The Evolution of the Immune System

November 30, 2020

Discussion

While there are several genetic and evolutionary factors that lead to variations in immune

response, differences within populations such as sex, age, and gut microbiome diversity can also

play a role (Barreiro and Murci 2020). Epigenetics, which involves a change in phenotype

without altering the genotype, has also become an area of interest due to its correlation with

immune response variation (Barreiro and Murci 2020). It has been proven that bacterial infection

triggers changes in DNA methylation of dendritic cells and macrophages, leading to rapid and

active demethylation at thousands of loci (Barreiro and Murci 2020).

There is still much to be discovered regarding the extent of the effects that epigenetic

changes have on the immune response. One study found that upon re-stimulation with a non-

related immune stimulus, monocytes that were stimulated with β-glucan mounted faster and had

stronger gene transcriptional responses (Barreiro and Murci 2020). Both the BCG vaccination for

tuberculosis and β-glucan can epigenetically reprogram stem cells in the bone marrow, leading to

an increased immune response with any subsequent infections (Barreiro and Murci 2020).

Genetic ancestry and lifestyle differences, such as whether populations were farmers as opposed

to hunters and gatherers, are associated with changes in DNA methylation and other epigenetic

marks (Barreiro and Murci 2020). Thus, there is reason to assume that differences in lifestyle, as

well as varying levels of exposure to pathogens, can lead to changes in epigenetics that affect

variation in immune response among populations (Barreiro and Murci 2020).

When looking at alternative selection regimes, such as polygenic adaptation and adaptive

admixture in both archaic and modern times, there have been limitations in determining the role

1
that natural selection plays on the immune system (Barreiro and Murci 2020). This is due in part

to the difficulty in identifying the specific pathogens that have appeared at certain periods in

history (Barreiro and Murci 2020). Through the analysis of ancient DNA correlating with a given

time period—such as during outbreaks of the plague—it can be possible to determine just how

much natural selection affects vulnerability to disease (Barreiro and Murci 2020).

While evident that natural selection plays a role in the immune system, more research

needs to be conducted to fully comprehend the part it plays in shaping population variation in

immune response (Barreiro and Murci 2020). Most research has focused solely on individuals of

European or African descent, which prevents a full understanding of variation in immunity

across all populations of the world, which are exposed to their own unique pathogens (Barreiro

and Murci 2020). Additionally, there lacks variety when characterizing phenotypes of immune

response, which focus primarily on gene expression. Research in the field should continue to

include variation in the epigenome as well as immune profiling of cellular populations (Barreiro

and Murci 2020).

There is growing interest in the field of innate immunological memory, which comprises

an ancestral biological process that evolved to protect organisms that lacked adaptive immune

systems (Gourbal et al. 2018). Recent discoveries have found that a tissue environment has a

greater impact on immune memory than once thought, rather than only in the bone marrow and

circulation (Gourbal et al. 2018). Many discoveries are still to be made in the area of the innate

immune system in order to understand its impact and implications for human disease (Gourbal et

al. 2018). The use of a system biology approach and the availability to conduct immunological

phenotyping on several individuals will facilitate this research, leading to a better understanding

of host defense (Gourbal et al. 2018).

2
Literature Cited

Barreiro, L.B., and L. Quintana-Murci. 2020. Evolutionary and Population (Epi)genetics of

Immunity to Infection. Human Genetics (139):723-732. https://doi.org/10.1007/s00439-

020-02167-x.

Gourbal, B., S. Pinaud, G. J. M. Beckers, J. W. M. Van Deer Meer, U. Conrath, M. G. Netea.

2018. Innate Immune Memory: An Evolutionary Perspective. Immunological Reviews

283 (1):21-40. https://doi.org/10.1111/imr.12647