Perivascular Reactions in Lung and Liver Following Intravenous Injection of Streptococci Into Previously Sensitized Animals

Abstract

Intravenous inoculation of small doses of non-hemolytic streptococci into previously sensitized rabbits is usually followed by the appearance of perivascular cellular aggregates in lung and liver. The characteristic cell in these aggregates is moderately large, with vesicular nucleus, prominent nucleoli, clumped chromatin, and basophilic cytoplasm. In addition, the lesions contain small lymphocytes and granulocytes. This lesion is easily differentiated by architecture and cell content from normally occurring lymphoid aggregates, and from spontaneous rabbit hepatic cirrhosis. This mononuclear response does not occur when the intravenous dose is large enough to cause death of the animal within 24 hours. In spleen and lymph nodes the characteristic basophilic cells, which normally occur in these organs, are present in increased numbers. Following intravenous treatment alone, or sensitization without intravenous treatment, the lesions occur much less frequently, and when present are smaller and more sparsely found. Inasmuch as in the present series of experiments this lesion was not found in normal animals, and infrequently in those treated by the intravenous route alone, it is suggested that the preliminary sensitization serves to enhance the animal's reactivity to the antigen. In this way a small dose of bacteria is capable of eliciting the cellular phenomenon, which in unsensitized animals appears only when larger doses of antigen are administered over longer periods of time. Too large a dose of antigen, however, results in shock and cell death rather than proliferation.

Delayed Hypersensitivity

“…These complexes did not elicit skin reactions in normal guinea pigs. Iiitchcock et al (13) and Lawrence and Pappenheimer (14) have previously demonstrated that incubation with immune sera did not inhibit elicitation of delayed skin reactions by living streptococci in specifically sensitized rabbits and by diphtheria toxoid in the toxoid sensitive human, respectively.…”

Delayed Hypersensitivity

“…A shock-like syndrome also follows injection of large numbers of killed streptococci in rabbits previously infected with streptococci (25). Examination of the organs of such rabbits that do nol succumb within the first 24 hours following the specific challenge shows extensive perivascular infiltrations with lymphoid cells.…”

“…A similar delayed shock occurs after specific challenge of mice previously infected with Histoplasma (28). Since tuberculin and streptococcal shock occurred in sensitized animals with delayed skin reactivity to the specific antigen and were "delayed" in onset in comparison to classical anaphylactic shock, it was not surprising that these delayed shock states were considered by some to be the prototypic systemic reactions of animals with delayed hypersensitivity (25,29). There are, however, alternative interpretations possible.…”

The Clinical Uses of Human Serums Preserved by the Lyophile Process

“…These changes were found in from 75 to 95 per cent of the hearts, livers, kidneys, adrenals and spleens and to a variable degree in the other viscera of the fatal cases studied by Brody and Smith. Lesions resembling those described in scarlet fever have been produced experimentally by Hitchcock, Camero and Swift (6) by the intravenous injection of indifferent streptococci into rabbits previously sensitized to streptococci. Whether the characteristic vascular injury in scarlatina is due to circulating streptococcal toxins, as suggested by Brody and Smith, or is allergic as in the case of the experimental lesions of Hitchcock, Camero and Swift, the fact of definite visceral pathological changes in this disease is important and deserves emphasis in view of the current tendency to refer to the mildness of scarlatina and its low mortality.…”