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  • Title: Mechanism of induction of immunological tolerance. V. Priming and tolerance with small doses of polymerized flagellin.
    Author: Shellam GR.
    Journal: Immunology; 1969 Jan; 16(1):45-56. PubMed ID: 5770810.
    Abstract:
    The particulate antigen, polymerized flagellin, was shown to be effective both in immunological priming and in inducing tolerance in newborn Wistar rats. The following results were obtained: (1) A single injection of 100 ng or more at birth caused priming without a primary response. A secondary response could be elicited 7 or more days after birth with a dose of 10–100 μg. (2) Daily injections of 100 ng to 1 μg/g body weight of polymerized flagellin during the first 2 weeks of life abrogated the priming effect and in fact gave rise to a state of high dosage-zone immunological tolerance. (3) The injection of 1 μg to 10-5 pg/g body weight/day into newborn rats for 2 weeks gave rise to two zones of tolerance separated by a slight `immunity hump', which suggested the presence of some primed cells but fewer virgin cells following these intermediate doses. (4) The low zone of tolerance was induced by a dose of 10-4 pg/g body weight/day, which was equivalent to an initial antigen concentration in the animal of about 10-20 M, if one adopts the simplified assumption that polymerized flagellin has a molecular weight of 10 × 106. High zone tolerance was induced by doses of 100 ng/g body weight/day or more and the immunity region by 1 ng/body weight/day. (5) In the low zone, polymerized flagellin appears to induce tolerance even better in newborn rats than the lower molecular-weight monomeric flagellin. The extremely small amounts which are effective are difficult to explain, but raise the possibility of some antigen concentrating mechanism.
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