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How do immune systems evolve?
Immunologists have accumulated an enormous body of knowledge about the diversity of host responses to infection. NeoDarwinism successfully makes sense of a number of equally disparate facts from other branches of natural history. Yet no widely-agreed evolutionary synthesis underpins immunology.
Group members involved:
Current collaborators: Judi Allen, Andrea
Graham ,Gráinne Long
Evolutionary explanations of immunity will be of two sorts: historical description (when did adaptive immunity arise?) and analyses of how natural selection shapes patterns of immunoresponsiveness. There has been some progress on the first, but we are concentrating on the second. For instance, why does the number of worms that trigger inflammatory responses depend on worm species and differ between organs, hosts and host species? When does natural selection favour qualitatively different responses (e.g. behavioural or physiological, specific or non-specific, Th-1 or Th-2)?
Optimality modelling - in essence microeconomic cost-benefit analyses with evolutionary fitness as the currency - has had a substantial impact in some areas of biology because it can make successful qualitative and even quantitative predictions. Our long-term goal is use this approach to develop an evolutionary synthesis of the diversity of host responses. The idea that immunological phenomena can be understood in terms of the costs (immunopathology, resource use) and benefits (pathogen killing) of particular responses is implicit in some discussions of parasite-induced pathology (talk of double-edged swords and the like), but it has yet to be formalised to the point where it can be empirically tested. We are trying to do that. It is our belief that this can be best achieved with detailed analyses of particular immune trade-offs for which there are substantial background data against which to test theory, and where appropriate new experiments are possible. We are trying to resist the temptation to develop ever more elaborate mathematical models (so far successfully).
One balancing act natural selection has to optimise is the generation of T-helper cell subsets appropriate for particular infections. Mounting the wrong sort of T-helper/cytokine response to a given parasite/pathogen can exacerbate pathology. The cytokines and effector mechanisms enabled by T-helper type 1 cells work best against intracellular bacteria, for example, whereas type 2-associated cytokines and effectors work best against intestinal nematodes. Immunopathology may result if the response is not tailored to the parasite. How does natural selection minimise pathology following co-infection by two or more parasites/pathogens that require different immune responses? We believe this optimisation problem provides a tractable way develop and test our approach.
We are working on this, mostly using data on experimental coinfection with filarial worms and malaria.