Biology Reference
In-Depth Information
However, if the built-in defense mechanisms of the CNS fail, there are mecha-
nisms to permit involvement of the adaptive immune system. These changes are ini-
tiated by adhesion molecules expressed by capillary endothelial cells in conjunction
with cytokines. Both leukocytes and endothelial cells express adhesion molecules,
which slow down and stop circulating leukocytes and eventually trigger diapedesis of
the leukocytes. At sites of trauma, the BBB may be damaged, and hence blood-borne
cells will gain access to the injured tissue very quickly
[19]
.
7.2.3 Cells and Mediators of NATIM
The cells that play important roles in NATIM are: Neurons, glia cells, monocyte/
macrophages, natural killer (NK) cells, NKT cells, marginal zone (CD5) B
lymphocytes making natural antibodies, neutrophil-, eosinophil - and basophil gran-
ulocytes, platelets, mast cells, dendritic cells, Langerhans cells, Kupffer cells in the
liver, reticulo-endothelial system (RES) cells, epithelial cells. Major organs involved
are the hypothalamus, pituitary, adrenals, bone marrow, and liver; all of these organs
are activated during acute illness
[22]
.
Major cytokines are IL-1, IL-6, TNF, GM-CSF, IL-1Ra, IL-2 through -5, -IL-10,
IL-12 through -18, TGF, and interferon (IFN). Other serum components are nat-
ural antibodies, defensins, complement, acute phase proteins, fibrinogen and other
clotting factors, kallikrein, bradykinin, and the like. Injured or sick cells and tis-
sues signal the immune system and the brain by the release of cytokines (CTKs) and
chemokines (CMKs)
[23]
.
7.2.4 Other Organs/Cells That Express TLR
All leukocytes express TLRs
[26]
. TLRs are expressed in the pituitary gland
[27]
, in
the adrenal gland
[28]
, in the liver
[29]
, in mucosal epithelial cells
[30]
, in endothe-
lial cells
[31]
, in vascular smooth muscle
[32]
, and also in the cornea
[33]
. These
facts suggest that the entire body, including the CNS, endocrine organs, the liver, epi-
thelium and endothelium, and possibly even more, participate in innate immune host
defense. The CNS is capable of directly sensing infectious agents through TLRs,
and can react instantaneously by causing inflammation, the final effector response
of all immune compartments. Similarly, the pituitary produces proopiomelanocortin
(POMC) in response to LPS (TLR4 is involved), mucosal epithelial TLRs participate
in inflammation and respond to pathogens, corneal TLRs were found to fight infec-
tion, and endothelial TLRs were observed to play important roles in homeostasis of
the heart. Therefore, in addition to participating in NATIM, TLRs fulfill important
physiological functions. This is true for cytokines and also for cellular elements of
the immune system, whether natural or adaptive immune cells are considered.
7.2.5 Neuroimmune Regulation of NATIM
Both the bone marrow and the thymus are pituitary dependent. Growth and lacto-
genic hormones (GLHs) support the maturation of lymphocytes and leukocytes in
