Generation of immune responses within lymph nodes during type-I inflammation

Abstract

Immune responses must be rapid, tightly orchestrated, and tailored to the encountered stimulus. Lymphatic vessels facilitate this process by continuously collecting immunological information (i.e., antigens, immune cells, and soluble mediators) about the current state of peripheral tissues, and transporting these via the lymph across the lymphatic system. Lymph nodes (LNs), which are critical meeting points for innate and adaptive immune cells, are strategically located along the lymphatic network to intercept this information. Within LNs, immune cells are spatially organized, allowing them to efficiently respond to information delivered by the lymph, and to either promote immune homeostasis or mount protective immune responses. These responses involve the activation and functional cooperation of multiple distinct cell types, and are tailored to the specific inflammatory conditions. The natural patterns of lymph flow can also generate spatial gradients of antigens and agonists within draining LNs, which can in turn further regulate innate cell function and localization, as well as the downstream generation of adaptive immunity. In this dissertation, we explore how information transmitted by the lymph shapes the spatiotemporal organization of innate and adaptive immune responses in LNs, with particular focus on type-I inflammation.