Wiley-Liss Plenary Symposium Life History, Maintenance, and the Early Origins of Immune Function THOMAS W. MCDADE* Laboratory for Human Biology Research, Department of Anthropology, Northwestern University, Evanston, Illinois 60208 ABSTRACT There is compelling evidence to suggest that early environments are important determinants of immune function over the life course. While current research focuses on prox- imate mechanisms and clinical implications, an adaptationist perspective may contribute a theoretical basis for explaining, rather than merely describing, the long-term impact of early environments. Life history theory in particular, with its emphasis on the life cycle and investment in maintenance effort—of which immune function is a central component—provides a predictive framework for identifying prenatal and early postnatal factors that are likely to shape immunity. Key life history issues at these stages include avoiding death from infectious disease, investing in immune defenses that are appropriate for the local disease ecology, and optimizing competing demands for investment in immune function and growth. A series of hypotheses derived from these issues are proposed and evaluated with data from ongoing research in the Philippines and Bolivia. Ecologically-informed research on immunity is in its earliest stages, and life history theory has the potential to make important contributions to our understanding of the develop- ment and function of this critical physiological system. Am. J. Hum. Biol. 17:81–94, 2005. # 2004 Wiley-Liss, Inc. Evidence in support of the ‘‘early origins’’ hypothesis continues to mount, particularly with respect to the importance of early environments in modifying risk for cardio- vascular and metabolic disease later in life. Relatively little attention has been given to the long-term impact on immune develop- ment and function, despite the involvement of immunological processes in infectious, neoplastic, atopic, and even cardiovascular diseases (Moore [1998] Proc Nutr Soc 57:241–247; McDade and Kuzawa [2004], Langley-Evans SC, editor, Cambridge, MA: CABI Publishing). Outside the realm of bio- medicine and public health, recent work in evolutionary biology is increasingly recog- nizing the importance of ecology and life history trade-offs in shaping investment in immune defenses both within and across species (e.g., Sheldon and Verhulst [1996] TREE 11:317–321; Lochmiller and Deerenberg [2000] OIKOS 88:87–98). This article attempts to bring these perspectives together in proposing a life history frame- work for investigating the implications of early environments for the development of human immune function. At least four lines of evidence point toward the importance of prenatal and early postnatal factors in shaping human immunity. First, analysis of demographic records from the Gambia has revealed that being born in the hungry season—associated with lower birth- weights and higher postnatal disease expos- ure—increases the risk of early death by a factor of 3.7 after the age of 14.5 years, and by a factor of 10.3 after 25 years (Moore et al., 1999). The majority of these premature deaths were infectious in origin, suggesting an impair- ment of some aspect of immune function. Second, a large body of research in nutri- tional immunology has documented the immediate immunosuppressive effects of pro- tein-energy malnutrition in infancy and child- hood (Chandra, 1988; Gershwin et al., 2000; Suskind and Tontisirin, 2001). Postnatal undernutrition impairs key components of cell-mediated immunity, leads to involution ß 2004 Wiley-Liss, Inc. Contract grant sponsor: National Science Foundation Physical Anthropology Program; Contract grant number: BCS-0134225. *Correspondence to: T.W. McDade, Northwestern University, Department of Anthropology, 1810 Hinman Ave., Evanston, IL 60208. E-mail: t-mcdade@northwestern.edu Received 7 September 2004; Accepted 1 October 2004 Published online in Wiley InterScience (www.interscience. wiley.com). DOI: 10.1002/ajhb.20095 AMERICAN JOURNAL OF HUMAN BIOLOGY 17:81–94 (2005)