Biology Reference
In-Depth Information
1.2.6 Neurogenic Inflammation: Neurokinins, Tachykinins, Mast Cells
There is much evidence for the regulation of inflammation and immunity by neuro-
peptides. Chemosensitive afferent nerves expressing the capsaicin/TRPV1 receptor
play important roles in the initiation and modulation of vascular, inflammatory, and
immune reactions. These nerves exert their efferent/local regulatory functions primar-
ily via the release of VIP, CGRP, and pain causing substance (SP) from their terminals
upon antidromic or orthodromic stimulation. The CTKs induced in the neural microen-
vironment by tissue injury or inflammation promote the release of pro-inflammatory
sensory neuropeptides and lead to augmentation of the inflammatory response. In
turn, the release of anti-inflammatory peptides from sensory nerves or from inflam-
matory cells results in inhibition of the inflammatory vascular reactions
[33]
.
Mast cells are innervated and thus serve as sensory organs for the CNS and func-
tion as effector cells in neurogenic inflammation. The complement split products C3a
and C5a (
anaphylatoxins
) cause mast cell discharge and thus signal the brain about
complement activation anywhere in the body. Similarly, the inflammatory mediator
bradykinin signals the brain by the sensory nerve pathway
[31,34]
.
1.2.7 The Brain as an Immunocompetent Member
of the INIM System
TLRs of innate immunity are expressed by neurons and also by their dendrites
[55]
.
This discovery implies that the nervous system expresses INIRs, is capable of sens-
ing directly the penetration of infectious and noxious agents into tissues, and can
respond immediately by inducing neurogenic inflammation and/or by the activation
of other immune compartments. Thus, the CNS is an immunocompetent organ, as it
is capable of recognizing an antigen directly and responding to it in a polyspecific
manner characteristic of innate immunity
[31]
.
1.3 The NISS
In addition to the CNS, all leukocytes express TLR
[55]
. TLR is expressed in the
pituitary gland
[56]
, in the adrenal gland
[57]
, in the liver
[58]
, in mucosal epithelial
cells
[59]
, in endothelial cells
[60]
, in vascular smooth muscle
[61]
, and also in the
cornea
[62]
. These observations indicate that the entire body participates in INIM
reactions. The CNS is capable of directly sensing infectious agents through TLR, and
possibly through other INIRs, and can react instantaneously by causing inflamma-
tion and mobilizing immune defense mechanisms. Similarly, the pituitary produces
propiomelanocortin (POMC) in response to LPS (TLR4 is involved), mucosal epithe-
lial TLR participates in inflammation and responds to pathogens, corneal TLR was
found to fight infection, and endothelial TLR was observed to play important roles in
homeostasis of the heart
[55-62]
. Therefore, in addition to participating in NATIM,
TLRs fulfill important physiological functions. This is true for CTKs and also for
cellular elements of the IS, whether or not natural or ADIM cells are considered
[54]
.
