Innate immunity is the first line of defense against pathogens. In animals, the Toll pathway, the Imd pathway, the complement system, and lectins are well-known mechanisms involved in innate immunity. Although these pathways and systems are well understood in vertebrates and arthropods, they are understudied in other invertebrates. In order to shed light on immunity in the nemertean Lineus ruber, we performed a transcriptomic survey and identified the main components of the Toll pathway (e.g. myD88, dorsal/dif/NFκB-p65), the Imd pathway (e.g. imd, relish/NFκB-p105/100), the complement system (e.g. C3, cfb) and some lectins (FreD-Cs and C-lectins). In situ hybridization showed that TLRβ1, TLRβ2 and imd and are expressed in the nervous system, the complement gene C3-1 is expressed in the gut and the lectins in the nervous system, the blood, and the gut. To reveal their potential role in defense mechanisms, we performed immune challenge experiments, in which Lineus ruber specimens were exposed to the gram-negative bacteria Vibrio diazotrophicus. Our results show the upregulation of specific components of the Toll pathway (TLRα3, TLRβ1, and TLRβ2), the complement system (C3-1), and lectins (c-lectin2 and fred-c5). Therefore, similarly to what occurs in other invertebrates, our study shows that components of the Toll pathway, the complement system and lectins are involved in the immune response in the nemertean Lineus ruber. The presence of these pathways and systems in Lineus ruber, but also in other spiralians, in protostomes and in deuterostomes suggest that these pathways and systems were involved in the immune response in the stem species of Bilateria.