An evolutionary perspective on the systems of adaptive immunity

Abstract

We propose an evolutionary perspective to classify and characterize the diverse systems of adaptive immunity that have been discovered across all major domains of life. We put forward a new function-based classification according to the way information is acquired by the immune systems: Darwinian immunity (currently known from, but not necessarily limited to, vertebrates) relies on the Darwinian process of clonal selection to 'learn' by cumulative trial-and-error feedback; Lamarckian immunity uses templated targeting (guided adaptation) to internalize heritable information on potential threats; finally, shotgun immunity operates through somatic mechanisms of variable targeting without feedback.We argue that the origin of Darwinian (but not Lamarckian or shotgun) immunity represents a radical innovation in the evolution of individuality and complexity, and propose to add it to the list of major evolutionary transitions. While transitions to higher-level units entail the suppression of selection at lower levels, Darwinian immunity re-opens cell-level selection within the multicellular organism, under the control of mechanisms that direct, rather than suppress, cell-level evolution for the benefit of the individual. From a conceptual point of view, the origin of Darwinian immunity can be regarded as the most radical transition in the history of life, in which evolution by natural selection has literally re-invented itself. Furthermore, the combination of clonal selection and somatic receptor diversity enabled a transition from limited to practically unlimited capacity to store information about the antigenic environment. The origin of Darwinian immunity therefore comprises both a transition in individuality and the emergence of a new information system -the two hallmarks of major evolutionary transitions.Finally, we present an evolutionary scenario for the origin of Darwinian immunity in vertebrates. We propose a revival of the concept of the 'Big Bang' of vertebrate immunity, arguing that its origin involved a 'difficult' (i.e. low-probability) evolutionary transition that might have occurred only once, in a common ancestor of all vertebrates. In contrast to the original concept, we argue that the limiting innovation was not the generation of somatic diversity, but the regulatory circuitry needed for the safe operation of amplifiable immune responses with somatically acquired targeting. Regulatory complexity increased abruptly by genomic duplications at the root of the vertebrate lineage, creating a rare opportunity to establish such circuitry. We discuss the selection forces that might have acted at the origin of the transition, and in the subsequent stepwise evolution leading to the modern immune systems of extant vertebrates.

TGF‐β Control of Adaptive Immune Tolerance: A Break From Treg Cells

“…The emergence of a higher level of selection would then suppress evolution at the lower level (e.g., depriving “domesticated” mitochondria of autonomous replication). In this context, the vertebrate adaptive immune system can be considered as a radical evolutionary innovation, as it recreates Darwinian cell‐level evolution in a multicellular organism . Such an embedded lower level selection is inherently disruptive in terms of autoimmunity unless it is tightly controlled.…”

“…To fulfill such a task, host moieties complementary to the varying PAMs need be acquired de novo, and the ensuing PAM recognition triggers a protective response that annihilates or limits the damaging effects of pathogens. As a testament of its importance, an array of adaptive immune system exists in major domains of life ranging from bacterial CRISPR/Cas (clustered regularly interspaced short palindromic repeats and CRISPR‐associated genes) to B and T lymphocytes in jawed vertebrates …”

Lineage EM Algorithm for Inferring Latent States from Cellular Lineage Trees

“…More generally, the 11 heterogeneities in the self-replication speed and the death rate as well as their inheritance from a 12 mother to daughter cells constitute the Darwinian natural selection among the cells. The natural 13 selection at the cellular level is also highly relevant for drug-resistances of pathogens and cancers, 14 the establishment of immunological memories, and cell competitions in tissues (9-13). Therefore, 15 quantification of the replicative and survival capabilities, which are often identified with the fitness, 16 from data is crucial for predicting and controlling these phenomena ruled by the micro-evolution of 17 the cells (14,15).…”

“…6 (a)), which is also reflected in the small value of the state-independent fluctuation Σ v (Eq. 259 (13)). The dissection of log τ i into each component of the latent state also indicates that x 1 and x 2 260 mainly represent the fluctuation of the division time whereas x 3 encodes its average value ( Fig.…”

Network organization of antibody interactions in sequence and structure space: the RADARS model

“…Appearance of complex multicellular life was accompanied by the evolution of a system that maintains cellular and molecular integrity in the host organism (1). The adaptive immune system is a complex system in the physical sense, being composed of a vast number of cells that engage in interactions, self-organize and -most impressively -adapt to the molecular and cellular environment.…”