Functional Recognition Theory and Type 2 Immunity: Insights and Uncertainties

Type 2 immunity plays an important role in host defense against helminths and toxins while driving allergic diseases. Despite progress in understanding the biology of type 2 immunity, the fundamental mechanisms regulating the type 2 immune module remain unclear. In contrast with structural recognition used by pattern recognition receptors, type 2 immunogens are sensed through their functional properties. Functional recognition theory has arisen as the paradigm for the initiation of type 2 immunity. However, the vast array of structurally unrelated type 2 immunogens makes it challenging to advance our understanding of type 2 immunity. In this article, we review functional recognition theory and organize type 2 immunogens into distinct classes based on how they fit into the concept of functional recognition. Lastly, we discuss areas of uncertainty in functional recognition theory with the goal of providing a framework to further define the logic of type 2 immunity in host protection and immunopathology.