The Harry M. Zweig Memorial Fund for Equine Research

Influence of an Underlying Immune Environment on the Subsequent IgG Isotype Reponse to a Foreign Antigen

Dr. Dorothy M. Ainsworth

The primary objective of this project will be to investigate how an underlying inflammatory condition, like heaves (also known as recurrent airway obstruction (RAO) or chronic obstructive pulmonary disease, COPD), affects or biases the immune system. We will specifically examine whether a symptomatic heavey horse can develop an antibody response to a nebulized vaccine to the same degree as either a control healthy horse or an asymptomatic horse prone to heaves. Once we have quantitated the antibody response in the horses' lungs and blood, we will determine if the strength of the humoral response is correlated with the magnitude of the immune mediator (cytokine) response of the immune cells in these two compartments.

We study the immune responses in heavey horses for several reasons: This medical condition is one of the most common disorders seen in horses referred to the Cornell University Hospital for Animals. Heaves is found in middle-aged and older horses and is precipitated by exposure to hay and bedding materials. The condition, which resembles asthma in humans, is characterized by neutrophil accumulation in the small bronchioles, bronchospasm and mucus accumulation. It severely limits the athletic usefulness of these horses contributing to owner frustration and horse wastage.

Secondly, we study heaves because it is unknown if conventional vaccines, administered either intramuscularly or intranasally, might adversely affect the airway obstruction, or thirdly, whether the inflammatory condition of heaves might prevent an adequate immune response from developing.

The importance of determining whether an immunological bias is conferred from an underlying condition like heaves to subsequent antigen encounters has implications that extend beyond the study of heavey horses. For example, consider the case of a young foal infected with intestinal roundworms. As part of their life cycle, these parasites migrate through the foal's lungs, establishing a chronic inflammatory response characterized as a T helper cell 2 reaction. The ensuing T helper cell 2 environment, with production of certain immune mediators or cytokines, might deter the ability of the pulmonary and systemic immune cells to produce antibodies against either inhaled bacteria and viruses or to normally-administered vaccines. Such a phenomenon has been documented in mice, rats and guinea pigs, but not in the horse. The net result is that the Th-2 environment negatively impacts on the pulmonary and systemic health of the foal.

Understanding what conditions are optimal for the development of an immune response—what conditions enhance or diminish antibody production—is critical for improvements in equine health and in equine vaccine development.