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Biomedical subjects

B BENACERRAF

Publications and source records attributed to B BENACERRAF.

At least 55 records · Page 3Linked to original sources

Studies on hypersensitivity. IV. The relationship between contact and delayed sensitivity: a study of the specificity of cellular immune reactions.

In earlier observations with the picryl system, it was concluded that contact sensitivity was a form of delayed (cellular) hypersensitivity to conjugates of sensitizer with autologous proteins indistinguishable in its immunological mechanism from other classical forms of delayed hypersensitivity to proteins. This conclusion has been confirmed and extended with the picryl and chlorbenzoyl chloride systems. 1. It is shown that to induce a state of contact sensitivity, the minimal necessary amounts of hapten are of the same order of magnitude, whether this hapten is conjugated with protein or the free reactive chemical itself. From this, it is evident that contamination of conjugates with small amounts of unreacted sensitizer plays no part in the induction of contact reactivity by the conjugate. With the dinitrophenyl system, no contact sensitivity could be induced by the conjugates used; possible reasons for this discrepancy are discussed. 2. Animals sensitized to contact by homologous conjugate can be completely desensitized by injections of such a conjugate in large amount; a similar injection schedule has no effect on the contact sensitivity of animals sensitized with the free reactive sensitizer. 3. The capacity of heterologous (ovalbumin) conjugates to evoke anti-hapten antibodies is shown to be greater than that of homologous (guinea pig seralbumin) conjugates: the reverse is true of their capacity to induce delayed reactivity. 4. Evidence is brought forward to suggest that in animals sensitized with homologous albumin conjugates, the specificity of the delayed reaction involves more than the hapten alone, even though the carrier protein is non-antigenic on its own. The contrast with the apparent lesser specificity of the antibodies later produced is discussed.

Animals↗

In vitro studies on the interaction between mouse peritoneal macrophages and strains of Salmonella and Escherichia coli.

Virulent strains of Salmonella opsonized with normal mouse plasma are never phagocytosed as well as avirulent strains. The virulent strains of Salmonella phagocytosed after opsonization with normal mouse plasma are able to multiply within normal mouse peritoneal macrophages, whereas under similar experimental conditions the avirulent strains are killed. When virulent strains of Salmonella are opsonized with specific antiserum or plasma from BCG-infected mice, they are treated by normal mouse macrophages as if they were avirulent. Virulent bacteria opsonized with BCG plasma are phagocytosed and killed better by peritoneal macrophages from BCG-infected mice, than peritoneal macrophages from normal mice.

Animals↗

The pathologic effects of intravenously administered soluble antigen-antibody complexes. I. Passive serum sickness in mice.

The intravenous administration to mice of soluble antigen-antibody complexes in antigen excess resulted in a high incidence of glomerulonephritis and less frequently in endocarditis or arteritis. These lesions are present within 48 hours of the first of 3 injections and disappear within 2 weeks. The same pathological changes were produced with complexes prepared from either rabbit or chicken antibody. In the case of rabbit antibody, the severity of the glomerulonephritis was greater with the ovalbumin antiovalbumin system than with the BSA system. Anaphylaxis regularly occurred in mice given complexes prepared from rabbit antibody, but was not seen following administration of complexes prepared from chicken antibody. Pretreatment with cortisone diminished the severity of the glomerulo-nephritis and resulted in accumulation of amorphous, eosinophilic material within glomerular capillaries in mice injected with antigen-antibody complexes. The rabbit antibody used in these experiments failed to sensitize guinea pig skin to passive cutaneous anaphylaxis when injected in the form of soluble complexes. This indicates that these complexes do not dissociate to a detectable extent in vivo and thus favors the interpretation that complexes localize as such in the sites where tissue damage occurs. Chicken anti-mouse erythrocyte antibody produced hemolysis of mouse red cells in the presence of mouse complement. In contrast to a similar rabbit anti-serum, the hemolytic activity of the chicken antibody with mouse complement was very slight. This suggests that complement does not play an important role in the pathogenesis of these experimental lesions.

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A quantitative study of the kinetics of blood clearance of P32-labelled Escherichia coli and Staphylococci by the reticuloendothelial system.

1. The clearance of P(32)-labelled heat-killed E. coli and staphylococci from the blood follows an exponential function of the time, and the bacteria are phagocytized principally by the RES of the liver and spleen. 2. The rates of clearance of equivalent number of E. coli from the blood is rapid in rabbits and slow in mice and appears to be related to the level of antibodies in the serum of these animals. 3. Unlike E. coli, staphylococci are cleared rapidly and efficiently by the RES from the blood of mice which have a sufficient level of serum antibody against these bacteria. 4. The numbers of bacteria, phagocytized by the liver or the spleen respectively, depend upon the rate of clearance and the extent of opsonization of the bacteria. Rapidly cleared, well opsonized E. coli are removed almost exclusively by the liver, while less efficiently phagocytized bacteria are also cleared by the spleen in large numbers. 5. The rate of clearance of E. coli and the efficiency with which they are phagocyted by the RES in mice have been shown to be directly related to the level of antibody in the serum. 6. Treatment of mice with S. typhi or Serratia marcescens endotoxins increases the rate of clearance of E. coli from the blood and the level of antibody against E. coli in the serum. The enhanced clearance of E. coli can be transferred to normal mice by the serum of endotoxin-treated mice.

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The effect of high doses of x-irradiation on the phagocytic, proliferative, and metabolic properties of the reticulo-endothelial system.

The effect of moderately high doses of x-irradiation upon the reticulo-endothelial system of mice and rats was investigated. A dosage of 600 r to mice and 850 r to rats did not interfere with the ability of the RES to clear colloidal particles from the blood. However the 850 r x-ray dose to rats prevented recovery of normal phagocytic function after "blockade." In mice, 600 r interfered with the ability of the RES to respond to the usual stimulating effect of zymosan. The ability of the RES of mice which have received 600 r of x-rays to clear P(32)-labelled E. coli from the blood was not significantly altered. These mice responded poorly to immunization, as demonstrated by the slow rate of clearance of the bacteria from the blood of immunized, irradiated individuals as compared with that of immunized controls. This reflected the lowered antibody production and not deficiency of phagocytic mechanism. There was no evidence of a changed capacity of the Kupffer cells of mice which had received 600 r of x-rays to break down denatured protein enzymatically.

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