Pepper & Nettle (P&N) focus on the behavioral constellation of deprivation (BCD) and provide a useful framework for understanding why certain behaviors persist under conditions of deprivation. Within this framework, they also touch briefly on physiological mechanisms related to and contributing to the BCD and its health outcomes. They note that, on average, individuals experiencing deprivation have worse health across multiple domains and suggest that this may be due to “double disinvestment” in physiological repair and behavioral investments in health. This suggestion makes sense, but it may be an oversimplification; development in a deprived environment may lead to not just disinvestment in repair and immune mechanisms but also investment into alternate kinds of immune defense and repair.

In section 4.4, P&N briefly consider how early-life stressors are associated with increased pro-inflammatory responses and mention research by Miller et al. (Reference Miller, Chen and Parker2011) suggesting that pro-inflammatory tendencies can become biologically committed through developmental processes, such as epigenetic modification. What P&N do not mention is that Miller et al. propose that this increase in inflammation might represent a predictive adaptive response that evolved in ancestral environments in which uncertainty was coupled with greater risks of injury and illness. In such circumstances, an elevation of inflammatory responses might be adaptive, despite potential costs to long-term health and survivability.

Expanding on similar ideas, it has been suggested that different types of immune response can be thought of as having different costs and benefits that vary with life history and socioecological variables (Blackwell et al. Reference Blackwell, Trumble, Maldonado Suarez, Stieglitz, Beheim, Snodgrass, Kaplan and Gurven2016; Demas & Nelson Reference Demas and Nelson2012; McDade et al. Reference McDade, Georgiev and Kuzawa2016; Sheldon & Verhulst Reference Sheldon and Verhulst1996). We can conceptualize immunity as being composed broadly of innate and adaptive components that differ in their utility and cost. Innate components are the body's first-line response to a foreign pathogen, but they are not directed toward specific strains or species of pathogens (e.g., some of the responses commonly referred to as “inflammation”). These responses require fewer start-up costs, as they are preexisting and so can respond immediately to a threat. Alternately, adaptive responses are components that are acquired during a lifetime and are directed at the particular pathogens an individual has encountered. Adaptive immunity requires time to develop; for example, after a new infection, it may take a week or two to gain full adaptive immunity. At the core, then, the costs of innate and adaptive immunity differ in their time schedules, and if time is short, a stronger innate response might be preferred (Martin et al. Reference Martin, Weil and Nelson2007). Adaptive responses also require the production and maintenance of large pools of naïve cells, randomly generated variants that may or may not match an actual antigen, and thus require continuous energetic investment. Therefore, such factors as nutritional abundance, pathogen exposure, and extrinsic mortality risk should interact to determine optimal investment in innate versus adaptive immune defenses, given the relative costs and benefits of different kinds of immunity (McDade et al. Reference McDade, Georgiev and Kuzawa2016).

Without belaboring the details, these shifts may help explain some health correlates of deprivation, in particular the incidence of chronic diseases, such as cardiovascular disease and diabetes. Inflammation contributes to these diseases by causing collateral damage in the body. However, because this damage may not have effects for many years, when extrinsic mortality is high, it may not pay to avoid it, given the short-term benefits.

The regulation of these alternate immunological strategies may also be tied to regulatory mechanisms related to stress and metabolic function. As P&N note, aspects of social deprivation and stress have consistently been linked to chronic alterations in hypothalamic–pituitary–adrenal (HPA) activity. A number of cells and signaling molecules of the immune system, particularly those implicated in inflammatory processes (e.g., IL-1β, IL-6, and TNF-α), have complementary, although inverse, diurnal rhythms to cortisol (Cermakian et al. Reference Cermakian, Lange, Golombek, Sarkar, Nakao, Shibata and Mazzoccoli2013; Chrousos Reference Chrousos2000). Under “healthy” conditions, there appears to be tight crosstalk between the circadian rhythms of these systems (Petrovsky Reference Petrovsky2001). However, chronic HPA stimulation can lead to loss of rhythmicity and diurnal blunting for cortisol and pro-inflammatory cytokines. Thus, the regulation of immunological strategies is tightly linked to broader mechanisms for regulating physiology and behavior in response to stress.

Finally, we should expect that as individuals become committed to particular immunological strategies during development, they may need to make corresponding behavioral adjustments to match their physiological conditions. Individuals monitor and make assessments based on their own physiological states; for example, self-rated life expectancy and self-rated health are reliable predictors of mortality risk, independent of objective measures (Siegel et al. Reference Siegel, Bradley and Kasl2003). It is likely that the same signaling molecules that regulate immunity, such as cytokines and cortisol, also convey information to the central nervous system. Such signals are clearly implicated in sickness behavior and depression (Shattuck & Muehlenbein Reference Shattuck and Muehlenbein2015; Stieglitz et al. Reference Stieglitz, Trumble, Thompson, Blackwell, Kaplan and Gurven2015) and might plausibly have more subtle effects on present-oriented behaviors. Thus, physiological commitment may be an important constraint, creating further feedback mechanisms that reinforce the BCD.