attributes. MK-0859 molecular weight Here we describe the molecular characteristics of these preparations and we make recommendations as to their most appropriate clinical application based on functional and immunomodulatory profiles. We show that incubation of adult peripheral blood mononuclear cells (PBMCs) with all three preparations dramatically reduced the production of INFγ and the expression of NKG2D and CD107a in NK, NKT, and T cells thus diminishing their activation, we propose that the likely mechanism is the high levels of soluble NKG2D ligands present in plasma. Of the three preparations we investigated, CB platelet lysate (PL) and platelet releaseate (PR) have higher concentrations of trophic and pro-angiogenic factors, CB platelet poor plasma (PPP) has the lowest concentration of all analytes measured. Based on these finding we propose that CB-PR is the most suitable raw material for skin wound patches, while CB-PL and PPP can be used to prepare eye drops for severe ocular surface pathologies and inflammatory conditions such as corneal ulcers or severe dry eye disease, respectively.Hemocytes play unequivocally central roles in host immune defense of bivalve mollusks, though the exact mechanisms underlying their functional differentiation are only partially understood. To this end, granulocytes and hyalinocytes were sorted via flow cytometry from hemocytes of the Pacific oyster Crassostrea gigas, and consequently quantitative transcriptomic analysis revealed a striking array of differentially expressed genes (DEGs), which were globally upregulated in granulocytes, dedicating to functional differentiation among oyster hemocytes. Our network of DEGs illustrated actively engaged signaling pathways, with Cdc42/Cdc42l being a core regulator of pathway network, which was validated by a dramatically reduced capacity for hemocyte phagocytosis in the presence of Cdc42 inhibitors. Additionally, a number of transcription factors were identified among DEGs, including ELK, HELT, and Fos, which were predominantly expressed in granulocytes. The AP-1 transcription factor Fos was confirmed to facilitate functional differentiation of hemocytes in an assay on binding to target genes by the AP-1 binding site, consistent with downstream phagocytosis and ROS production. Importantly, Cdc42/Cdc42l were also regulated by the expression of Fos, providing a possible regulatory mechanism-guided hemocyte functional differentiation. Findings in this study have bridged a knowledge gap on the mechanistic underpinnings of functional differentiation of hemocytes in a marine invertebrate C. gigas, which promise to facilitate research on the evolution of immune defense and functional differentiation of phagocyte in higher-order and more recent phyla.Pancreatic adenocarcinoma (PDAC) is a highly fatal disease worldwide. MicroRNAs (miRNAs) could regulate the protein-coding RNAs related to tumor growth, invasion, and immune evasion. Therefore, the investigation of novel miRNAs may be helpful in the development of more effective therapies for PDAC. In this study, we investigated the role and mechanism of action of miR-128 in PDAC. By using bioinformatics methods, we found that decreased expression of miR-128 was associated with poor overall survival of PDAC. miR-128 was inversely correlated with cluster of differentiation 47 (CD47), which was positively related to zinc finger E-box-binding homeobox 1 (ZEB1) in PDAC. Through in vivo experiments, we found that miR-128 could suppress the growth and metastasis of PDAC. Analysis of the immune microenvironment demonstrated that overexpression of miR-128 on tumor cells could increase the percentages of dendritic cells (DCs), CD8+ T lymphocytes, and natural killer T cells (NKT) in the tumor and spleen, consequently enhancing anti-tumor immunity. In vitro assays showed that miR-128 could inhibit cell proliferation, clonogenicity, migration, and invasion in Panc02 cells and could also enhance the phagocytosis of macrophages and the activity of DCs. link2 Western blot and qRT-PCR confirmed that miR-128 could regulate ZEB1 and further inhibit CD47 in pancreatic cancer cells. Therefore, we identified a novel regulatory anti-tumor mechanism by miR-128 in PDAC, which may serve as a novel therapy for PDAC.Previous studies showed that monoclonal immunoglobulins G (IgGs) of "monoclonal gammopathy of undetermined significance" (MGUS) and myeloma were hyposialylated, thus presumably pro-inflammatory, and for about half of patients, the target of the monoclonal IgG was either a virus-Epstein-Barr virus (EBV), other herpes viruses, hepatitis C virus (HCV)-or a glucolipid, lysoglucosylceramide (LGL1), suggesting antigen-driven disease in these patients. In the present study, we show that monoclonal IgAs share these characteristics. We collected 35 sera of patients with a monoclonal IgA (6 MGUS, 29 myeloma), and we were able to purify 25 of the 35 monoclonal IgAs (6 MGUS, 19 myeloma). link3 Monoclonal IgAs from MGUS and myeloma patients were significantly less sialylated than IgAs from healthy volunteers. When purified monoclonal IgAs were tested against infectious pathogens and LGL1, five myeloma patients had a monoclonal IgA that specifically recognized viral proteins the core protein of HCV in one case, EBV nuclear antigen 1 (EBNA-1) in four cases (21.1% of IgA myeloma). Monoclonal IgAs from three myeloma patients reacted against LGL1. In summary, monoclonal IgAs are hyposialylated and as described for IgG myeloma, significant subsets (8/19, or 42%) of patients with IgA myeloma may have viral or self (LGL1) antigen-driven disease.Woodchuck infected with woodchuck hepatitis virus (WHV) represents the pathogenically nearest model of hepatitis B and associated hepatocellular carcinoma (HCC). This naturally occurring animal model also is highly valuable for development and preclinical evaluation of new anti-HBV agents and immunotherapies against chronic hepatitis (CH) B and HCC. Studies in this system uncovered a number of molecular and immunological processes which contribute or likely contribute to the immunopathogenesis of liver disease and modulation of the systemic and intrahepatic innate and adaptive immune responses during hepadnaviral infection. Among them, inhibition of presentation of the class I major histocompatibility complex on chronically infected hepatocytes and a role of WHV envelope proteins in this process, as well as augmented hepatocyte cytotoxicity mediated by constitutively expressed components of CD95 (Fas) ligand- and perforin-dependent pathways, capable of eliminating cells brought to contact with hepatocyte surfl which affect effectiveness of the anti-viral systemic and intrahepatic immune responses, and modify liver disease outcomes. Further exploration of these and other mechanisms, either already discovered or yet unknown, and their interactions should bring more comprehensive understanding of HBV pathogenesis and help to identify novel targets for therapeutic and preventive interventions. The woodchuck model is uniquely positioned to further contribute to these advances.