Immunobiography and the Heterogeneity of Immune Responses in the Elderly: A Focus on Inflammaging and Trained Immunity

Abstract

Owing to its memory and plasticity, the immune system (IS) is capable of recording all the immunological experiences and stimuli it was exposed to. The combination of type, dose, intensity, and temporal sequence of antigenic stimuli that each individual is exposed to has been named "immunobiography." This immunological history induces a lifelong continuous adaptation of the IS, which is responsible for the capability to mount strong, weak or no response to specific antigens, thus determining the large heterogeneity of immunological responses. In the last years, it is becoming clear that memory is not solely a feature of adaptive immunity, as it has been observed that also innate immune cells are provided with a sort of memory, dubbed "trained immunity." In this review, we discuss the main characteristics of trained immunity as a possible contributor to inflammaging within the perspective of immunobiography, with particular attention to the phenotypic changes of the cell populations known to be involved in trained immunity. In conclusion, immunobiography emerges as a pervasive and comprehensive concept that could help in understanding and interpret the individual heterogeneity of immune responses (to infections and vaccinations) that becomes particularly evident at old age and could affect immunosenescence and inflammaging.

Keywords: NK cells; human aging; immunobiography; inflammaging; macrophages; trained immunity.

Figure 1

General scheme of a bow-tie architectural module. This operational module is schematized as a bow tie due to the fact that it is composed by a conserved and relatively rigid core (“knot”) of elements and by two wings of inputs and outputs (fan in and fan out, respectively). The core can accept a wide range of inputs that are integrated according to rules and protocols specific for every bow-tie, yielding a wide variety of outputs. These features confer flexibility, robustness, and evolvability to the system. Adapted from Ref. (7).

Figure 2

The lifelong personal history of antigenic exposure (Immunobiography), represented as a Waddington Landscape, modulates the immune response to specific antigens. The response to every single antigenic molecule depends on the conditions of immune system (IS) when it meets the antigen. A variety of conditions, including socioeconomical status and antigenic ecospace, impinge upon the IS. The antigens can be met during life under different environmental conditions that can shape the immune response (i.e., what slope the ball will follow in its path). It is surmised that these environmental conditions act and are integrated as “fan in” signal by a bow tie-like module of conserved elements. These conditions include both early life and adult-late life events. As a whole, this process can lead to the creation at population level of a large heterogeneity of immune responsiveness to specific antigens.