How a well-adapted immune system is organized

Abstract

SignificanceThe adaptive immune system uses the experience of past infections to prepare its limited repertoire of specialized receptors to protect organisms from future threats. What is the best way of doing this? Building a theoretical framework from first principles, we predict the composition of receptor repertoires that are optimally adapted to minimize the cost of infections from a given pathogenic environment. A naive repertoire can reach these optima through a biologically plausible competitive mechanism. Our findings explain how limited populations of immune receptors can self-organize to provide effective immunity against highly diverse pathogens. Our results also inform the design and interpretation of experiments surveying immune repertoires.

Diversity of immune strategies explained by adaptation to pathogen statistics

“…S1). As one may expect, the statistical properties of the protection tend to track the pathogen statistics (18). The more frequent the pathogen is, the more prevalent the protection in the population (Fig.…”

The evolution within us

“…It is also enhanced by many generations of natural selection on naive B-cell repertoires. Naive B cells, which have not encountered antigen, show extensive diversity arising from several sources: polymorphism in the receptor-coding genes, recombination between these genes, insertions and deletions [52,53]. The receptor genes themselves show selection for mutational hotspots and coldspots in structurally beneficial areas [54,55].…”

The Case for Absolute Ligand Discrimination: Modeling Information Processing and Decision by Immune T Cells

“…This issue of signalling pleiotropy is potentially a very generic problem in biology and we will coin the term "absolute discrimination" to describe it. Multitudes of receptors are indeed shared in examples as different as BMP signalling, olfaction, endocrine signalling, etc... More theoretical works have suggested that organization of immune repertoire requires strong overlapping signals [46,50]. In the context of this review, absolute discrimination thus is the specific and sensitive recognition of foreign ligands, independent of ligand quantity.…”

“…A simplified probabilistic model of T-cell activation has been derived using extreme values theories (modelling binding energy of TCRs to single ligand), from which probability of false positive can be computed [7], and collective decision was shown to improve with the help of cell to cell communications. Mayer et al very recently proposed a general framework, predicting that more receptors are needed for rate antigens, and strong cross-reactivity to correctly cover the full antigen landscape [46]. The future will certainly involve more statistical-physics based approaches that tackle the large number of lymphocytes and focus on such emergent properties.…”