Innate immunity

Abstract

Recent years have witnessed an explosion of interest in the innate immune system. Questions about how the innate immune system senses infection and empowers a protective immune response are being answered at the molecular level. These basic science discoveries are being translated into a more complete understanding of the central role innate immunity plays in the pathogenesis of many human infectious and inflammatory diseases. It is particularly exciting that we are already seeing a return on these scientific investments with the emergence of novel therapies to harness the power of the innate immune system. In this review we explore the defining characteristics of the innate immune system, and through more detailed examples, we highlight recent breakthroughs that have advanced our understanding of the role of innate immunity in human health and disease.

Figure 1. Integrated Human Immune System

The human microbial defense system can be simplistically viewed as consisting of three levels: (i) anatomical and physiological barriers; (ii) innate immunity; and (iii) adaptive immunity. In common with many classification systems, some elements are difficult to categorize. For example, NKT cells and DCs could be classified as being on the cusp of innate and adaptive immunity rather than being firmly in one camp.

Figure 2. Overview of TLR Signaling and the NLRP3 Inflammasome

TLR ligation initiates a signaling cascade that culminates in the translocation of the transcription factors, NF-κB and others, to the nucleus generating an acute inflammatory response. The NLRP3 (or NALP3) inflammasome is triggered by a wide variety of stimuli culminating in the activation of caspase 1 which will then cleave pro-IL1β and pro-IL18 to drive an inflammatory response. Human mutations and polymorphisms in many of the genes encoding elements of these pathways appear to alter susceptibility to infectious and inflammatory diseases.