There are several approaches to studying evolutionary processes that are important to implement as we move forward to gain better insight into the role of symbiosis in shaping host immunity. First, inferences of evolutionary past often benefit from a comparative approach. In this case, comparison of immune system processes in closely related species that have evolved in the presence and absence of symbionts would be ideal. However, given the ubiquity of symbiosis in many animal groups, this approach is often challenging. Continued investigation of animal reliance on symbionts, however, may reveal ideal comparisons. The comparative approach may be easier to implement in regard to the influence of transmission mode on immune system interactions. Innate immunity is a natural, non-anticipatory, and nonspecific system that does not create a new form of memory and should be incorporated into the first evolutionary memory. This system comprises phagocyte-like cells that have broad receptors to distinguish conserved patterns of pathogens and soluble proteins and is important in all kinds of animals including vertebrates and invertebrates. The adaptive immune system collaborates with the innate immune system to shield hosts from infection.

However, the adaptive immune system generates self-reactive antibodies by targeting non-self-components, and these can give rise to autoimmune diseases when ineffectively counter selected. The immune system consists of innate and adaptive immunities that include T and B lymphocytes and the production of cytokines and antibodies in the most complex species such as mammals. The Pattern Recognition Receptors (PRRs) are of specific interest. These contain members of proteins in the nucleotide oligomerization domain that contain toll-like receptors (TLRs), leucine-rich repeats (NLRs), and gene-induced retinoic acid (RIG)-like helicases (RLHs). TLRs deserve special attention and are among the most extensive and best-studied PRRs. They are expressed on macrophages, dendritic cells, epithelial cells, and endothelial cells, where they provide quick responses including the induction of proinflammatory cytokine secretion that recruits and activates additional immune responses. Such receptors during evolution were highly conserved and first identified in Drosophila melanogaster. The TLRs are necessary for various microorganisms to defend themselves. For example, mutant Drosophila, which carries loss-of-function mutations in the Toll receptor, has been shown to be highly susceptible to infection with fungi. An anti-fungal peptide defective induction provided the first evidence that Drosophila expresses a specific receptor responsible for sensing an infection with the fungus. Based on these concepts, we suggest a way to look at autoimmune processes from an evolutionary point of view with special consideration to immune receptors that are essential for the sensing of disease-causing agents and for the fine-tuning of the resulting immune and inflammatory response. These receptors undergo constant changes in selection caused by the pressure of evolving pathogens. These pathogens stimulate the development of effective immune reactivity to maximise the pathogens' destruction while avoiding excessive immune and inflammatory responses that could lead to consequences such as autoimmunity or septic shock.

The aim of this Special Issue is to collate original research articles relating to the adaptive evolution of autoimmune genes into a coherent article collection. We aim to advance understanding in this field and highlight the significance of emerging new approaches to comprehend the importance of autoimmune diseases. Review articles discussing the current state of the art are also welcomed.

Potential topics include but are not limited to the following:

• Origin and evolution of the adaptive immune system
• Genetic events and selective pressures in adaptive immunity
• Evolutionary continuum in the host’s response to pathogens
• Bioinformatics screening of autoimmune disease genes and protein
• Epigenetic mechanisms mediate induction of innate immune memory
• Molecular evolution and phylogeny
• Evolution of animal immunity in the light of beneficial symbioses
• Potential evolutionary consequences for host immune systems
• Comparisons between animal and plant immunity
• Common molecular tools from their single-celled ancestors, both plants and animals have evolved to use some of them for immune defence
• Machine learning techniques for personalized medicine approaches in immune diseases.
• Artificial neural networks for immunological recognition.
• Autoimmune mutants and their usages in genetic dissection