A. E. Axelrod

RELATIONSHIP OF PYRIDOXINE TO IMMUNOLOGICAL PHENOMENA.

Publisher Summary This chapter reviews the present status of the role of pyridoxine in various immunological phenomena and discusses recent experiments conducted in the laboratory dealing with the mode of action of this vitamin. Production of circulating antibodies as well as the state of delayed hypersensitivity is impaired in pyridoxine deficiency. The effect of this deficiency upon a delayed hypersensitivity reaction is illustrated by the prolongation of skin homografts in pyridoxine-deficient rats. The application of this deficiency state in the production of immune tolerance with splenic cells has been demonstrated and its possible clinical value indicated. The chapter describes experiments in which tolerance was achieved by administering ribosomes or RNA to newborn mice and microsomal RNA to adult, pyridoxine-deficient rats. It is hypothesized that specific messenger RNA associated with ribosomes initiates synthesis of donor transplantation antigens within the host. Pyridoxine deficiency again functions to provide in the adult the necessary state of immunological inertness that is already present in the newborn. Clinical application of such cellular components involved in synthesis of specific proteins, as well as utilization of the transplantation antigens themselves, has been projected.

Antibody production to diphtheria toxoid in vitamin deficiency states.

Summary Antibody response to purified diphtheria toxoid in vitamin deficient rats and their respective controls has been determined. Impairment of antibody response was noted in pantothenic acid, pyridoxine, pteroylglutamic acid, biotin, riboflavin and vit. D deficiencies. Vit. A deficiency had only a moderate effect and thiamine-deficient rats showed normal antibody titers.

Cellular antibody synthesis in thiamin, riboflavin, biotin and folic acid-deficient rats.

Summary The formation of splenic antibody-forming cells was determined by the Jerne agar-plaque technique in normal rats and in rats deficient in thiamin, riboflavin, biotin or folic acid immunized with sheep erythrocytes. The number of antibody-forming cells was reduced in all deficiency states with thiamin deficiency having the least effect. This decreased cellular immune response in biotin and folic acid deficiencies was partially restored to normal by administration of biotin or folic acid, respectively, shortly before immunization.

Studies on rat reticulocyte polysomes during in vitro maturation.

Abstract The polysomes of reticulocytes undergo a progressive breakdown during in vitro incubation of the cells. The breakdown was approximately 30% after 5 hours incubation, 75% after 10 hours, and 92% after 18 hours. The addition of actinomycin to the in vitro maturation system does not change the pattern of polysome breakdown and does not produce inhibition of incorporation of l -leucine-C 14 into polypeptide chains initiated on polyribosomes or into soluble protein. In contrast, lead acetate (5.7 × 10 −5 M ) added to the maturation system caused a 40% breakdown of polysomes in 1 hour and a 72% breakdown in 5 hours. There was inhibition of incorporation of l -leucine-C 14 into polypeptide chains initiated on polysomes and into soluble proteins. The presence of puromycin (2.52 × 10 −4 M ) in the maturation system produced rapid breakdown of polysomes and an almost total inhibition of incorporation of l -leucine-C 14 into proteins. Cycloheximide (8.46 × 10 −4 M ) produced a 46% breakdown of polysomes in 1 hour and almost complete inhibition of incorporation of labeled amino acids into polypeptides.

Effect of Ribonucleic Acid Extracts upon Viability of Skin Homografts in the Rat.

Summary Administration of an RNA extract prepared from the microsomal fraction of splenic cells increased the viability of skin homografts. RNA derived from a normal, adult rat which later served as the skin donor was administered to a pyridoxine-deficient rat of another strain. Skin homografting was performed after the RNA-treated recipient had received intensive therapy with pyridoxine.

Induction of tolerance to skin homografts by administering splenic cells to pyridoxine-deficient mice.

Summary 1. Tolerance of CBA/J mice to skin grafts from C3H/HeJ mice has been achieved by injection of C3H/HeJ splenic cells into pyridoxine-deficient CBA/J recipients. Skin grafting was performed subsequent to pyridoxine therapy. 2. Splenic cells obtained from A/HeJ cells were ineffective under otherwise identical conditions. 3. Grafts of tolerant CBA/J mice were rejected following injection with syngeneic cells sensitized to C3H/HeJ skin.

Effect of pyridoxine deficiency on the induction of immune tolerance in mice.

Summary A very high degree of immune tolerance of C57B1/6J female mice to skin grafts from C57B1/6J male mice has been achieved by injection of splenic cells derived from skin donors into prospective recipients while they are in a state of pyridoxine deficiency. Equal numbers of splenic cells are much less effective in the production of immune tolerance when injected into control animals than when administered to pyridoxine-deficient recipients.

Hyperreactivity to endotoxin in BCG-treated guinea pigs and its relationship to delayed hypersensitivity.

Summary The development of systemic and cellular reactivity to PPD has an entirely different pattern from that of hyperreactivity to endotoxin in BCG immunized guinea pigs. Hyperreactivity appears not to be related to altered cellular reactivity in contrast to PPD sensitivity or delayed sensitivity to well characterized proteins.

Protein synthesis in liver of pantothenic acid-deficient rats.

Summary The in vivo incorporation of 14C-amino acids into circulating serum albumin was diminished in pantothenic acid-deficient rats. However, this deficiency induced no detectable changes in the liver polysomal profiles or the activities of the liver microsomal and soluble supernatant fractions in in vitro protein synthesis. In preliminary studies, indications were obtained that the intracellular transport of newly synthesized proteins was impaired in liver cells from pantothenic acid-deficient rats.

Proteolytic enzyme system of skin. VI. Enzyme patterns in various animal species.

Summary Fresh skin extracts of various animals have been surveyed for ability to hydrolyze N-acetyl-l-tyrosine ethyl ester, l-tyrosine ethyl ester, l-phenylalanine ethyl ester, and casein. The data obtained have been interpreted in terms of conformity to results previously obtained with extracts of rat skin acetone powder.