Bulletin of the American Physical Society
APS March Meeting 2020
Volume 65, Number 1
Monday–Friday, March 2–6, 2020; Denver, Colorado
Session P26: Immune Sensing and ResponseFocus
|
Hide Abstracts |
Sponsoring Units: DBIO DCP Chair: Ned Wingreen, Princeton University Room: 403 |
Wednesday, March 4, 2020 2:30PM - 3:06PM |
P26.00001: Universality of biochemical feedback and its application to immune cells Invited Speaker: Amir Erez Positive feedback is ubiquitous in biochemical networks and can lead to a bifurcation from a monostable to a bistable cellular state. One such example is the immune self/foreign decision, which is manifested in a complex biochemical cascade. We consider a coarse-grained view of this cascade, its output and response to inhibition, and propose a theory which maps the stochastic dynamics to thermodynamic state variables. Our mapping allows experimental data analysis without curve fitting and highlights previously unknown features in the data. Beyond steady state, our theory reveals critical slowing down and a universal scaling of the response to changing stimulus. Finally, motivated by the immunological synapse, where a pair of cells communicate with each other through molecule exchange, we consider a pair of sensing/responding cells and how they might communicate effectively. |
Wednesday, March 4, 2020 3:06PM - 3:18PM |
P26.00002: Optimal non-equilibrium decision making to store immune memory Oskar Schnaack, Armita Nourmohammad Our adaptive immune system consists of highly diverse immune receptors to mount specific responses against a multitude of pathogens. During an infection, a fraction of these receptors forms a memory for later encounters. Here, we address a key question: which of the immune receptors should be kept as memory so that they can mount a response against evolved forms of the original pathogen in future infections? To do so, we have developed a theoretical framework, where memory storage is a non-equilibrium decision-making process between an adaptive exploration to mount a specific response and exploitation of existing yet suboptimal memory that can be utilized immediately to suppress an infection. To achieve a long-term benefit for the host, we show that memory generation should involve feedback from receptors’ affinity and should favor cross-reactive receptors with a moderate affinity over high-affinity receptors against the infecting pathogen. The recipe for memory generation should be tuned over the host’s evolutionary timescale based on the pathogenic evolutionary rates. Our results are consistent with recent experiments that suggest cell fate decisions during memory generation are highly regulated to balance the affinity and cross-reactivity of immune receptors. |
Wednesday, March 4, 2020 3:18PM - 3:30PM |
P26.00003: Visualizing and controlling immune response to gut microbes Brandon Schlomann, Travis J Wiles, Elena S Wall, Karen Guillemin, Raghuveer Parthasarathy Trillions of bacteria reside in the intestine where they are largely kept away from epithelial surfaces. When this spatial confinement is broken, the resulting immune responses can be damaging and lead to disease. Understanding the processes that spatially restrict gut bacteria will open new avenues for microbiome-based therapies. I will present work that investigates interactions between immune cells and resident gut bacteria through live imaging of naturally transparent, larval zebrafish. We discovered that flagella-based swimming motility enables a native Vibrio species to govern its own spatial organization within the gut and stimulate a potent immune response. Mutants that cannot swim become aggregated and confined to the interior lumen of the gut. Loss of motility also leads to reduced expression of the proinflammatory cytokine TNFα in gut-associated macrophages and in the liver. Externally-inducible genetic switches enabled in situ manipulation of bacterial motility, and therefore external control of both bacterial spatial distribution and proinflammatory potential. Our findings reveal connections between the physical activity of bacteria, their spatial organization, and host inflammatory activity. |
Wednesday, March 4, 2020 3:30PM - 3:42PM |
P26.00004: Durable Control of Macrophage Polarizations with Backpacks Wyatt Shields, Michael Evans, Lily Wang, Samir Mitragotri Adoptive cell transfers have emerged as a disruptive approach to treat diseases in a manner that is more specific than using small molecule drugs. However, unlike traditional drugs, cells are living entities that can alter their function in response to subtle environmental cues. In this talk, I will present a class of particles, referred to as “backpacks”, that can regulate the phenotype of adoptively transferred macrophages in vivo. Backpacks are able to robustly adhere to macrophage surfaces and evade phagocytosis for several days. Once attached, backpacks can release encapsulated pro-inflammatory cytokines to potentiate antitumor (M1) phenotypes in macrophages, even in tumor-mimicking conditions. When injected intratumorally into mice bearing breast tumors, a potent immunosuppressive (M2) environment, backpacks allowed macrophages to maintain their M1 phenotypes. Conserved phenotypes led to significantly reduced metastatic burdens and slowed tumor growths compared to those of mice treated with an equal dose of free cytokine. Overall, controlled release of cytokines from backpacks may enable a new strategy to regulate phenotypes of adoptively transferred cells to aid in the treatment of a variety of inflammatory and autoimmune diseases. |
Wednesday, March 4, 2020 3:42PM - 3:54PM |
P26.00005: Inference and adaptation in innate immunity Yawei Qin, Emily Mace, John Barton Cells such as natural killer cells and macrophages can recognize and eliminate targets with aberrant surface ligand expression without antigen specificity. This innate mechanism of activation must be tightly regulated to prevent autoimmunity. We describe a quantitative model of the regulation of nonspecific activation that is grounded in Bayesian inference. Our model captures known behaviors of innate immune cells, including adaptation to changing environments and the development of hyposensitivity after prolonged exposure to activating signals. Our analysis reveals a tradeoff between precision and flexible adaptation to different environments. Maintaining the ability to adapt naturally leads to heterogeneous responses, even for hypothetical populations of immune cells and targets that have identical surface receptor and ligand expression. Collectively, our results describe an adaptive algorithm for self/nonself discrimination that functions even in the absence of antigen restriction and supports biological observations of single-cell heterogeneity in response to cell-cell interactions. The same model could also apply more broadly to the adaptive regulation of activation for other immune cell types. |
Wednesday, March 4, 2020 3:54PM - 4:06PM |
P26.00006: A mathematical model of aging in the immune system Eric Jones, Jiming Sheng, Shenshen Wang, Jean M Carlson The adaptive and innate branches of the vertebrate immune system work in close collaboration to protect organisms from harmful pathogens. As the organism ages the immune system undergoes immunosenescence, characterized by declined performance or malfunction in either branch, which can lead to various diseases and death. In this study we develop a mathematical model of the immune system that couples the innate and adaptive components of the immune system, allowing investigation of the mutual modulation of the innate and adaptive immune branches over time. Our results capture the clinically-observed chronic inflammatory response affiliated with aging (“inflamm-aging”), and find that the timing of this persistent inflammatory response is dependent on the history of pathogen encounters. By consolidating complex immune feedbacks into a mathematical model, our results inform the mechanisms responsible for immunosenescence and offer opportunities for their further exploration through quantitative modeling. |
Wednesday, March 4, 2020 4:06PM - 4:18PM |
P26.00007: B cells use mechanical energy to distinguish affinity and speed up adaptation Hongda Jiang, Shenshen Wang Generation of potent antibodies relies on positive selection of germinal center (GC) B cells expressing high affinity receptors. Effective selection during the rapid evolutionary process called affinity maturation requires efficient ranking of affinity. Yet, the mechanism by which affinity discrimination is achieved and how it affects B cell evolution remains unclear. Growing evidence shows that B cells use mechanical forces to actively extract antigens from the surface of antigen-presenting cells. Here we study the stochastic process of antigen extraction using theory and simulations. We find that application of mechanical force alters the energy landscape of molecular interactions and consequently extends the range of distinguishable affinities. Integrating this extraction model on the molecular scale with GC dynamics on the population level, we demonstrate that exertion of cytoskeletal forces for antigen extraction can accelerate the rate of affinity maturation. |
Wednesday, March 4, 2020 4:18PM - 4:30PM |
P26.00008: Aging in the immune system is a loss of balance Jiming Sheng, Eric Jones, Jean M Carlson, Shenshen Wang The innate and adaptive arms of the vertebrate immune system work in close collaboration to protect organisms from harmful pathogens. As an organism ages its immune system undergoes immunosenescence, characterized by degraded performance or malfunction, in either arm, that leads to diseases and even death. However, a system-level mechanism of immunosenescence is not understood. |
Wednesday, March 4, 2020 4:30PM - 4:42PM |
P26.00009: Influenza virus geometry shapes the immune response against it Assaf Amitai, Maya Sangesland, Daniel Lingwood, Arup K Chakraborty Influenza surface glycoprotein – Hemagglutinin (HA) is the main target of the immune system following exposure to the virus. Most antibodies elicited following vaccination or infection are created against the head, which is highly mutable. A vaccination approach that would target immune response towards evolutionarily conserved residues on hemagglutinin stem can elicit broadly neutralizing antibodies capable of fighting many flu strains. |
Wednesday, March 4, 2020 4:42PM - 4:54PM |
P26.00010: Spurious higher-order correlations from non-linearities in a receptor-ligand model Richard Zhu, Arvind Murugan Multi-body correlations arise frequently in analyses of biological systems, such as antibiotic interactions in cell growth rate, mutational interactions on protein function and ligand interactions in the immune system. In particular, it is common practice to measure the 1st and 2nd-moments of quantities of interest, and fit a maximum-entropy model to the data. We demonstrate that pairwise and higher-order interactions emerge naturally from mismatches between the fitted model and the underlying physical system, as well as ignorance of unmeasured quantities. We study a simple receptor-ligand model and demonstrate that spurious higher-order interactions can arise from simpler interactions combined with non-linearities not accounted for. Our analysis shows how careful accounting for the underlying biology is needed to conclude the existence or absence of complex interactions within the system. |
Wednesday, March 4, 2020 4:54PM - 5:30PM |
P26.00011: To die or not to die: Cell decision-making in the face of viral threat Invited Speaker: Jennifer Oyler-Yaniv Paradoxically, the pro-inflammatory cytokine Tumor Necrosis Factor α (TNFα) simultaneously activates opposing pro-apoptotic and pro-survival signaling. We show that the activation of antagonistic pathways changes the properties of cell fate decision transitioning cells from a “slow and accurate” to “fast and error-prone” decision mode. Mathematical modeling predicts, and experiments in vitro and in vivo validate, that the regulation of the decision mode of non-immune cells by innate immune cell production of TNFα is key to prevent viral spread. Overall our results demonstrate how a collective phenotype emerges from the regulation of fundamental tradeoffs within cellular cognitive processes. |
Follow Us |
Engage
Become an APS Member |
My APS
Renew Membership |
Information for |
About APSThe American Physical Society (APS) is a non-profit membership organization working to advance the knowledge of physics. |
© 2024 American Physical Society
| All rights reserved | Terms of Use
| Contact Us
Headquarters
1 Physics Ellipse, College Park, MD 20740-3844
(301) 209-3200
Editorial Office
100 Motor Pkwy, Suite 110, Hauppauge, NY 11788
(631) 591-4000
Office of Public Affairs
529 14th St NW, Suite 1050, Washington, D.C. 20045-2001
(202) 662-8700