Cold Spring Harbor Conference on Systems Immunology Cold Spring Harbor, NY April 20 – 24, 2021 ABSTRACT Immune responses are orchestrated by diverse cells and molecules operating over space and time and across different scales, for example, extremely complex repertoires of lymphocyte receptors can discriminate between self and non-self antigens and subsequently trigger dynamic cell-cell interactions culminating in the production of effector functions including antibodies and killing of virus infected cells. Critical discoveries have been made by experimental immunologists studying individual molecules, cells, and their interactions. Due to the complexity of the interactions among these diverse immune components, many fundamental issues associated with immune regulation and response orchestration remain unresolved. Further progress requires an integration of high-dimensional multi-omic approaches, and computational and quantitative modeling to analyze cellular behaviors at various scales of the system. These properties cannot be analyzed or intuited by conventional experiments. It is clear that effective collaborations between experimental immunologists and computational and systems biologists are required to advance our systems-level understanding of immune responses. This meeting is the second in a biennial series that will nurture a cross-disciplinary exchange of new ideas and technologies in the rapidly evolving and expanding field of systems immunology. Building on the success of the initial meeting held at CSHL in 2019, we hope to establish this recurring meeting as the leading forum that will sustain a highly interactive community of Systems Immunologists. The proposed meeting will focus on recent advances at the interface of immunology and systems and computational biology, including rational design and applications of engineered immune particles and cells. Sessions will highlight multi-dimensional experimental platforms and computational approaches that are being used to analyze signaling and genomic states of individual immune cells that control discrete effector responses in a spatiotemporal manner. Integration of immunogenic, tolerogenic or pathophysiologic responses at different levels of scale – cellular, tissues and organs in mice and humans will be explored. Shared and unique design principles that underlie the development, functioning and evolution of the immune system will be discussed from an analytic standpoint. Given the COVID-19 pandemic, a new session will be devoted to the high-dimensional analyses of immune responses to SARS-CoV-2 infection as well as to vaccines that are currently undergoing clinical development. The meeting will nurture and foster a community of systems immunologists that are coupling high-dimensional profiling and imaging with computational and quantitative analyses to deepen the understanding of immune system states and responses. Oral presentations will be given by a group of distinguished invited ...