Computer Science ETDs

Publication Date

Summer 7-29-2025

Abstract

The adaptive immune response is a complex defense mechanism that develops over time to recognize and eliminate pathogens with remarkable precision and durability. This dissertation investigates the dynamics, scaling, and efficiency of the adaptive immune response through a synthesis of computational modeling, mathematical analysis, and agent-based simulations. First, we analyze the topology of the lymphatic network and investigate the T cell search time to find the lymph node that is containing the matching dendritic cell. Second we show how the scaling of lymph node number and volume with body mass, leads to scale-invariant search times for T cells locating antigen-bearing dendritic cells across species. Third, we develop an analytical and numerical framework for extreme first passage time (EFPT) in confined three-dimensional volumes, revealing a transition from inverse-linear to inverse-logarithmic scaling of the fastest searcher’s discovery time as the number of searchers increases. This framework is validated against large-scale Monte Carlo simulations modeling T cells searching for a central target. Finally, we construct an agent-based model of B cell–mediated immunity to examine affinity maturation, antigenic drift, and vaccine efficacy against rapidly mutating viral variants. By representing receptors and epitopes in shape space and simulating somatic hypermutation and clonal selection, our model predicts population dynamics of B cells, antibodies, and antigens over repeated exposures. Together, these studies elucidate fundamental principles of immune surveillance and response timing, with implications for translational vaccine design and broader applications in search theory, chemical kinetics, and complex systems.

Language

English

Keywords

Immune System, Lymph Node, Lymphatic Network, Extreme First Passage TIme, Repeated Vaccine Efficacy, SARS-CoV2

Document Type

Dissertation

Degree Name

Computer Science

Level of Degree

Doctoral

Department Name

Department of Computer Science

First Committee Member (Chair)

Melanie Moses

Second Committee Member

Bruna Jacobson

Third Committee Member

G. Matthew Fricke

Fourth Committee Member

Mousumi Roy

Project Sponsors

NSF Award 2030037 & 2020247

Download

Share

COinS