Parasites and immune responses: Memory illusion?

Immunological memory responses to intracellular protozoa and extracellular helminths govern host resistance and susceptibility to reinfection. Humans and livestock living in parasitic disease endemic regions face continuous exposure from a very early age that often leads to asymptomatic chronic infection over their entire lifespan. Fundamental immunological studies suggest that the generation of T-cell memory is driven by tightly coordinated innate and adaptive cellular immune responses rapidly triggered following initial host infection. A key distinguishing feature of immune memory maintenance between the majority of parasitic diseases and most bacterial or viral diseases is long-term antigen persistence. Consequently, functional parasite immune memory is in a continuous, dynamic flux between activation and deactivation producing functional parasite killing or functional memory cell death. In this sense, T-cell immune memory can be regarded as "memory illusion." Furthermore, due to the finite capacity of memory lymphocytes to proliferate, continuous parasite antigen stimulation may exceed a threshold level at some point in the chronically infected host. This may result in suboptimal effector immune memory leading to host susceptibility to reinfection, or immune dysregulation yielding disease reactivation or immune pathology. The goal of this review is to highlight, through numerous examples, what is currently known about T-cell immune memory to parasites and to provide compelling hypotheses on the survival and maintenance of parasite "memory illusion." These novel concepts are discussed in the context of rationale parasite vaccine design strategies.