We have studied the effects of IPR activation through analysis of mutants that have misregulated expression of IPR genes. For example, pals-22 mutants have upregulated IPR gene expression in the absence of infection (Reddy et al, 2017), and these mutants have dramatic changes in physiology, with increased resistance against microsporidia and virus infection, among other phenotypes (see below). Nearly all of the pals-22 phenotypes are reversed by mutations in the pals-25 gene, which is in an operon with pals-22. Thus wild-type pals-22 is a repressor and wild-type pals-25 is an activator of the IPR program, and we refer to them as ‘antagonistic paralogs’ (Reddy et al, 2019). We are currently investigating how pals-22 and pals-25 regulate the diverse set of phenotypes associated with the IPR, including increased pathogen resistance.