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Regulation of immunity and tolerance to type iii pneumococcal polysaccharide by functionally distinct immunoglobulin m anti type iii pneumococcal polysaccharide antibodies


Australian Journal of Experimental Biology & Medical Science 63(1): 19-32
Regulation of immunity and tolerance to type iii pneumococcal polysaccharide by functionally distinct immunoglobulin m anti type iii pneumococcal polysaccharide antibodies
When BALB/c mice and athymic (nude) mice are injected i.p. with pneumococcal type III polysaccharide (SIII), their antibodies as measured by passive hemagglutination (HA) are inhibited more easily by high doses of SIII than antibody measured by passive hemolysis (HL). The HA activity, due mainly to a highly avid non-complement-fixing (NCF) type of IgM, was further distinguished from the HL activity (CF-IgM, or CF-IgM plus CR hybrid IgM/A anti-SIII antibodies) by the failure of the NCF-IgM anti-SIII to bind to protein-A of Staphylococcus aureus (Sa). High-dose tolerance in the HL anti-SIII antibody response of BALB/c and athymic mice was induced only in the absence of circulating NCF-IgM anti-SIII antibodies. The presence of NCF-IgM anti-SIII antibodies formed to multiple daily increasing amounts of SIII, commencing with 0.01 .mu.g SIII, decreased the magnitude of the HL anti-SIII response to subsequent daily increments of SIII antigen injected into BALB/c and athymic (nude) mice. Thus, the effect on the HL anti-SIII response was independent of T-cells. The concomitant administration of NCF-IgM anti-SIII rendered SIII less tolerogenic in primed mice. In contrast to the HL activity, the NCF-IgM anti-SIII antibodies were induced to low doses of SIII, conferred protection against viable pneumococci, but did not precipitate the soluble antigen in agar. It is proposed that immune paralysis (as defined by the failure of SIII-injected mice to resist pneumococcal challenge) is not necessarily a condition of total unresponsiveness but is due to an absence of protective NCF-IgM anti-SIII antibodies. Thus, immune paralysis can co-exist with either the presence or absence of non-protective CF-IgM or CF-IgM/A anti-SIII antibodies.


Accession: 006288666



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