Biology Reference
In-Depth Information
Additional communication is mediated by innervation and by recirculating leukocytes
(
Figure 1.1
). Forward and feedback (or stimulatory and inhibitory) signaling is the
rule. Under physiological conditions (homeostasis), all vital activities and values are
maintained at “normal” or physiological levels.
Pathophysiological conditions (
allostasis
) occur in response to various insults by
pathogenic microbes and agents. Pathological events may also be caused by endoge-
nous abnormalities, defects, and malfunctions. Acute febrile illness leads to the acute
phase response (APR), which is initiated by CTKs (e.g., interleukin-1 (IL-1), tumor
necrosis factor (TNF), IL-6) released from the
innate immune
(INIM)
system
.
Under these conditions, hypothalamic corticotropin-releasing hormone (CRH) and
vasopressin (VP) stimulate the HPA axis and also induce sympathetic outflow. GCs
and catecholamines (CATs) stimulate suppressor/regulatory T lymphocytes (Tsrs) and
amplify INIM. Tsrs in turn suppress
ADIM function
. The synthesis of acute phase pro-
teins is rapidly amplified in the liver, as is the synthesis of natural antibodies in special-
ized CD4 B lymphocytes. The CNS, bone marrow, liver, and leukocytes are activated,
whereas the function of other organs is reduced and catabolism prevails.
Fever
is a con-
stant symptom of APR. APR is analogous to Selye's general adaptation syndrome. It is
an emergency host defense reaction against diverse pathogenic agents, which leads to
healing in the overwhelming majority of cases
[21-28]
.
In the absence of the HPA axis, there is excessive CTK response after immune
activation/inflammation, which may have lethal consequences for the host. Even
immunization with complete Freund's adjuvant, which contains mycobacterial anti-
gens (acts on toll-like receptor-4 (TLR-4)), would kill Hypox animals (unpublished
results). Further, the sensitivity to bacterial lipopolysaccharide (LPS, also acts on
TLR-4) of adrenalectomized (ADRX) mice is elevated by 500-1,000 times when
compared to normal animals. TNF levels, induced by the same dose of LPS, were
60 times higher in ADRX mice than in intact controls. Dexamethasone restored the
resistance of ADRX mice to LPS
[29]
. These experiments indicate that stimulation
of the INIM system in the absence of the HPA axis results in excessive CTK pro-
duction, which could kill the host. Further, Korneva and Novikova showed that after
immunization, the C-fos gene is expressed in the hypothalamus. C-fos expression
indicated that the cells were activated in the hypothalamus after immunization, which
was true for several different types of antigens
[30]
. These experiments demonstrate
that there is mutual and continuous regulatory interaction between the hypothalamus
and the IS during immunization.
VP is the dominant hypothalamic regulatory hormone during chronic inflammatory
conditions. VP stimulates both PRL and the HPA axis, and thus it is capable of main-
taining both the ADIM and INIM systems in homeostasis and harmony. Indeed, our
experiments revealed that VP maintains adaptive immunocompetence. On this basis it
has been suggested that recovery from disease is regulated by VP
[28]
.
1.2.2 INIM-ADIM Interactions
It is very well established that monocytes and macrophages, which are related cells,
play a fundamental regulatory role in the INIM system and also present antigen to
