Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
The self-nonself discrimination is germline encoded for defense mechanisms, but it is somatically learned for the immune system and this is the fundamental difference between the two. When referring to the defense mechanisms of vertebrates, immunologists like to use the term "innate immune systems" to describe the germline encoded class of defense mechanism. It was the acquisition of a somatically learned S-NS discrimination during vertebrate evolution that permitted the immune system to develop large recognitive repertoires compared to those of defense mechanisms. This seemingly boundless immune repertoire has fascinated immunologists for almost a century. Today we have a better understanding of the size and function of the antibody repertoire. Humoral antibody effector functions depend upon secreted immunoglobulin and the concentration of antibody must reach a minimum effective threshold in a short enough time to stop a growing pathogen before it becomes lethal. This requires that initially an equivalent number of B-cells per ml respond to the pathogen. This number of B-cells must respond for each and every milliliter of animal. Consequently, the humoral immune system must be iterated. This straightforward conclusion has far reaching implications, some of which are explored in this review.