Neural-Immune Interactions: A Potential Area of Investigation for Marine Mammals
IAAAM 1988
Tracy Romano, BS; David Felten, MD, PhD


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.

Speaker Information
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David Felten, MD, PhD

Tracy A. Romano, BS, PhD

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