Immunity: defense against infections essential for all living organisms

All organisms need protection against infection. Bacteria are often primarily seen as infectious agents, but they also need protection against bacterial viruses, so-called bacteriophages. To this end, bacteria have developed very complex defense systems, including apoptosis-like mechanisms, restriction enzymes, and even adaptive-type mechanisms involving immunological memory of immune responses through a system called CRISPR–Cas. An earlier dominating view was that adaptive immunity in eukaryotes only exists in jawed vertebrates, as their immune system includes the classical and highly variable immunoglobulins (Igs) and T-cell receptors (TCR). However, other types of variable molecules, which may be involved in immunity, have also been identified in insects, snails, lancelets, plants, sea urchins, and jawless fishes. Interestingly, fishes without jaws, such as the hagfish and lamprey, have a very complex adaptive immunity built on lymphocyte-like cells and variable lymphocyte receptors (VLRs). Notably, the variability of these VLRs has been estimated to be in the same range as Igs and T-cell receptors. This illustrates that very diverse strategies have been used to create an adaptive immune system in different organisms, indicating potent convergent evolution. Vertebrate immunity includes both adaptive and non-adaptive components, which work closely together to form a very powerful immune system for defense against infections. In contrast to adaptive immunity, the majority of the non-adaptive innate defense mechanisms, such as pattern recognition receptors, antimicrobial peptides (AMPs), iron-binding proteins, the complement system, and lysozymes, can be traced back to early eukaryotes. Immunity of invertebrates seems to rely almost entirely on innate defense mechanisms, while the presence of complex adaptive mechanisms in invertebrates, such as the VLRs of jawless fishes and Igs and TCR of jawed vertebrates, is questionable. This review summarizes old and recent findings of importance for our understanding of how immunity became an integrated part of all living organisms, from bacteria to humans, and the very different strategies that different organisms use in the protection against infection.