An
“eye” in the gut: the
appendix as a sentinel
sensory organ of the
immune intelligence
network
Kimberly A. Bazar
,
,
,
Patrick Y. Leeb
and A. Joon Yun
a Department of
Dermatology, San Mateo
Medical Center, 222 West
39th Avenue, San Mateo, CA
94403, USA
b Stanford
University, Palo Alto, CA,
USA
Abstract
Neural systems are
the traditional model of
intelligence. Their
complex interconnected
network of wired neurons
acquires, processes, and
responds to
environmental cues. We
propose that the immune
system is a parallel
system of intelligence
in which the gut,
including the appendix,
plays a prominent role
in data acquisition. The
immune system is
essentially a virtual
unwired network of
interacting cells that
acquires, processes, and
responds to
environmental data. The
data is typically
acquired by
antigen-presenting cells
(APCs) that gather
antigenic information
from the environment.
The APCs chemically
digest large antigens
and deconstruct them
into smaller data
packets for sampling by
other cells. The gut
performs the same
function on a larger
scale. Morsels of
environmental content
that enter the gut are
sequentially
deconstructed by
physical and chemical
digestion. In addition
to providing nutrients,
the componentized
contents offer
environmental data to
APCs in
mucosa-associated
lymphoid tissues (MALT)
that relay the sampled
information to the
immune intelligence
network. In this
framework, positioning
of the appendix
immediately after the
ileocecal valve is
strategic: it is ideally
positioned to sample
environmental data in
its maximally
deconstructed state
after small bowel
digestion. For
single-celled organisms,
digestion of the
environment has been the
primary way to sample
the surroundings. Prior
to the emergence of
complex sensory systems
such as the eye, even
multi-cellular organisms
may have relied heavily
on digestion to acquire
environmental
information. While the
relative value of immune
intelligence has
diminished since the
emergence of neural
intelligence, organisms
still use information
from both systems in
integrated fashion to
respond appropriately to
ecologic opportunities
and challenges.
Appendicitis may
represent a momentary
maladaptation in the
evolutionary transition
of sensory leadership
from the gut to the eye.
Relationships between
immune dysfunctions and
cognition are explored.