Distributed Adaptive Search in T Cells: Lessons From Ants

Abstract

There are striking similarities between the strategies ant colonies use to forage for food and immune systems use to search for pathogens. Searchers (ants and cells) use the appropriate combination of random and directed motion, direct and indirect agent-agent interactions, and traversal of physical structures to solve search problems in a variety of environments. An effective immune response requires immune cells to search efficiently and effectively for diverse types of pathogens in different tissues and organs, just as different species of ants have evolved diverse search strategies to forage effectively for a variety of resources in a variety of habitats. Successful T cell search is required to initiate the adaptive immune response in lymph nodes and to eradicate pathogens at sites of infection in peripheral tissue. Ant search strategies suggest novel predictions about T cell search. In both systems, the distribution of targets in time and space determines the most effective search strategy. We hypothesize that the ability of searchers to sense and adapt to dynamic targets and environmental conditions enhances search effectiveness through adjustments to movement and communication patterns. We also suggest that random motion is a more important component of search strategies than is generally recognized. The behavior we observe in ants reveals general design principles and constraints that govern distributed adaptive search in a wide variety of complex systems, particularly the immune system.

Spatially distributed infection increases viral load in a computational model of SARS-CoV-2 lung infection

“…SIMCoV platform could be used to simulate other spatial interactions such as predator prey dynamics between immune and infected cells or collective action dynamics (11), like the collective search strategies of T cells (54).…”

Quorum sensing via dynamic cytokine signaling comprehensively explains divergent patterns of effector choice among helper T cells

“…It is possible that natural selection has converged on swarming as a common solution to such problems of uncertainty, both among individual organisms in groups as well as among individual cells within organisms. If the evolution of the mammalian immune system can be understood in this way, then more insights into its organization and functioning may emerge as analogies with other biological swarms are explored further [8,9].…”

“…Just as in insect swarms, this communication involves complex feedbacks within and among Th cells [12,13], which vary drastically in their signaling outputs [14,15,16,17]. Thus, we propose that the lens of collective behavior may reveal novel insights into how the immune system processes uncertain, conflicting, and changing information [8,9].…”

“…In particular, the mammalian immune system embodies many aspects of collective behavior. Immune cells are decentralized and autonomous individuals that together make coherent decisions despite substantial uncertainty [8,9]. For example, CD4+ helper T (Th) cells collectively decide whether a foreign invader warrants an immune response, and which immune effectors to deploy.…”

Migration of Cytotoxic T Lymphocytes in 3D Collagen Matrices

“…Thus, the ability of CTLs to efficiently navigate and search is crucial for an efficient immune response. Migration behavior of immune cells in the body and the search strategies they might follow is currently of great interest in physics and biology [5][6][7]. Migration of naive T cells in lymph nodes reportedly follows a Brownian or even subdiffusive dynamics [8][9][10], but switchings between fast and slow motility modes have also been observed [11].…”