Immunology Researchers Share Information

The Havemeyer Foundation has supported a yearly international workshop for a decade, with the goals of sharing new information and techniques of relevance to equine health, fostering research collaboration internationally, and setting directions for further collaborative study. In recent years, topics have included Rhodococcus equi pneumonia, neonatal septicemia, genetics, immunology, and equine influenza. This year's immunology workshop included a substantial number of prominent clinicians as well as researchers. The participant list read like a "Who's Who" in the world of veterinary immunology. The workshop was organized by Paul Lunn, BVSc, MS, PhD, MRCVS, Dipl. ACVIM, of the University of Wisconsin; David Horohov, MS, PhD, of Louisiana State University (LSU); Doug Antczak, VMD, PhD, of Cornell University; and Jan Wade of R&W Publications in England.

The program included three sessions--infectious diseases and immunity, inflammatory conditions, and new technology.

Immune responses are complex, and there is a fine line between induction of a beneficial response (immunity) that promotes recovery through clearance of an infectious agent, and induction of a detrimental response that results in inflammation and disease. The outcome also is influenced by the genetic makeup of the animal. Genetically controlled expression of certain receptors ("docking stations") on the surface of lymphocytes (a type of white blood cell) and specialized antigen-presenting cells is the first step in the body's ability to distinguish foreign antigens. Thereafter, genetically controlled chemical signals (cytokines) released by lymphocytes determine which direction the immune response takes, and the balance between beneficial immune and detrimental inflammatory responses.

Antczak spoke on immunogenetics, the rapidly expanding study of genes affecting and controlling the immune response. Rapid progress on the Equine Genome Project, fostered in part during previous Havemeyer workshops, is paving the way for breakthroughs in our understanding of genetic control and manipulation of immune response. In particular, equine researchers are using the human gene map to help document genes responsible for control of equine immune responses.

Travis McGuire, DVM, PhD, of Washington State University, spoke on "Immune control of equine infectious anemia virus." Horohov then emphasized the crucial role of T-lymphocytes in directing appropriate immune responses to infectious agents through cytokine signals, and the importance of these signals.

Resistance to re-infection via the inner (mucosal) lining of the respiratory tract relies heavily on local mucosal immune responses. These responses are recognized as a prerequisite to effectiveness of vaccines for respiratory pathogens such as influenza, strangles, and EHV-1. Definition of the distribution and function of the mucosal immune system of the horse and new approaches to induction of protective responses were presented as well.

To a large extent, progress in equine immunology research and vaccine development is dependent on development of reagents and techniques that permit researchers to identify and reproduce key steps in immunological pathways. Because of the small number of scientists engaged in equine immunology research worldwide and the large investment in time necessary to develop key reagents, the sharing of reagents, techniques, and information is critical.

Edward Robinson, BVetMed, PhD, MRCVS, of Michigan State University, discussed recurrent airway obstruction (heaves). Bruce McGorum, BVSc, PhD, of the Royal (Dick) School of Veterinary Studies emphasized the central role of neutrophils (white blood cells that consume foreign material) in the airways of heaves-affected horses. He described mechanisms through which neutrophil recruitment could be controlled. Laurent Couëtil, DVM, Dipl. ACVIM, of Purdue University, demonstrated that exposure to high levels of respirable dust and endotoxin for two weeks induced significant lower airway inflammation, suggesting that inhaled endotoxin might play a role in heaves in some horses.

In a computer-animated presentation, James Moore, DVM, PhD, of the University of Georgia, reviewed the complex sequence of events underlying endotoxemia in horses with colic, diarrhea, septicemia, and other septic conditions.

Rusty Moore, DVM, PhD, Dipl. ACVS, of LSU, presented evidence that an imbalance between vasodilator and vasoconstrictor substances derived from the endothelial lining of small blood vessels supplying the foot could explain the alterations in blood flow that occur in laminitis, a common sequel to endotoxin exposure and carbohydrate overload.

Benjamin Darien, DVM, MS, of the University of Wisconsin, described the role of a recently discovered molecule, P-selectin, in mediating adherence of platelets to the wall of small blood vessels during endotoxemia. He said that a P-selectin antagonist shows great promise as a therapeutic agent for modulating inflammatory reactions.

The final address featured a comprehensive review by Colorado State's Wayne McIlwraith, BVSc, PhD, Dipl. ACVS, of mechanisms underlying the common problem of non-infectious joint disease in the horse. He emphasized the damaging effects on articular cartilage and hyaluronan of inflammatory mediators, including the cytokines interleukin-1 and TNF-alpha, metalloproteinases, aggrecanase, prostaglandin E2, and free radicals.

About the Author

W. David Wilson, MRCVS

W. David Wilson, MRCVS, of the University of California, Davis, is chairman of the Biologic and Therapeutic Agents Committee of AAEP, and Edward W. Kanara, DVM, of the University of Pennsylvania, is the AAEP board liaison to that committee.

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