Human immune system variation

Abstract

The human immune system is highly variable between individuals but relatively stable over time within a given person. Recent conceptual and technological advances have enabled systems immunology analyses, which reveal the composition of immune cells and proteins in populations of healthy individuals. The range of variation and some specific influences that shape an individual's immune system is now becoming clearer. Human immune systems vary as a consequence of heritable and non-heritable influences, but symbiotic and pathogenic microbes and other non-heritable influences explain most of this variation. Understanding when and how such influences shape the human immune system is key for defining metrics of immunological health and understanding the risk of immune-mediated and infectious diseases.

Figure 1. The blood as a window for global immune system analysis in humans

Although the blood is not an immunological organ per se, it is the conduit for most immune cells circulating in the body, especially after an immunological stimulus such as vaccination, allowing even distal processes to be reflected in a blood sample that is readily accessible even in humans.

Figure 2. Variation in immune cells and proteins

a | An illustration of the observed stability of most immune cell and protein measurements over the course of weeks to months. During acute immune responses drastic changes occur, but thereafter measurements seem to return to a stable baseline. b | Distributions of six principal immune cell populations from a Stanford cohort (n = 398) of healthy adults^,. Numbers indicate minimum and maximal values observed.

Figure 3. Distribution of immune system variation in human populations

There are two possibilities for human immune system variation, either individuals are distributed continuously with respect to their immune system composition or in discrete groups, so called ‘immunotypes’.