Variables affecting local immune response in ileal loops: role of immunization schedule, bacterial flora, and...

Several variables inherent in chronically isolated ileal (Thiry-Vella) loops in rabbits were studied for their effect on the local immune response of the intestine to live, locally invasive bacteria (Shigella X16). A much more vigorous local immunoglobulin A response to Shigella X16 was elicited when rabbits were immunized in their Thiry-Vella loops shortly after surgical creation of the loop than if a week were allowed to pass before they were immunized. Three major differences existed in Thiry-Vella loops on the day after surgery and a week later: (i) their microbial flora, (ii) nonspecific acute inflammation due to the surgery itself, and (iii) the histological appearance of the intestine. On day 1 after surgical creation of the Thiry-Vella loop, there were few bacteria in the loop, and the histology was that of normal small bowel except for mild acute inflammation due to the surgery. By day 6 after surgery, all loops contained large numbers of Pseudomonas aeruginosa and other aerobes, an atrophy of intestinal epithelium occurred, and the acute inflammation due to surgical trauma had subsided. By artificially colonizing Thiry-Vella loops with 10(8) or 10(10) live P. aeruginosa on the day of surgery, we found that the presence of these bacteria alone did not greatly diminish local immune responses to live Shigella. Furthermore, when the acute inflammation due to surgical trauma was recreated in loops 6 days old, no enhancement of the immune response was seen as compared to nontraumatized 6-day-old Thiry-Vella loops. The difference between immunization soon after surgery and a week later related to changes that occur in the loop itself with increased isolation. Finally, multiple immunizations of Thiry-Vella loops resulted in a more vigorous local immunoglobulin A response than a single immunization. These studies demonstrated that Thiry-Vella loop models can be useful in studying the kinetics of local immune responses by the intestine only if careful attention is paid to key variables inherent in the Thiry-Vella loop models themselves.