Eric L. Nelson

IRRADIATION, IMMUNIZATION, AND SENSITIVITY TO TOXIC SUBSTANCES: CONSIDERATIONS IN A CONCEPT OF CELLULAR IMMUNITY

The idea that cells, by virtue of their structure and composition, may be or become immune to particular agents has found expression in various concepts of cellular immunity. The resistance exhibited by vertebrates, invertebrates, and plants has, in many cases, been related to particular cells.’ Natural and tissue immunity are usually explained on biochemical and genetic bases. However, those individuals interested in antibodies and their formation have in some cases accounted for local resistance in terms of local antibody production.2 The pharmacologic concept of tolerance also has been ascribed to resistance of individual cells to particular drugs.8 To workers concerned with the development of bacteriophage (particularly with bacteria in the lysogenic state), cellular immunity means the resistance of a particular bacterial cell to superinfection while latently infected with phage? Recent studies with mammalian viruses in tissue culture indicate that cells may exhibit resistance to infection with a virus to which they previously had been expo~ed.~ Finally, however, there is an area of research in which the term cellular immunity has come to be best known and understood. This is the area that deals with phagocytic cells that are believed to acquire resistance or an enhanced capacity for destruction of a bacterial agent following previous exposure to it or its products. That such cells are actively involved in resistance to disease has been emphasized by recent reports of Severs and Suter7 involving quantitative transfer of resistance to tuberculosis via monocytes. Most of the work in this area has been concerned with studies of the tubercle bacillus in isolated mononuclear cells from guinea pigs and rabbits.*-12 Other studies have concentrated on the host-parasite relationship between phagocytes and B r ~ e l l a , ’ ~ J ~ fungi,16 Salmonella,ls Escherichia c01i,17 and Pseudomonas.lg A detailed and critical analysis of this latter type of cellular immunity (that is, that dealing with a bacterium and a phagocytic cell) recently has been presented by Elberg.12 It is this kind of cellular immunity with which I shall be concerned in this paper.

Serum Glycoprotein Concentrations Following Immunization in the Rabbit.

Summary The effects of primary immunization on the serum concentrations of total glycoprotein, seromucoid, γ-globulin polysaccharide, total protein, and γ-globulin protein in rabbits have been investigated. Statistically significant increases occurred in the polysaccharide and protein moieties of the γ-globulin fraction. Repeated injections of normal animals with sterile 0.85% sodium chloride subcutaneously, intravenously, and intraperitoneally were without significant effect. The results of the chemical analyses have been discussed with reference to electrophoretic studies.

A Comparison of Serum Glycoprotein Concentrations in Four Species of Mammals

TARAS, M. 1948. Photometric determination of magnesium in water with brilliant yellow. Analyt. Chem., 20:1156-58. TOBIAS, J. M. 1948a. Potassium, sodium, and water exchange in the irritable tissues and haemolymph of an omnivorous insect Periplaneta americana. Jour. Cell. and Comp. Physiol., 31:125-42. 1948b. The high potassium and low sodium in the body fluids and tissues of a phytophagous insect, the silkworm Bombyx mori, and the change before pupation. Ibid., 31:143-48.

Maintenance of globulin levels in x-irradiated rabbits after immunization.

Rabbits were injected with antigen 24 hours after x-irradiation. Antibody titers were correlated with relative changes in gamma-beta globulin levels determined electrophoretically. Irradiated, immunized rabbits did not form detectable antibodies but had significantly greater globulin levels than non-immunized, irradiated controls. This relative difference occurred at the time nonirradiated, immunized rabbits were producing primary antibody.

The isolation of unidentified pleomorphic bacteria from the blood of patients with chronic illness.

Abstract 1. 1. Unidentified pleomorphic bacteria were isolated from the blood of 44 of 100 patients with chronic illness including fevers of unknown origin, lymphomas, chronic brucellosis, cardiovascular disease, and Reiters disease. In only two instances were similar organisms isolated from so-called normal individuals. 2. 2. A number of the UPB were resistant to penicillin and a few were resistant to other antibiotics. 3. 3. The organisms are morphologically very similar to Corynebacteria and may belong to this genus. 4. 4. None of the UPB were pathogenic for laboratory animals. All, however, were pathogenic for five-day chick embryos.

Lengthened Induction Period or Immunologic Unresponsiveness Depending on Antigen Dose in Adult, X-Irradiated Rabbits.∗:

Summary Adult rabbits were injected with either 10 mg or 100 mg of bovine albumin 24 hours after 400r x-irradiation. The dose of irradiation was shown to suppress completely the antibody response to the smaller amount of antigen but not to the larger amount. In the latter case the induction period was lengthened and a delayed antibody response was determined to have occurred sometime between the 14th and 24th day after injection. Whether antibody formation was to be suppressed or delayed could be correlated with the disappearance of radioiodinated antigen from the blood and the amount of antigen remaining. It was further shown that the 10 mg dose of antigen but not the 100 mg dose established a state of immunologic unresponsiveness to a subsequent challenge with antigen.

Effect of Pseudomonas on Lactate Production by Mouse Monocytes.

Summary Mouse monocytes, induced by intraperitoneal injection of mineral oil, produced lactate from only glucose and fructose. No net lactate production was noted from 29 other sugars. In vivo infection of monocytes resulted in at least a 2-fold increase in lactate production. However, no effect was noted when either heat-killed Pseudomonas aeruginosa or sonic fractions thereof were added to monocytes in vitro. No significant differences in lactate production were noted between cells obtained from immunized and non-immunized animals.

Effect of a Pseudomonas Fraction on Oxidase Activity of Mitochondria and Monocytes.

Summary A commercially prepared polysaccharide (Piromen) from a species of Pseudomonas inhibited both succinic and cytochrome oxidases of mouse liver mitochondria in vitro. Piromen alters rate of reaction rather than completely suppressing it. Cytochrome oxidase activity seemed to be more sensitive to Piromen than succinoxidase activity. Similar studies utilizing mouse monocytes indicated that succinoxidase activity could be reduced or completely abolished, but cytochrome oxidase activity was relatively insensitive to Piromen inhibition. Inhibition of monocyte succinoxidase activity was proportional to concentration of Piromen used. The excellent technical assistance of Mr. John Meacham is gratefully acknowledged.