Routes of tolerance induction and persistent tolerant infections
THE CONTEXT
Tolerance depends partly on antigen administration route and can also occur naturally during persistent viral infection.
Route of administration
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The intradermal route is described as the best route for inducing tolerance, allowing antigen to equilibrate throughout the extravascular and intravascular compartments.
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The intravenous route is preferred for antigens that do not equilibrate readily or are rapidly eliminated.
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Certain haptens that are immunogenic by the intradermal route in guinea pigs are tolerogenic when given orally or intravenously.
Naturally occurring viral tolerance
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Congenital rubella and cytomegalovirus infections can show persistent viremia with decreased production of neutralising antibodies, described as persistent tolerant infection.
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In carrier mice with lymphocytic choriomeningitis infection, virus may persist in virtually all cells and tissues and pass vertically to offspring without a demonstrable immune response or pathogenic effect.
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Interrupting this tolerance by inducing antibody or injecting sensitised lymphocytes results in disease.
Overcoming tolerance and its persistence
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Tolerance can end spontaneously or be overcome by injection of cross-reacting immunogens.
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Tolerance to bovine serum albumin in rabbits can be abolished by immunisation with cross-reacting human serum albumin.
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Tolerance to living agents is generally more lasting than tolerance to non-living substances.