debris, many immune-mediated repair mechanisms, and the downregulating
action of regulatory T cells, among many other phenomena. In other words, the
claim that the immune system does not respond to self components is not true.
There exists in fact a continuum from autoreactivity (interactions between
immune receptors and endogenous motifs) to autoimmunity (the triggering of
an effector response targeting endogenous motifs) and to autoimmune diseases
(only the latter situation is pathological; it consists in the destruction of endo-
genous components, in a sustained manner and on a large scale–a given organ
or even the whole organism in the case of systemic autoimmune diseases such as
lupus) (Pradeu 2012).
Second, many genetically foreign entities are not eliminated by the immune
system and are instead actively tolerated via regulatory immune responses. This
includes examples such as foeto-maternal tolerance and various forms of
chimerism, but also, and most crucially, immunological tolerance to a large
number of bacteria, archaea, viruses, and fungi at all of the body’s interfaces,
including the gut, skin, lungs, sexual organs, and so on (Hooper and Gordon
2001; Chu and Mazmanian 2013; Virgin 2014; Chen et al. 2018). These resident
entities, which are found in almost all living things in nature, are often referred
to as the“microbiota.”Contrary to what was thought for many years, these
microbes are not“invisible”to the host immune system. The immune system
interacts and develops an active dialogue with them, which leads to the trigger-
ing of a complex balance of effector and immunoregulatory mechanisms. In
many cases, the host immune system facilitates the establishment and stability
of certain components of the microbiota (Round and Mazmanian 2009;
Donaldson et al. 2018). Importantly, microbial molecular patterns that were
conceived for a long time as pathogenic signatures can also mediate tolerogenic
immune responses (Sansonetti and Medzhitov 2009). All this confirms the
centrality of the phenomenon of immunological tolerance, especially to the
microbiota, in today’s immunology (Pradeu and Carosella 2006a; Pradeu 2012).
Immunological interactions between host and microbes enable, in general,
a peaceful coexistence between these two partners. It is estimated that a human
host, for example, is made up of as many bacterial cells as its genetically self cells
(Sender et al. 2016). Yet the most central point is not so much the number of these
resident microbes as what they do in the organism. The involvement of bacteria in
digestion has been known for decades, but recent research has shown that resident
microbes play a major and sometimes even indispensable role in host activities as
diverse as development, metabolism, defense, tissue repair (McFall-Ngai 2002;
Xu and Gordon 2003;McFall-Ngai et al. 2013), as well as many other processes,
including behavior (Sharon et al. 2016; Vuong et al. 2017; Schretter et al. 2018a).
Thefitness benefit for microbes consists generally in particularly favorable niches,
18 Elements in the Philosophy of Biology