Roles of repertoire diversity in robustness of humoral immune response

TL;DR

This paper presents a minimal mathematical model demonstrating how reduced antibody repertoire diversity and increased self-reactivity with age can impair the speed and effectiveness of the humoral immune response.

Contribution

It introduces a novel minimal model linking repertoire diversity and self-reactivity to immune response efficiency, especially in aging.

Findings

Reduced repertoire diversity slows immune response.

Increased self-reactivity impairs pathogen neutralization.

Model predicts slower immune responses in aged immune systems.

Abstract

The adaptive immune system relies on diversity of its repertoire of receptors to protect the organism from a great variety of pathogens. Since the initial repertoire is the result of random gene rearrangement, binding of receptors is not limited to pathogen-associated antigens but also includes self antigens. There is a fine balance between having a diverse repertoire, protecting from many different pathogens, and yet reducing its self-reactivity as far as possible to avoid damage to self. In the ageing immune system this balance is altered, manifesting in reduced specificity of response to pathogens or vaccination on a background of higher self-reactivity. To answer the question whether age-related changes of repertoire in the diversity and self/non-self affinity balance of antibodies could explain the reduced efficacy of the humoral response in older people, we construct a minimal mathematical model of the humoral immune response. The principle of least damage allows us, for a given repertoire of antibodies, to resolve a tension between the necessity to neutralise target antigens as quickly as possible and the requirement to limit the damage to self antigens leading to an optimal dynamics of immune response. The model predicts slowing down of immune response for repertoires with reduced diversity and increased self-reactivity.