McDuffie, Frederic C.

Abstract Immunization of goats and mules with human thrombin resulted in an antiserum that reacted only weakly with the parent molecule, prothrombin. Some of the antibodies in this antiserum showed a greater affinity for thrombin complexed to its naturally occurring inhibitor, antithrombin-III, than for active thrombin. An antiserum against the human thrombin inhibitor, antithrombin-III, produced 2 precipitin lines against human serum but only 1 against plasma. The 2nd line in serum was shown to represent precipitation of a complex of thrombin with antithrombin-III. The neoantigens appearing in antithrombin-III after complex formation were also present in complexes prepared with purified clotting factor Xa and antithrombin-III. Since purified host (mule) thrombin was also capable of causing formation of the neoantigenic sites when complexed to human antithrombin-III, it seems likely that these determinants result from interaction in the host between the immunogens (either human thrombin or antithrombin) and the appropriate interacting host protein (mule antithrombin-III or thrombin, respectively). Studies by radioimmunoassay showed that the antibodies formed are not completely specific for the neoantigens since they also react to a lesser extent with the free proteins.

Abstract To determine the role of C5 in the spontaneous development of “autoimmune” nephritis in NZB/W mice, the F2 generation was produced and grouped according to C5 status by serum levels as determined by radial immunodiffusion—homozygous negative (cc), heterozygous (Cc) and homozygous positive (CC). In both males and females the frequency of nephritis was actually higher in mice lacking C5 (cc). When the figures for males and females were combined this difference was statistically significant (p = 0.04). Thus C5 does not contribute to the renal lesons of NZB/W mice. It may play some protective role, perhaps through some as yet unidentified anti-viral effect.

Abstract Ablation of the bursa of Fabricius in the chicken at different times and by different techniques was carried out to assess the relative effects on production of antibodies to SRBC and of IgM and IgG. In confirmation of previous work, IgG and IgG antibody production were readily inhibited by bursectomy. In contrast, IgM production was increased by the methods used unless irradiation was added. Dipping eggs in testosterone propionate at 3 days of incubation, which completely prevented development of the bursa, resulted in IgM levels at 14 wk that were 4 × those of controls but not accompanied by any increase in the level of IgM anti-SRBC. The results indicate that: 1) the bursa has a major role in the maturation from IgM to IgG synthesis, and 2) the bursa is not essential for antibody and immunoglobulin production.

Abstract Four patients with macroglobulinemia demonstrated an impaired ability to produce IgM antibody when stimulated with a relatively weak antigen, sheep cell stroma, but not with a more potent antigen, Brucellin. The explanation of this defect is unknown. It may be in part the cause of the greater-than-normal infection rate seen in patients with macroglobulinemia.

SummaryWhen 125I-labeled canine prothrombin was given to normal adult dogs intravenously, it was calculated that 240% of the plasma prothrombin crossed the capillary barrier per day, 410% of the interstitial prothrombin returned to the blood stream daily, and 79% of the plasmatic prothrombin was catabolized per day. These data are in close agreement with those observed for bovine prothrombin in calves by Takeda (1970).When derived from normal dog prothrombin, prethrombin-1 is a mixture of 2 polypeptides, one larger than the other, and both present in about equal amounts. The longer peptide, “prethrombin-1-long,” was catabolized twice as fast as prothrombin, and the shorter, “prethrombin-1-short,” 4 times faster. Prothrombin fragment-1 was catabolized by the normal dog still more rapidly.The catabolism of prothrombin was not accelerated in 3 dogs receiving continuous infusions of a thromboplastic emulsion of dog brain. Nor was the level of prothrombin in their plasma remarkably altered.