Summary
According to fluorescent antibody observations, Fraction I injected in oil persisted in guinea pigs for 186 to 210 days. Its distribution detected with fluorescent antibody and by radioactivity differed. The latter suggested combination with antibody resulting in catabolism by the liver, elimination by the kidneys and brief storage in bone marrow not seen with fluorescent antibody. Only fixed reticular macrophages and fibroblasts were observed to ingest the antigen. It was not stored long in these cells. Many vessels, sinuses and other microscopic cavities were lined with a thick coating of the antigen. The last appearance in antibody producing centers was in the germinal centers of Flemming. Partial immunity developed 3 months after primary injection and could be restimulated at 6 months. Immunounresponsiveness of guinea pigs to Fraction I in oil was temporary; eventually a partial immunity arose.
Summary
Given a weight-adjusted dose, mice excreted an excess of Fraction I two to three times faster than guinea pigs, which explains former difficulties in detecting immunounresponsiveness in mice.
The rapidity of elimination of further Fraction I by immunounresponsive guinea pigs 90 days after a primary excess in oil may prevent further stimulation of antibody production in some animals, thus resulting in partial, rather than complete, immunity.
Hyperimmune animals were not easily made immunounresponsive. Immunity to Fraction I once established was solid and not easily overwhelmed.
Serologic response of guinea pigs to graded doses of Fraction I approaching excess 21 days after injection or over a long period after a single large excess indicates a limited plateau of antibody production to excess Fraction I.
This and previous studies indicate immunounresponsiveness of guinea pigs to excess Fraction I in oil adjuvant to be a temporary long delay in immunity resulting from a prolonged blockade of elements of the RES by finely divided state of the antigen, producing a saturation of a limited plateau of antibody production by this system. These inhibiting factors are partially overcome 3 to 6 months later by a gradually appearing antibody excess stimulated from within or by booster inoculation from without. Complete immunity was not obtained because of the rapidity of excretion of later immunizing doses, appearing slowly from the encapsulated injection site or as booster injections.
Summary
According to fluorescent antibody study of the distribution and fate of Fraction I, it may be absorbed by a variety of fixed tissues, such as endothelium of blood vessels, dead striated muscle or reticular tissue in spleen and lymph nodes. It may be absorbed by fibroblasts, fixed reticulum cells in lymph nodes and bone marrow and fat cells. It may be transported by one of two means: A large portion may flow freely in lymph or plasma, or it may be adsorbed as a thick coating on circulating erythrocytes or phagocytes. It is ingested by few mobile macrophages or microphages in quantity detectable with this method. Its presence in Bowman's capsule and convoluted tubules suggests elimination in urine. Its last site of appearance in antibody-producing organs is the germinal centers of Flemming. Its prolonged presence as a thick coating or lining in various structures suggests numerous areas of local excess that might absorb circulating antibody for a prolonged period, thus explaining the long-delayed immunity in guinea pigs given an excess of Fraction I in oil adjuvant.
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