Biology Reference
In-Depth Information
In 1975, using a classical conditioning paradigm, Ader and Cohen
[7]
showed for
the first time that behavior could influence an immune response. This finding also
suggested that such an association might have biological relevance for the cause and
treatment of disease, such as was reported for lupus
[8]
. Besedovsky and DelRey
[9,10]
later showed that the sympathetic nervous system (SNS) played a role in
modulating the magnitude of a primary antibody response, suggesting one possible
mechanism by which behavior might influence the level of immunity. Besedovsky
and DelRey
[11,12]
also showed that antigen exposure caused a change in the firing
rate of neurons within the hypothalamus, which allowed activation of the SNS. We
now know that the brain communicates with cells in the periphery through two well-
characterized mechanisms: namely, the SNS and the neuroendocrine system. Felten
and his colleagues
[13,14]
provided an anatomical basis for the association between
immunity and SNS activity by showing that every lymphoid organ is innervated with
sympathetic nerve fibers and that nerve terminals are located within the area where
immune cells reside. Radioligand binding analysis and pharmacological approaches
confirmed that adrenergic receptors that bind norepinephrine (NE) are expressed on
immune cells
[15]
. These findings and many others set the stage for the establish-
ment of an entirely new field of study focused on the role played by the SNS in mod-
ulating the immune response (
Figure 5.1
). It has been proposed that a dysfunction
in any part of the communication between the nervous and immune systems might
eventually mediate the development and/or progression of a disease state, but such an
association remains inconclusive
[16,17]
. The latter limitation is further complicated
by the fact that the nervous and immune systems are often studied as separate disci-
plines, which contributes much to an understanding of how each system functions
autonomously, but not to an understanding of how a communication between the two
systems might be clinically relevant.
This chapter specifically focuses on the association that exists between the SNS
and the immune system. Documentation for such an association includes data to
show that lymphoid tissue is innervated with sympathetic nerve fibers containing NE
that is released when antigen enters the immune system, that immune cells express
receptors for NE, that engagement of these receptors on immune cells activates a cas-
cade of signaling intermediates to affect gene expression, and that changes in gene
expression are associated with changes in immune-cell activity and function.
5.2 Innervation of Lymphoid Tissue
The SNS is typically associated with the physiological “fight or flight” response,
because it is involved in the regulation of cellular activity in all major organ sys-
tems, especially during times of critical need. Neuroanatomical and neurochemi-
cal data confirmed a structural basis for sympathetic neural input into the immune
system (reviewed in Ref.
[18]
). Using a retrograde transport technique, it was
found that sympathetic innervation of lymphoid tissue stemmed from sympathetic
