Pathogen responses to host immunity: the impact of time delays and memory on the evolution of virulence

Abstract

Current analytical models of the mammalian immune system typically assume a specialist predator-prey relationship between invading pathogens and the active components of the immune response. However, in reality, the specific immune system is not immediately effective following invasion by a novel pathogen. First, there may be an explicit time delay between infection and immune initiation and, second, there may be a gradual build-up in immune efficacy (for instance, during the period of B-cell affinity maturation) during which the immune response develops, before reaching maximal specificity to the pathogen. Here, we use a novel theoretical approach to show that these processes, together with the presence of long-lived immune memory, decouple the immune response from current pathogen levels, greatly changing the dynamics of the pathogen-immune system interaction and the ability of the immune response to eliminate the pathogen. Furthermore, we use this model to show how distributed primary immune responses combine with immune memory to greatly affect the optimal virulence of the pathogen, potentially resulting in the evolution of highly virulent pathogens.

Resistance in persisting bat populations after white-nose syndrome invasion

“…This is at odds with observing lower overall fungal growth rates that could be caused either by environmental factors influencing pathogen growth, such as temperature [54], changes in intrinsic pathogen growth rate, or load-independent host resistance traits. The pattern of resistance we observed (type 2 in figure 2) could be owing to changes in bat skin microbial communities resulting in a new carrying capacity of the fungus on endemic bats [55], hostinduced reduction in resources for fungal consumption, increases in the time spent euthermic during late winter, an activation of an immune response when the pathogen reaches a fungal load threshold, or slow immune response activation by bats [56]. Regardless of which mechanism is responsible for the lower loads observed, our results suggest that resistance should increase bats' ability to survive through winter to reproduce in summer.…”

Dances with worms: the ecological and evolutionary impacts of deworming on coinfecting pathogens

“…Typically the associated theoretical work assumes that virulence is an unavoidable consequence of the pathogen's exploitation of the host, necessary for the pathogen to fuel its replication and subsequent transmission (Levin and Pimentel, 1981; Anderson and May, 1982; Bremermann and Pickering, 1983; Ewald, 1983; Frank, 1996). Although these initial models have been greatly expanded upon (Antia et al 1994; Bull, 1994; Lenski and May, 1994; Bonhoeffer et al 1996; Ganusov et al 2002; Restif and Koella, 2003; Boots et al 2004; Fenton et al 2006; Day et al 2007; Kamo et al 2007; Alizon, 2008 a , 2008 b ; Alizon and van Baalen, 2008 b ; Frank and Schmid-Hempel, 2008; Mideo et al 2008; Carval and Ferriere, 2010), they have so far ignored one ubiquitous component of virtually every pathogen's environment in natural populations: the presence of coinfecting helminths.…”

Impact of intracellular delay, immune activation delay and nonlinear incidence on viral dynamics

“…Antigentic stimulation generating CTLs may need a period of time, that is, the activation rate of CTLs response at time t may depend on the population of antigen at a previous time t − ω. Time delay describing the time needed for immune activation cannot be ignored in virus dynamics [3,8,23]. Based on such a reality, let z(t) represent the cellular immune response.…”