The Role of Immunity in the Pathogenesis of Experimental Hematogenous Pyelonephritis

Abstract

Hematogenous pyelonephritis was produced in rats utilizing multiple strains of Escherichia coli, a strain of Klebsiella pneumoniae, and a strain of Proteus mirabilis. Three patterns of hematogenous pyelonephritis occurred which represent an interrelationship between an immune response to the infecting bacteria and the development of obstructive uropathy as a consequence of infection. First, the course of pyelonephritis due to strains of Escherichia coli was acute, self-limited, and associated with the development of circulating agglutinins. Following healing, this pattern of infection was associated with acquired resistance to reinfection with the same bacterial strain. Second, the course of pyelonephritis due to a strain of Klebsiella pneumoniae type C was chronic. This infection was not associated with the production of circulating agglutinins against encapsulated strains. Acquired resistance to reinfection by the homotypic strain could not be demonstrated following eradication of infection but was produced by the passive transfer of concentrated antiserum. Third, pyelonephritis due to Proteus mirabilis was associated with circulating agglutinins and resistance to reinfection with the same organism following eradication of infection, yet the course was chronic. The chronicity appeared to be the consequence of obstructive uropathy resulting from calculi which developed during the course of the infection. Resistance to reinfection was demonstrated in infections with strains of E. coli and P. mirabilis. The resistance is associated with specific immunity as demonstrated by the observation that: (a) it is type-specific, (b) it is of at least 3 months' duration, and (c) it can be passively transferred by means of rabbit antiserum. Since K. pneumoniae failed to evoke capsular antibodies in the rat, resistance to infection with K. pneumoniae was produced only by means of passively transferred concentrated rabbit antiserum and not by prior infection. Immunity can be demonstrated to have a significant role in the pathogenesis of experimental hematogenous pyelonephritis only in the absence of obstructive uropathy.

Local immune response in experimental pyelonephritis

“…Studies in experimental animals have demonstrated that immunity may play a significant role in the pathogenesis of pyelonephritis (41)(42)(43)(44)(45). Pyelonephritis produced with Escherichia coli or Proteus mirabilis was associated with the development of circulating agglutinins and resistance to both hematogenous and retrograde reinfection with the same organism (43,44).…”

“…Pyelonephritis produced with Escherichia coli or Proteus mirabilis was associated with the development of circulating agglutinins and resistance to both hematogenous and retrograde reinfection with the same organism (43,44). The studies of Arana, Kozij, and Jackson suggested that while resistance to reinfection could be demonstrated in experimental retrograde pyelonephritis, the protection achieved after immunization or previous infection appeared to be independent of the level of serum antibody (45).…”

“…Unpublished observations. Persistent bacteriuria may be the result of infection with microorganisms which do not elicit a significant immune response such as Klebsiella pneumoniae, or the protective effect of locally synthesized antibody may be -nullified in the presence of obstruction (9,43,46). Thus, these experiments clearly demonstrate that with the development of a chronic inflammatory response, a nonlymphoid organ such as the kidney is capable of immunoglobulin synthesis.…”

Endotoxin Tolerance. Ii. Its Occurrence in Patients With Pyelonephritis*

“…The present data suggest that this relatively benign clinical course may partially result from tolerance to the effects of endotoxin in addition to the development of specific antibodies to the infecting organism (22,23). The time of the onset of tolerance in pyelonephritis is uncertain, but it seems likely that the continued renal infection serves to maintain the tolerant state.…”

Studies on the Epidemiology of Escherichia coli Infections. V. Factors Influencing Acquisition of Specific Serologic Groups*

“…However, whether 0 antibody exerts protective action in E. coli infections has been controversial. Although Sanford, Hunter, and Souda (25) have been able to induce immunity to experimental E. coli pyelonephritis by means of both active and passive immunization, others have cast doubt on the significance of these antibodies because of the persistence or recurrence of urinary tract infections with the same serologic strains in patients with high homologous antibody titers (26)(27)(28). In the present study, antibody titers obtained on admission from the 33 patients who converted to intestinal carriage of E. coli 04, 06, or 075 were approximately equal to those found in hospitalized patients not acquiring these strains.…”