A multi-scale approach toward understanding immunity and survival
Friday seminar by Simon MacKenzie from University of Stirling, UK
Individuals within a population suffer from different degrees of infection both in severity and occurrence. This is understood as an individual’s capacity to mount a coherent immune response to the causative agent. Understanding individual susceptibility to disease is a major challenge in biological research with significant implications for animal and human health. To understand the complex interactions between healthy and disease states it is of utmost importance to address variation within the population at different biological scales under relevant environmental conditions. Understanding the variation within a population in response to external perturbation, such as pathogen invasion, is therefore central to understanding adaptation and survival.
Firstly, at a cellular level, the current paradigm for organisation of the immune response suggests that the cells, leukocytes, of the immune system are organised into PRR-driven networks and multi-cellular effector modules that act in a coordinated fashion to eliminate invading pathogens from the organism. From our studies describing transcript diversity uncovered by RNA-Seq, one is tempted to speculate that circulating erythrocytes may constitute a regulatory tissue interface between physiological compartments in the organism with largely unknown properties. Data shows that nucleated erythrocytes from two vertebrate groups spanning significant evolutionary time possess the cellular and molecular machinery to specifically respond to pathogens and likely contribute to the regulation of an immune response. Therefore, this ability may well extend to all non-mammalian vertebrates.
Secondly, gene-environment interaction studies using the experimental model fish, the zebrafish (Danio rerio), have shed light upon the underlying dynamics of molecular mechanisms involved in the immune response. Fish are ectothermic, as are the vast majority of animal species, and can only manipulate their body temperature by choice of an appropriate environmental temperature. Under infectious conditions, fish express behavioural fever where thermo-coupling of the immune response, at a gene-environment level, acts to increase the efficiency of the response to infection. This leads to increased survival.
Thirdly, consistent individual variability in behaviour and physiological response to challenge over time and context referred to as animal personality has been reported within animals of the same species, sex and population including fish. Two distinct animal personalities, proactive and reactive, have been described and individuals display significant differences in stress reactivity including neural and hormonal regulation. Differences in disease susceptibility have been recorded in these phenotypes. Current approaches that do not account for phenotypic variation in a defined and coherent environmental context will not provide an understanding of the underlying mechanistic link between individual variation, the environment, the immune response and disease resistance. Our aim is to explore the interface between environmental complexity and the individual’s capacity to adapt and meet these demands in the context of the immune response and survival. Thus our approach uses a multi-layered approach to develop, validate and parameterize an integrative model linking animal personality and gene-environment interaction to disease resistance/susceptibility within a population. We aim to further understanding of the role of the immune system, its functional organisation and response leading to a more informed hypothesis toward the evolution of the protectome in vertebrates.
Institute of Aquaculture, University of Stirling, UK