How a well-adapting immune system remembers

Significance The adaptive immune system is able to protect us from a large variety of pathogens, even ones it has not seen yet. Can predicting the future pathogen distribution help in protection? We find that a combination of probabilistic forecasting and occasional sampling of the current environment reduces infection costs—a scheme easily implemented by the memory repertoire. The proposed theoretical framework offers a modular recipe for updating the memory repertoire, which quantitatively predicts the strength of the immune response in flu-vaccination experiments, unlike other update schemes. It also links the observed early life dynamics of the memory pool to the sparseness properties of the pathogen distribution and competitive receptor dynamics for pathogens.
An adaptive agent predicting the future state of an environment must weigh trust in new observations against prior experiences. In this light, we propose a view of the adaptive immune system as a dynamic Bayesian machinery that updates its memory repertoire by balancing evidence from new pathogen encounters against past experience of infection to predict and prepare for future threats. This framework links the observed initial rapid increase of the memory pool early in life followed by a midlife plateau to the ease of learning salient features of sparse environments. We also derive a modulated memory pool update rule in agreement with current vaccine-response experiments. Our results suggest that pathogenic environments are sparse and that memory repertoires significantly decrease infection costs, even with moderate sampling. The predicted optimal update scheme maps onto commonly considered competitive dynamics for antigen receptors.