Biology Reference
In-Depth Information
pathogen-associated molecular patterns
or PAMPs
[20,21]
), which show cross-
reactivity and may be present in microorganisms, in altered self-components, and
in pathological tissues, including cancer. On this basis, innate immune recogni-
tion should be defined as polyspecific, not nonspecific. Because the target antigen
of innate immunity is constant, it is possible to use germ-line gene-coded receptors,
which are also constant. This allows fully differentiated effector cells to react instan-
taneously to antigenic challenges, without the necessity of immunization. Homotopes
only activate the response, which is then regulated by cytokines, hormones, neu-
rotransmitters, and peptides
[22,23]
.
One may suggest that it is a perfect fit for the CNS to have its own NATIM sys-
tem. This is an ancient system, known for its capability to respond instantaneously
as soon as the target is recognized. So, when a neuron senses an infectious agent (for
instance, via its toll-like receptors), recognition is exceedingly fast and the response
follows immediately. It has been known for a long time that infection or injury will
provoke inflammation, which used to be regarded as a nonspecific defense mecha-
nism of the body. Today it is apparent that the CNS is capable of inducing inflamma-
tion by delivering to the target area pro-inflammatory neuropeptides (e.g., substance
P [SP], calcitonin gene-related peptide [CGRP], and neurokinins A and B), as well
as anti-inflammatory peptides (such as somatostatin [ST] and galanin [GAL]) that
inhibit inflammatory reactions. Inflammation attracts leukocytes and accumulates
excess nutrients, oxygen, and soluble mediators, such as hormones, neurotrans-
mitters, cytokines, and chemokines
[24]
. Because of these mechanisms, the CNS
is capable of mobilizing the immunological army locally at the site of infection
or injury, without delay. Instantaneous recognition coupled with a rapid defense
response confers a tremendous biological advantage.
We know that the CNS is sheltered from the invasion of infectious agents and
even from macromolecules by the blood-brain barrier
[17]
. Cells of the adaptive
immune system are also kept at bay and are present under physiological situations
only at very low numbers. The CNS is known to kill activated killer T cells by Fas
ligand, which triggers apoptosis
[19]
. Again, in this case the CNS relies on innate
immune defense, which is inherently there. TLRs are present on all cells of the CNS,
which for the most part are ready to act instantly and provide effective defense. In the
case of acute illness, the CNS is capable of mounting its own acute phase response,
as the choroid plexus produces acute phase proteins
[18]
.
Although our knowledge about the significance of NATIM in physiology and
pathology of the CNS is still rudimentary, it is possible to posit that the CNS is an
immunocompetent organ, as it is able to specifically recognize a target by its innate
receptors and to respond by the mobilization of immune effector mechanisms. As for
effector mechanisms, there are many to be considered. The entire immune system is
regulated by the CNS, but other mechanisms, such as the induction of apoptosis in
T cells and maintenance of a defense barrier, are also involved. The ability to pro-
duce the entire repertoire of biological mediators (autonomy) results in tremendous
regulatory potential. The nerve growth factor family, as well as members of the TNF
cytokine family, is cytotoxic mediators
[25]
. The CNS is defended by NATIM for
life. This form of immunity is never lost and provides reliable, instantaneous defense.
