Anthony C. Trakatellis

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.

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.

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.