Baruj Benacerraf

Immunological Specificity of the Secondary Response with Dinitrophenylated Proteins.

Summary The data presented clearly indicate that anamnestic response in both systems studied is related to the immunological backbone of the carrier protein as well as the hapten, and that the carrier protein alone injected secondarily does not cause production of antibodies directed against the hapten used for primary immunization.

Genetic Control in Guinea Pigs of Immune Response to Conjugates of Haptens and Poly-L-Lysine

Random-bred Hartley strain guinea pigs which do not respond immunologically to conjugates of hapten and poly-L-lysine mere mated with heterozygous guinea pigs which do. These responders were considered heterozygous for this trait since their mating resulted in at least one nonresponder offspring. Of 31 offspring from 10 breeding pairs (nonresponder x heterozygous responder) 14 were responders. There was no evidence that this trait is sex-linked. This finding confirms the view that, in guinea pigs, development of an immune response to the aforementioned conjugates is a genetically transmitted autosomal, unigenic Mendelian dominant trait.

Studies on the pathogenesis of experimental immune thyroiditis.

Summary 1. Among each of 2 groups of guinea pigs immunized with 50 μg and 500 μg of picrylated thyroglobulin in Freunds adjuvant respectively, 57.2% (63 of 110 animals) developed thyroiditis 17 days following the initial dose of antigen. Delayed skin reactivity to intradermal thyroglobulin was observed in 72.7% of the animals. There was no significant difference in incidence of thyroiditis and delayed skin reactivity in the 2 groups of animals. However, circulating antithyroglobulin antibody as determined by passive hemagglutination, was found in 4.6% (2 of 43 animals) in the low antigen group and 30% (18 of 60 animals) in the high antigen group.

Effect of hemorrhagic shock on the phagocytic function of Kupffer cells.

This report concerns the phagocytic behavior of the Kupffer cells in the rat during hemorrhagic studies by quantitative technics. The rate of clearance (measured by colloidal carbon) was suppressed by 50 per cent after 3 hours. Efficiency of clearance (measured by uptake of radioisotope labeled albumin and chromium phosphate) was likewise markedly below normal. This factor was not due to reduced blood flow through the liver, as evidenced by measurements made 1 hour after blood replacement. Histologic evidence suggests two possibilities: a localized impairment of Kupffer cell activity in the area about the central veins of the lobule, or an abnormal circulation through preferential pathways restricted to the periphery of the liver lobule.

The Genetic Control of the Immune Response to Hapten-Poly-L Lysine Conjugates in Guinea Pigs

That the immune response to an immunogen by an individual animal is under genetic control is evident from the results of several studies. For example, Fjord-Scheibel (1943), Carlifanti (1948), and Sang and Sobey (1954) showed a statistically significant relationship between the abilities of parents and their offspring to produce high serum titers of antibody to a given immunogen. Also, Ibsen (1959) showed that inbred strains of mice required different doses of antigen to produce a standardized immune response. Recently, Sobey et al. (1966) observed genetically transmissable differences among random bred mice to respond immunologically to bovine serum albumin. Finally, Arquilla and Finn (1965), in studies of the immune response of inbred guinea pigs to bovine insulin, found that strain 2 guinea pigs could make antibodies to an antigenic determinant of insulin to which strain 13 could not make antibodies. However, breeding studies showed complex patterns of inheritance.

Passive Acute Glomerulonephritis Induced by Antigen-Antibody Complexes Solubilized in Hapten Excess.

Summary Acute glomerulonephritis has been produced passively in normal mice by soluble antigen-antibody complexes prepared from rabbit anti-DNP Bγg which was precipitated at equivalence with DNPBSA and dissolved in excess hapten, ∊NH2DNP lysine. The fate and distribution of the injected antigen-antibody complexes and of purified rabbit antibody, which was used as a control, were studied by the fluorescent antibody technic. The complexes were rapidly and efficiently phagocytosed by the cells of the reticuloendothelial system and had largely disappeared from these cells within 24 hours. In contrast, there was only slight localization of complexes within glomeruli following a single injection, but with 3 injections in 24 hours, which resulted in production of acute glomerulonephritis, marked accumulation of complexes occurred in glomeruli; this was apparent 24 hours after the last injection. Purified rabbit antibody did not localize in glomeruli and only in trace amounts in the cells of the reticuloendothelial system.

Depression of Reticuloendothelial System Phagocytic Function by Ingested Lipids

Summary The oral administration of digestible lipids was followed by prolonged depression of reticuloendothelial system phagocytosis as measured by blood clearance of colloidal carbon. In contrast to the effects of intravenously administered lipids oral trioleate was as effective a depressant as ethyl stearate.

Studies on the Structure of Mouse Antibodies.

Summary Anti-DNP, anti-pipsyl and anti-ovalbumin antibodies have been isolated from the peritoneal fluids of individual hy-perimmunized mice. On immunoelectrophoresis, the antibody preparations appeared to contain, regardless of specificity, at least 2 families of molecules with slightly different electrophoretic mobility, possessing similar as well as distinct antigenic determinants. After reduction and alkylation in 8M urea and starch gel electrophoresis in 8M urea, the anti-hapten antibodies yielded distinct bands corresponding to L chains, in contrast normal mouse 7S γ-globulin and purified anti-oval-bumin antibodies showed smears corresponding to the zone of L chain migration.

Hexose Content of Guinea Pig γ1 and γ2 Immunoglobulins.

Summary Various preparations of normal and antibody guinea pig γ1 and γ2 globulins have been analyzed for their hexose content, using the indol method. The value obtained, when expressed in glucose equivalents, was 0.74% for both types of γ-globulin. Analysis of the different fragments obtained by enzymatic splitting of the molecule of γ2 globulin indicated that most of the hexose was contained in the fast (F) fragment obtained after digestion with papain (piece III of Porter). The fragment obtained after pepsin digestion contained very little if any hexose. The results indicate that guinea pig γ1 globulin does not correspond to the γ1A globulin of man and mouse. It is suggested that γ1 globulin represents a distinct family of im-munoglobulins, possibly also existent in other animal species, which mediates anaphylactic reactions within the species.

PROPERTIES OF GUINEA PIG 7S ANTIBODIES. VI. TRANSMISSION OF ANTIBODIES FROM MATERNAL TO FETAL CIRCULATION.

Evidence provided by several investigators (1–4) suggests that in some animal species fetal membranes select certain maternal antibodies for transmission to the fetal circulation and exclude other antibody fractions. For example, in the human, 7SΓ 2 antibodies reach the fetal circulation, but Γ 1A (β2A) and Γ 1M (β 2M) antibodies appear to be excluded (1). In the rabbit and guinea pig, fetal membranes exposed to homologous and heterologous tetanus or diphtheria antitoxin transmitted the homologous antibody more readily than the heterologous antibody(2–4). Evidence has been presented that the process of selective transmission involves a property of piece III, obtained by papain digestion of 7S Γ-globulin(5). In contrast to the significant transmission of natural diphtheria antitoxin, pepsin-digested antitoxin, lacking a major part of piece III, was transmitted to the guinea pig and rabbit fetus in only trace amounts(2, 6). Conversely, fragment III of rabbit Γ-globulin was transmitted nearly as readily as whole Γ-globulin, whereas fragments II and I were transmitted only 1/5 and 1/10 as readily as fragment III(5). Recent studies have characterized 2 types of guinea pig 7S antibody capable of reacting specifically with the same antigen but differing in electrophoretic mobility and biological properties(7,8,9). It was shown that guinea pig 7SΓ 1 antibodies sensitized guinea pigs for passive systemic and cutaneous anaphylaxis; 7SΓ 2 antibodies did not. Guinea pig 7SΓ 2, but not 7SΓ 1, antibodies fixed complement in vitro in the presence of antigen under the conditions tested and sensitized antigen-coated erythrocytes for lysis in the presence of complement. According to current concepts of the structure and function of mammalian Γ-globulins, differences between guinea pig 7SΓ 1 and 7SΓ 2 reside in the piece III (F fragment) of the antibody molecule(7). The availability of these 2 types of 7S antibodies led us to test (a) whether both antibodies were transferred through fetal membranes and (b) whether biologic properties associated with only one or the other of the antibodies would favor transmission or rejection by fetal membranes.