Memories of George Davis Snell (1904-1996).
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Biomedical subjects
Publications and source records attributed to G Hoecker.
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Two strains of mice, A. SW (H-2s) and A.CA (H-2f), were immunized with live trypomastigotes or epimastigotes of the Tulahuen strain of Trypanosoma cruzi or with their sonicates. By immunowestern blotting, sera from A.SW mice, but not from A.CA, recognized, in an immunodominant fashion, a 45 kDal polypeptide (Tc45) present in both epimastigotes and trypomastigotes. Since A.SW and A.CA strains are congenic for the major histocompatibility H-2 complex, recognition of Tc45 seems to be controlled by this genetic region or by gene(s) located in its immediate vicinity. Subcellular fractionation revealed that Tc45 is mainly present at the cytoplasmic compartment.
1. Resistance to acute Trypanosoma cruzi infection in mice is a polygenic character with a major factor linked to the murine major histocompatibility system (H-2). We found that F1 hybrids A.CA(H-2f)/B10.Br(H-2k) between two susceptible strains are strongly resistant. 2. Resistant B10(H-2b) and A.SW(H-2s) animals survived 60 or more days after an intraperitoneal injection of 10(4) Tulahuén strain blood trypomastigotes. The specific antibody response of these individuals increased continuously up to 100 days or more. Parasitemia reached a peak at day 8 in all strains. Thereafter, the number of blood parasites in resistant animals showed an irregular but persistent decrease. 3. Susceptible congenic B10.Br and A.CA animals showed lower levels of specific anti-T. cruzi antibodies and an increase in parasitemia until death. B10.Br mice died 14 to 20 days after infection. A.CA animals were extremely susceptible, showing a sharp and sustained increase in parasitemia starting on day 12, followed by death no later than day 15 post-inoculation. 4. We found a significant correlation between IgG levels present in serum of resistant mice from 20 days on and protection against acute death. Whole immune anti-T. cruzi serum or its purified IgG class fraction neutralized T. cruzi inocula in vitro as shown by a significantly increased survival of recipient susceptible A.CA mice. 5. This IgG protective effect is independent of the protective effect mediated by the terminal activation of the complement cascade, since the parasites were inoculated with heat-inactivated immune sera and both recipient (A.CA) and donor (A.SW) strains lack C5.
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A system of two public serum antigens, alpha and delta, whose distribution in inbred strains of mice is different from that of all serum antigens known, is described. Their distribution in the H-2 congenic and in the recombinant inbred HTG strain indicates that they are determined by a gene(s) tightly linked to H-2. Backcross tests confirmed this; only 1.1-cM recombinants were found. The gene(s) is located at the D side of H-2. The immunogenicity of the serum specificities in A/Sn animals, but not in other strains, is sex-limited. These serum antigens are also present in most tissues and, in high amounts, in red blood cells. No sex differences in the absorbing capacity of tissues or the agglutinability of red blood cells were found. All these findings indicate that alpha and delta antigens belong to a new H-2-linked system. A relationship with the recently found new class I genes is suggested.
Glutaraldehyde (GA)-treated sheep red blood cells (SRBC) or H-2-allogeneic spleen cells (SC), induced immunological memory with absent or markedly reduced primary antibody production. In contrast, a normal secondary response was obtained when GA-SRBC or GA-SC were given to mice primed with the corresponding untreated antigens. The secondary response of mice primed and boosted with GA-treated cells was relatively high with GA-SRBC, and negative or very low with GA-SC. Morphological studies of the fate of intraperitoneally injected cells showed that endocytosed GA-SRBC persisted much longer in peritoneal macrophages than untreated SRBC. Simultaneous challenge of mice with untreated and GA-treated SRBC revealed that phagocytosis and digestion of both types of cells in the same macrophage proceeded independently of each other. The primary response of mice receiving both SRBC and GA-SRBC was entirely similar to the response when SRBC alone was given.
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