Bulletin of the American Physical Society
APS March Meeting 2023
Volume 68, Number 3
Las Vegas, Nevada (March 5-10)
Virtual (March 20-22); Time Zone: Pacific Time
Session K68: Physics of Immune SystemsInvited
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Sponsoring Units: GMED Chair: Robert H. Austin Room: Room 420 |
Tuesday, March 7, 2023 3:00PM - 3:36PM |
K68.00001: Adaptation of CRISPR repertoires to the virome Invited Speaker: Vijay Balasubramanian Recent theoretical work suggests that the structure and organization of the immune repertoires of prokaryotes are shaped by adaptation to the statistics of viral infections. We explain these findings and their implications for the principles underlying CRISPR-based adaptive immunity. We discuss how more comprehensive sampling of natural viral diversity both across ecosystems, and across time, will inform these theories and our understanding of immunity against phage. Underlying this perspective is an analogy to the theory of sensory systems in neuroscience where adaptation to the statistics of the natural world has provided a powerful explanatory paradigm. |
Tuesday, March 7, 2023 3:36PM - 4:12PM |
K68.00002: Spatiotemporal Dynamics of Immune Cells in the Spinal Cord During CNS Autoimmunity Invited Speaker: Shivashankar Othy Our immune system is a dynamic network of cells and molecules that constantly protects us from pathogens. During an immune response, information about the pathogen is quickly relayed to the nearest lymphoid organs. Fast-moving immune cells (lymphocytes) constantly scan lymphoid organs for specific signals displayed on antigen-presenting cells (APC). Once lymphocytes encounter their antigens, they proliferate, differentiate into effector cells, and migrate to target tissues to execute effector functions (e.g., clear pathogens). These steps involve complex cell migration, cell-cell interactions, and signaling events that are exquisitely regulated to ensure targeted clearance of pathogens while limiting fatal autoimmunity. Misfiring immune cells against self-tissues can lead to more than 80 autoimmune disorders, including Multiple Sclerosis (MS), in which immune cells attack the protective myelin sheath of the neurons in the central nervous system (CNS). We aim to understand better how immune cells couple cell migration to functions in target tissues. |
Tuesday, March 7, 2023 4:12PM - 4:48PM |
K68.00003: Building models of T cells' self/non-self discrimination from automatized/dynamic high-dimensional experimental profiling Invited Speaker: Gregoire Altan-Bonnet We present an experimental/theoretical pipeline to build a quantitative model of antigen discrimination by T cells. We introduce a robotic platform to quantify the dynamics of cell differentiation and cytokine production/consumption by T cells ex vivo. These high-dimensional dynamics can be compressed into a 2D model using tools from machine learning. Our model highlights two modalities of T cell activation that enforce adaptive kinetic proofreading of antigen-TCR interactions, and that encode antigen discrimination. We test our model of antigen discrimination across varied immunological settings, including CAR-T and TCR-deficient T cells. To conclude, we highlight the power of lab automation, data integration, machine learning and theoretical modeling to usher new insights in systems immunology. |
Tuesday, March 7, 2023 4:48PM - 5:24PM |
K68.00004: Beyond density: Spatial distribution of lymphocytes in triple-negative breast cancer tumors Invited Speaker: Juliana Wortman The goal of immunotherapy is to mobilize the immune system to kill cancer cells. For solid tumors, immunotherapy is more effective if there is a high density of immune cells in the tumor. In fact, even without immunotherapy, the prognosis is better if a high density of immune cells known as lymphocytes are in the tumor. Lymphocytes consist of T and B cells. Killer T cells can destroy cancer cells and infected cells. B cells are best known for making antibodies. We consider triple negative breast cancer (TNBC) which is a particularly aggressive form of breast cancer. While the density of tumor-infiltrating T cells is now widely accepted to predict TNBC outcomes, the clinical significance of intratumoral B cell density is less clear. We have developed a number of techniques to quantify the spatial distribution of tumor-infiltrating T and B cells in TNBC, including box-counting, fractal dimension, and maximum-entropy methods. These methods allow us to measure the clustering or dispersion of lymphocytes on a wide range of spatial scales while being able to control for differences in overall density. Our results indicate that B cells in good-outcome tumors are more spatially dispersed, while B cells in poor-outcome tumors are more confined, independent of their average density. |
Tuesday, March 7, 2023 5:24PM - 6:00PM |
K68.00005: Models of ligand discrimination in cross-wired signaling pathways Invited Speaker: Anton Zilman Cellular signaling pathways exhibit remarkable specificity, discrimination and sensitivity. Puzzlingly, many signaling pathways common to the immune system are highly cross-wired whereby extracellular ligand molecules act through shared receptors or overlapping pathways downstream. It remains unclear how cells can reliably transmit information in such conditions especially when the ligands are present in multiple combinations. I will present several theoretical models of accurate and specific input-output mapping in cross-wired pathways, and show how a ligand-receptor signaling pathway can be mapped onto a classifier of an artificial neural network type. I will present the results of the combined experimental and computational testing of some of the theoretical models on the example of a major class of signaling molecules of the immune system, Type I Interferons (IFN), where multiple IFNs act through the same receptor. These results have important implications for the signaling by a broad class of cross-wired signaling pathways and for the clinical use of signaling molecules in disease treatment. |
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