Oscillations in the immune system

Oscillations are surprisingly common in the immune system, both in its healthy state and in disease. The most famous example is that of periodic fevers caused by the malaria parasite. A number of hereditary disorders, which also cause periodic fevers, have also been known for a long time. Various reports of oscillations in cytokine concentrations following antigen challenge have been published over at least the past three decades. Oscillations can also occur at the intracellular level. Calcium oscillations following T-cell activation are familiar to all immunologists, and metabolic and reactive oxygen species oscillations in neutrophils have been well documented. More recently, oscillations in nuclear factor kappaB activity following stimulation by tumor necrosis factor alpha have received considerable publicity. However, despite all of these examples, oscillations in the immune system still tend to be considered mainly as pathological aberrations, and their causes and significance remained largely unknown. This is partly because of a lack of awareness within the immunological community of the appropriate theoretical frameworks for describing and analyzing such behavior. We provide an introduction to these frameworks and give a survey of the currently known oscillations that occur within the immune system.