What do primary immunodeficiencies tell us about the essentiality/redundancy of immune responses?

Advances in genomics and medicine have enabled the identification of (currently) 346 primary immunodeficiencies (PIDs) caused by mutations in 336 different genes. Most of these PIDs are monogenic conditions with Mendelian inheritance. Given this large number, it is possible to analyze the distribution of PIDs associated with infections and/or immunopathology according to the nature of the defect - even though this exercise can be challenging and arguable because of the pleiotropic nature of some gene products. The results of this analysis nevertheless strongly suggests that innate immune responses (mediated by pattern recognition receptor (PRR) engagement) are largely redundant, whereas adaptive immune responses are essential. Conversely, gain of function is more frequent in PRR-mediated immune responses than in adaptive immune responses - suggesting that robust innate immune pathways are less stringently regulated than energetically costly and potentially harmful adaptive immune responses.