Background

Background

Homeostasis is threatened by infection with agents such as viruses and bacteria. Homeostasis is also threatened by physiological threats and/or psychological insults, such as a car crash and/or depression. The terrorist attacks on the United States, occurring on September 11, 2001, and the subsequent anthrax deaths, represent physiological, psychological, as well as infection-induced threats to homeostasis. In response to such threats, immune cells are enlisted to clear infectious agents and other antigens, while cells of the nervous and endocrine systems are enlisted to preserve vital non-immune organ function. Antigen is cleared after a series of immune cell activation events, including the release of cytokines. Vital non-immune organ function is preserved through the release of neurotransmitters and hormones that regulate the tempo of organ cellular activity, such as heart rate, blood pressure, and our sense of well-being. It is well accepted that neurotransmitters and hormones synergize with each other to maintain homeostasis, while biologic mediators from the immune system are often thought to operate autonomously to sustain immune homeostasis. However, the latter belief has been increasingly challenged.

Data collected over the past 30 years show convincingly that a functional communication exists between the immune, nervous, and endocrine systems. For example, each organ system contains nerve fibers that release neurotransmitters and cells that express hormones, cytokines, and receptors for biological mediators that, when stimulated, affect the level of cellular activity (reviewed by Ader, Felten, and Cohen, 1990, Annual Review Pharmacology Toxicology, 30:561-602; Kohm and Sanders, 2001, Pharmacological Reviews, 53:487-525, Kiecolt-Glaser et al., 2002, Annual Review Psychology, 53:83-107 and Webster, Tonelli, and Sternberg, 2002, Annual Review Immunology, 2002, 20:125-63). However, data supporting a role for a neuro-endocrine-immune interrelationship in the etiology or progression of a clinical condition are circumstantial. An age-related decline in lymphoid  tissue innervation may be partially responsible for the increased incidence of autoimmunity or the increased susceptibility to infection associated with aging. On the other hand, an age-related decline in immune function may partially explain the behavioral and cognitive dysfunction associated with aging. It is also possible that the release of neurotransmitters and hormones in the lung during an allergic response is partially responsible for the worsening of allergic symptoms in some individuals. Although these possibilities are suggested by experimental findings, they emphasize the need for a better understanding of the mechanisms by which one organ system impacts the functioning of another to either maintain homeostasis or provoke the development and/or progression of immune-, neural-, and endocrine-associated clinical conditions. However, progress in the study of these mechanisms has been slow because the immune system is often studied outside the context of the body as a whole, i.e., the body working as a unit to protect itself from danger.

To address this limitation, the areas of neuroimmunology, neuroendocrinimmunology, neuroimmunomodulation, and psychoneuroimmunology were pioneered so that disciplines outside of classical immunology could design novel approaches to address specific hypotheses related to the neuro-endocrine-immune interrelationship. Thirteen scientists at The Ohio State University, trained in the classical disciplines of immunology, virology, endocrinology, psychology, neuroscience, and pharmacology, work together to conduct research in all four of these subdisciplines of immunology in an integrative manner. The overall goal of our training program is to encourage and support broad-based, early-stage training in integrative immunobiology using an institutional training grant mechanism. It is expected that our training program will enhance the knowledge base in basic and disease-related research. We propose to provide an opportunity for both predoctoral and postdoctoral trainees to obtain comprehensive research training in this interdisciplinary field. An environment is in-place at The Ohio State University in which trainees learn the various experimental techniques, research design, and conceptual approaches necessary to investigate and answer important research questions in this field of study.

Trainees will learn basic immunology, with an emphasis on the euro/endocrine/behavioral relationship, using human subjects, animals, and tissue culture model systems. Our multidisciplinary program is designed to contribute to the development of research expertise in health-related problems, as well as in basic cell and molecular biology, with an emphasis on the relationship between the three organ systems. The research expertise that is necessary to perform such studies is provided by the participation of researchers in various discipline specialties. Training the next generation of scientists/clinicians to understand the mechanisms by which these three systems relate to each other in order to maintain immune homeostasis is what our program is all about.