An introduction to ecological immunology

There has been a recent call for an Extended Synthesis in evolutionary biology (Pigliucci 2007). The Modern Synthesis, which united Mendelian and Darwinian ideas about genes and natural selection, has been the cornerstone of evolutionary biology for the last 60 years (Pigliucci 2007). However, many important elements were left out of that synthesis, particularly the mechanisms whereby genetic variation is transduced into phenotypic variation. Such ‘black boxes’ still pervade biology, and for biological fields such as immunology, these black boxes are the explicit subject of interest. Many of these black boxes are so dizzyingly complex, though, that generalizations about their components, much less their architecture, are rare. This lack of generality has made it difficult to link genetic changes to immunological phenotypic variation in an eco-evolutionary context. Indeed, a few exceptions aside (Matzinger 1998), each host– parasite interaction is often considered as a case study. Enter ecological immunology or, more commonly, ecoimmunology. The focus of ecoimmunology has been to describe and explain natural variation in immune functions (Sheldon & Verhulst 1996), specifically why and how biotic and abiotic factors contribute to variation in immunity in free-living organisms. This approach is in striking contrast to most immunological research, which has typically controlled variation experimentally, sometimes at great lengths (via modifications of gene expression or the use of ultra-clean housing facilities), to ascertain the molecular and cellular details of parasite coping mechanisms. Comparative immunology has taken yet a different tack by investigating major changes in immune system organization among taxa (e.g. alternative B and T cell receptor diversity generating mechanisms) (Litman et al. 2007). These data, as well as those generated by classic immunology, have yielded great insight into how hosts control parasites (and vice versa). However, neither comparative nor mainstream immunology can explain the persistence of parasitism as the most common mode of life on Earth (Price et al. 1986) nor why some hosts remain susceptible to infection (Levin & Antia 2001). All extant and extinct organisms, no matter how elegant their immune systems, are affected by parasites (Hedrick 2004). It is in this area, understanding variation in susceptibility, that ecoimmunology has made the greatest contributions. Ecoimmunology proposes that susceptibility persists because immune defence is but one element of a context-dependent, integrated, whole-organism response to parasitism (Ardia, Parmentier & Vogel 2011; Baucom& deRoode 2011; Demas, Adamo & French 2011; Graham et al. 2011). Immune defences exist to prevent the spread of cancerous cells or impede infections, but food quantity and quality, weather, threat of predation of conflict with conspecifics, and a host of other factors can matter too (Schulenburg et al. 2009). If ecological demands are great, or if fitness can be maximized via growth or reproduction instead survival of infection, immune defences may be lowered, altered, or outright compromised. This contribution of ecology to our understanding of immunology has come in just the last 20 years (Fig. 1). Before this period, papers including the terms ecol* and immunol* together were rare in ISIWeb of Science (search 10 ⁄ 20 ⁄ 2010). Since about 1990, though, the field has grown rapidly (658 papers since 1991; Fig. 1), almost twice as fast as another ‘hot’ field, oxidative stress ecology (McGraw et al. 2010). The first paper in which the above search terms were used in a manner consistent with modern ecoimmunology concerned schistosomiasis in humans. This paper (Warren 1973), which reviewed whether age-intensity curves for schistosome infections represented evidence of memory of infections or something else, was a centrepiece of classic epidemiological theory (Anderson & May 1985; May & Anderson 1979). Not until the mid-1990s, however, did ecoimmunology mature into a recognized discipline. In 1996, one of the foundational papers for the field was published (Sheldon & Verhulst 1996), which has up until now been cited over 700 times. Sheldon & Verhulst (1996) invoked trade-offs, the allocation of limited resources among competing, costly physiological functions, as a prime cause of variation in immune defences. Trade-offs remain a prime focus in ecoimmunology, although the idea has been developed and extended quite a bit (Graham, Allen & Read 2005; Adelman & Martin 2009). Another pair of papers was also critical to the establishment of the field: one proposing a handicap hypothesis for sexually selected traits (Hamilton & Zuk 1982) and the other a physiological extension, the immunocompetence handicap hypothesis (Folstad & Karter 1992). These two papers have been cited over 1000 times each and continue to be the focus of much ecoimmunological research. Today, though, the breadth of ecoimmunological research has expanded. Trade-offs continue to take a central position, but their roles in species and individual variation (Ardia, *Correspondence author. E-mail: lmartin@cas.usf.edu