Innate immune responses are seen in a very broad range of tissues. Indeed, the Toll-like receptors (TLRs, one of the most important series of innate immune response proteins, described in detail below) are probably represented at some level in every cell in the body. Even before such systems are engaged, however, other levels of defense have important roles in mediating successful immunity.
Barrier functions served by intact epithelia are fundamental to the prevention of infection. Such barriers are augmented by secreted milieu such as airway mucus, with its ability to bind and neutralize pathogens resulting in their clearance via the mucociliary escalator.
Epithelial lining fluids often contain potent microbicidal proteins such as cathepsins, collectins, lysozyme, and defensins, with roles in pathogen neutralization, killing, and opsonization. A key part of any inflammatory response is the induction of capillary permeability, resulting in the delivery of further humoral factors such as complement to the site of tissue damage/infection. In addition to its roles in bacterial killing, complement is important in the regulation of leukocyte trafficking and inflammation.
Mice deficient in the complement protein C3 show reduced production of Th2 cytokines in asthma, though interestingly if allergen sensitization is performed epicutaneously, C3aR knockout mice show the opposite phenotype with enhanced Th2 responses perhaps mediated by alterations in antigen-presenting cell responses.
This interaction of innate and adaptive immunity is clearly complicated, and can involve multiple components of the complement system, since C5-de?cient mice also show enhanced Th2-type allergic inflammation. The role f complement fragments is thus context dependent, and recent work suggests that, for example, C5a may reduce the establishment of Th2 responses, but in models in which allergic sensitization has already occurred, inhibition of C5a might reduce disease severity. Again, these effects may involve, but are not exclusively dependent on, alteration in dendritic cell (DC) trafficking and function.
