Antigen-based immunotherapy (AIT) for autoimmune and allergic disease

Autoimmune and allergic diseases are major causes of morbidity. Antigen-based immunotherapy (AIT) is immunologically the most satisfying means of specifically targeting only those T cells driving disease, thereby inducing antigen-specific immune tolerance, with the lowest adverse risk profile. AIT is highly effective in rodent models of T cell-driven inflammation and is now in clinical trials. The range of approaches to applying AIT in the clinic prevents a consensus on the molecular basis for this form of tolerance. In particular, there has been a paucity of information on how pre-activated effector and memory T cells respond to AIT. New, advanced murine models of AIT are beginning to deliver such information at the cellular, biochemical, transcriptional and epigenetic levels

Immune mechanisms of protection: can adjuvants rise to the challenge?

For many diseases vaccines are lacking or only partly effective. Research on protective immunity and adjuvants that generate vigorous immune responses may help generate effective vaccines against such pathogens

Altered Chromosomal Positioning, Compaction, and Gene Expression with a Lamin A/C Gene Mutation

Lamins A and C, encoded by the LMNA gene, are filamentous proteins that form the core scaffold of the nuclear lamina. Dominant LMNA gene mutations cause multiple human diseases including cardiac and skeletal myopathies. The nuclear lamina is thought to regulate gene expression by its direct interaction with chromatin. LMNA gene mutations may mediate disease by disrupting normal gene expression.To investigate the hypothesis that mutant lamin A/C changes the lamina's ability to interact with chromatin, we studied gene misexpression resulting from the cardiomyopathic LMNA E161K mutation and correlated this with changes in chromosome positioning. We identified clusters of misexpressed genes and examined the nuclear positioning of two such genomic clusters, each harboring genes relevant to striated muscle disease including LMO7 and MBNL2. Both gene clusters were found to be more centrally positioned in LMNA-mutant nuclei. Additionally, these loci were less compacted. In LMNA mutant heart and fibroblasts, we found that chromosome 13 had a disproportionately high fraction of misexpressed genes. Using three-dimensional fluorescence in situ hybridization we found that the entire territory of chromosome 13 was displaced towards the center of the nucleus in LMNA mutant fibroblasts. Additional cardiomyopathic LMNA gene mutations were also shown to have abnormal positioning of chromosome 13, although in the opposite direction.These data support a model in which LMNA mutations perturb the intranuclear positioning and compaction of chromosomal domains and provide a mechanism by which gene expression may be altered

Co-IMMUNICATE: A project communicating immunity to the community

What is the Co-IMMUNICATE project? We are a group of researchers and teachers in Glasgow working together to help our local communities understand more about respiratory viruses and how our immune cells defend us against them. Each spring we work with the P6/7 class at Anderston primary school in Glasgow to design new activities that help enthuse and explain what happens when people are infected with a respiratory virus. Our project 2020 was the first year of the project and focused on describing what viruses are and what happens when we get infected. We ran various activities include “making your own snot” and “flu whispers” aimed to increase the pupil’s knowledge on how flu spreads; the immune response against it; and how viruses change when they pass between different people. In 2021, we decided to run an online compacted version of the project to ensure the delivery was feasible due to COVID-19. The theme was communication between cells infected with a virus and immune cells. Each session had a short display of information via slides before fun interactive activities involving skittles and cuddly microbes aimed to help the pupils understand various steps involved in the immune response. Our App The co-IMMUNICATE App was planned as another fun and informative tool that uses a tablet to help the pupils and the broader community understand what happens after a respiratory virus infection. The app is designed by our collaborators at the Glasgow school of Art with illustrations and voice overs done by the Anderton primary pupils. This app has been fundamental in us engaging with the public at events including the Glasgow science festival. The future In 2023, we aim shift focus and ask the pupils themselves to design their own activities to help younger children understand more about viruses. These displays will also be presented at the Glasgow Science festival allowing the pupils the opportunity to directly engage with the community