Expanding the Immunological Toolkit for Modeling Adaptive Immunity, Predicting Immunotoxicology, and Staining of Lymphoid Tissues 5 views

The ability to faithfully recapitulate the cellular and chemical processes that occur within the lymph node is a grand challenge. Nevertheless, innovation must take place to better our understanding of the mechanisms that underly immunity. In doing so, there exists the potential to improve upon the safety and efficacy of therapeutics, as well as develop novel approaches to preventing the spread of diseases. In this regard, extensive effort has gone into developing models of the adaptive immune response. Traditional methods of study include the use of 2D cell cultures or animal models. However, as the field grows it becomes clear these approaches either lack in their ability to capture the intricate processes that underly humoral immunity, or are limited by the degree of control that can be imposed. To reduce the level of compromise needed between these two models, Chapter 2 focuses on the development of a lymph node microphysiological system (LN MPS). Within, we describe our approach to inducing polyclonal IgM secretion and plasmablast differentiation when starting solely with isolated naïve human T and B lymphocytes. Chapter 3 addresses the requirements to obtain spatial information within in vitro systems using a two-fold approach. In the first section we outline the creation of a novel tool for staining lymph node slices. While the second half aims to optimize conditions for non-specific labeling of naïve T cells. Chapter 4 expands upon the application space of the LN MPS for predicting drug-induced immunotoxicities. In summation, the work contained in this thesis describes advancements made to the researchers’ toolkit for modeling adaptive immunity.

PHD (Doctor of Philosophy)

Microphysiological Systems; Immunology; Lymph Node; Adaptive Immunity

English

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2026-07-31