The role of constraints and limitation in driving individual variation in immune response

D.R. Ardia, H.K. Parmentier, L.A. Vogel

Research output: Contribution to journalArticleAcademicpeer-review

70 Citations (Scopus)


1. Life history theory predicts that immunity should be plastic and reflect environmental contexts. However, individual variation in immune investment may arise not just because of individual adjustment, but because of developmental, physiological, genetic or immunological constraints which lead to non-adaptive responses by limiting or eliminating flexibility in immune investment. Constraints can arise because organisms are single integrated units with interconnected and interacting components, in which physiological and genetic control mechanisms may limit or constrain immunity. We review some of the key underlying genetic and physiological factors that may constrain the occurrence and intensity of immune responses. 2. A major part of individual variability may rest on variation in genetic background. Genetic-based constraints can limit or influence immune responses, particularly through pleiotropy and epistatic interactions. In addition, genetic variation, an important driver of variation in antigen recognition and immune system polarization, can be constrained through linkage disequilibrium and genetic drift. Epigenetic changes can also constrain or limit immune responses in future generations based on individual experience. 3. The immune system itself can influence individual flexibility in immune investment. Throughout development individuals face tradeoffs within the immune system that favour the expression of one trait at the expense of another. Ontogenetic differences can cause juveniles and adults to produce entirely different immune responses to the same pathogen. T-helper 1 (Th1)/T-helper 1 (Th2) polarization during infection also imposes constraints upon an individual’s immune responsiveness, with the consequence that hosts cannot simultaneously mount strong responses using both Th1 and Th2 cells. In addition, evidence suggests that flexibility in immune responses becomes constrained with age through accumulation of memory cells at the expense of naïve cells, decreased function of cells involved in adaptive and innate immunity, and programming of HPA-immune interactions. 4. In summary, selection on a particular immune trait can have effects on other immune components or phenotypic characters, as revealed by artificial selection studies. In particular selection for increased investment in compartments of the immune system leads to decreased investment in other competing life history functions and/or marked changes in other immune components. The role of past experience, even the past experience of parents, may limit and constrain immune responses through influencing the ontogeny of immunity, as well as through epigenetic influences.
Original languageEnglish
Pages (from-to)61-73
JournalFunctional Ecology
Issue number1
Publication statusPublished - 2011


  • red-blood-cells
  • major histocompatibility complex
  • primary antibody-response
  • quantitative trait loci
  • regulatory t-cells
  • sheep erythrocytes
  • natural-selection
  • drosophila-melanogaster
  • evolutionary ecology
  • divergent selection

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