cells, organs, and at the systemic level. There is a dense sympathetic innervation
of all lymphoid organs (Dantzer 2018). The PNS regulates immunological
development (the sympathetic nervous system regulates haematopoiesis), prim-
ing (neurons influence the triggering of an immune response in lymph nodes),
and deployment (peripheral neurons associated with vessels can impact on
leukocyte recruitment into peripheral tissues) (Ordovas-Montanes et al.
2015). In response to pathogens or tissue perturbation, immune cells are
activated at the periphery and release cytokines and other inflammatory mole-
cules; these molecules have an impact on local sensory neurons and influence
signaling to the CNS (Chavan et al. 2017). Furthermore, pro-inflammatory
cytokines produced by immune cells at the periphery communicate with the
brain through afferent nerves, a process that leads to the production (by acti-
vated microglia) of other pro-inflammatory mediators in the brain itself. (Using
a perhaps slippery vocabulary, some authors say that the brain forms, via
neuromediators and immune mediators, an“image” of immune responses
occurring in peripheral tissues (Dantzer et al. 2008)).
Interactions between the nervous and the immune system can have important
functional consequences. For example, homeostatic circuits regulating tem-
perature maintenance, blood pressure, and intestinal mobility involve immune
cells. The vagus nerve is important for detecting and reporting on peripheral
immune responses and, in turn, efferent signals from the CNS are indispensable
for the regulation of inflammatory responses (Ordovas-Montanes et al. 2015).
Kevin Tracey in the 2000s proposed calling this neuroimmune network the
“inflammatory reflex”(reviewed in (Chavan et al. 2017)), a concept enriched
and discussed in subsequent research (Dantzer 2018).
Neuroimmune interactions can also involve additional actors. A major recent
example is research on the microbiome–gut–brain axis. Mouse and insect
models suggest that the microbiome influences brain development and behavior
(Sharon et al. 2016; Vuong et al. 2017; Schretter et al. 2018b), in part through
the mediation of the immune system (Fung et al. 2017). Whether this conclusion
may apply to humans remains an open question.
Crucially, neuroimmune interactions have recently been said to have an
impact on cognition. It has been proposed that cytokines play a critical role in
spatial memory (Sparkman et al. 2006) and that microglia are important for
learning and memory by promoting learning-related synapse formation through
brain-derived neurotrophic factor signaling (Parkhurst et al. 2013).
Furthermore, according to some authors, adaptive immunity influences cogni-
tion (Kipnis 2016). Mice deficient in T lymphocytes were found to exhibit
cognitive impairment in spatial learning/memory tasks and passive transfer of
mature T cells improves their cognitive function (Kipnis et al. 2004). A likely
Philosophy of Immunology 49