Neural-Immune Interactions: A Potential Area of Investigation for Marine Mammals
Evidence from a variety of disciplines supports the presence of a
bidirectional communication between the brain and the immune system. Stressors in experimental
animals, including psychological stressors, can alter immune function. In humans, bereavement,
depression, stress associated with care-giving to family members with Alzheimer's disease, and
the stress of examination taking in medical students, have been associated with measures of
decreased immune responsiveness. Ader and colleagues have shown that immune responses can be
conditioned classically. Direct evidence of brain influences on immune responses has been
obtained from lesion studies; discrete lesions in central autonomic sites can produce elevation
or decline in specific measures of immune response. During an immune response, specific central
autonomic nuclei demonstrate altered electrical activity and altered monoamine metabolism,
suggesting a reciprocal communication from immune system to brain.
Our laboratory has shown the presence of noradrenergic sympathetic nerve
fibers in specific compartments of both primary and secondary lymphoid organs. These nerve
fibers directly contact lymphocytes and macrophages as well as vascular and trabecular smooth
muscle. Norepinephrine in the rodent spleen fulfills the criteria for neurotransmission with
cells of the immune system as targets. Noradrenergic fibers are present in specific cellular
compartments of the splenic white pulp, including the periarteriolar lymphatic sheath (PALS),
the marginal sinus and parafollicular zones; direct synaptic-like contacts have been found
between noradrenergic nerve terminals and lymphocytes. In vivo dialysis techniques have shown
Norepinephrine concentrations of I pM in the extracellular space of the spleen. Lymphocytes
possess adrenoceptors, mainly of the 82 subclass, linked with adenylate cyclase and cAMP as a
second messenger. Noradrenergic denervation with chemical sympathectomy results in altered
measures of immunity, including decreased primary and secondary antibody responses, decreased
delayed type hypersensitivity responses, decreased cytotoxic T cell responses, increased natural
killer (NK) activity in vitro and in vivo, and increased B lymphocyte proliferation.
While most studies of neural-immune interactions have used the rat and mouse
as a model or have looked at correlative factors in humans, other studies using different animal
models are needed for comparison. The presence of unique responses or different immune
organization and neuronal patterns could reveal useful information about how these two systems
interact. Different types of stress that specific animals experience may result in specific
patterns of anatomical reorganization of the nerve fibers or altered neurotransmitter
metabolism, already demonstrated in rodents.
Me study of neural-immune interactions in marine mammals has great
applicability and relevance to those who study and work with marine mammals in captivity.
Specific forms of stress may leave these animals susceptible to a variety of immune related
disorders and infections. The psychological well-being of marine mammals may play a vital role
in their health, as it appears to do in humans. The training of marine mammals for military
purposes or for performance for research studies or aquatic theme parks needs to take behavioral
and physiological factors into account that may have an impact on the continued good health and
performance capabilities of these marine mammals.
Neural-immune interactions might shed some light on the cause for
strandings; of marine mammals that take place every year. One working hypothesis is that
specific stressors; induce a state of immunosuppression, leading to specific infections (e.g.
middle or inner ear infections) that result in a stranding. Investigating the innervation
patterns, compartmentalization, and cell composition of immune organs in stranded animals,
particularly if comparison is available with similar animals acutely drowned from misadventure
with fishing nets, might give us some direction in solving or relieving this problem.
The study of neural-immune interactions in marine mammals in captivity, or
in stranded or acutely drowned animals could shed some light on how their nervous and immune
systems interact. In the long run, we seek to determine how we can best care for the animals in
captivity, obtain optimal performance from them and find a successful approach to restoring
health and functional activity on stranded animals.