Foreign Red Blood Cells Research Articles

Immunomodulation by gadolinium chloride-induced Kupffer cell phagocytosis blockade

Gadolinium chloride (GdCl3), a rare earth metal salt, depresses macrophage activity, and is commonly used to study the physiology of the reticuloendothelial system. In the present work, the effect of GdCl3-induced Kupffer cell blockade on the humoral immune response in mice to sheep red blood cells (SRBC) was investigated. Kupffer cell phagocytosis blockade was found to increase both the primary and secondary immune responses to SRBC. The primary immune response was significantly augmented in animals injected intravenously with GdCl3 2, 3 or 4days before injection of the cellular antigen, but GdCl3 injected 7days before the antigen did not modify the immune response. Increased secondary humoral immune responses were also observed. When GdCl3 was injected 2days before the second dose of antigen, the numbers of both IgM and IgG-producing plaque forming cells were augmented. GdCl3 injected 2days before the first dose of SRBC did not modify the humoral immune response. Earlier studies with 51Cr-labelled foreign red blood cells suggested that the augmentation of the humoral immune response in GdCl3-pretreated mice is a consequence of the spillover of the antigen from the liver into the spleen and other extrahepatic reticuloendothelial organs.

Effects of chronic exposure to sublethal concentrations of lead acetate on heme synthesis and immune function in red-tailed hawks

Red-tailed hawks were exposed to sublethal levels of lead acetate for periods of 3 or 11 weeks. Alterations in the heme biosynthetic pathway were demonstrated after the first week of exposure to 0.82 mg lead per kilogram body weight per day. Activity of erythrocyte porphobilinogen synthase (aminolevulinic acid dehydratase) was depressed significantly and did not return to normal levels until 5 weeks after the termination of lead treatments. A rapid and relatively brief increase in erythrocyte free protoporphyrin and a slower but more prolonged increase in its zinc complex were also demonstrated with exposure to this dose of lead for 3 weeks. Less substantial decreases in hematocrit and hemoglobin levels occurred but only in the longer experiment with exposure to higher lead levels. Short term, low level lead exposure did not effect immune function significantly in the hawks, as measured by antibody titers to foreign red blood cells or by the mitogenic stimulation of T-lymphocytes. Increased lead exposure produced a significant decrease in the mitogenic response but had no effect on antibody titers.

The influence of a novel glucocorticoid antagonist on endotoxin lethality in mice strains

Ru 38486 is a recently synthesized molecule which has little intrinsic agonist or antagonist activity but which is specifically capable of antagonizing selected glucocorticoid-induced processes such as liver enzyme induction and gluconeogenesis. This material sensitized both the Swiss albino OF1 and the refractory C3H/HeJ strain of mice to endotoxin lethality and impaired the protective effect of dexamethasone under these conditions. The effect of Ru 38486 and endotoxin was not additive on liver tryptophan pyrrolase and tyrosine transaminase but hepatic glycogen depletion was significantly greater than both agents were given as compared to either of them alone. Ru 38486 was without effect on the activity of the reticuloendothelial system as evidenced by both the clearance of carbon and the distribution of foreign red blood cells. In doses that protected OF1 mice against Ru 38486-mediated sensitization to endotoxin lethality, liver enzyme and glycogen levels were still below normal, albeit significantly greater than in animals succumbing to the toxin. These results constitute the first evidence that a drug acting specifically at the level of the glucocorticoid receptor can modulate the course of endotoxicosis.

The primary immune response in mice. 3. Retention of sheep red blood cell immunogens by the spleen and liver.

The antibody-inducing activities of foreign red blood cell immunogens sequestered in the spleens and livers of mice injected with sheep erythrocytes were evaluated during the early periods of the immune response. Estimates of immunogenicity, obtained from the magnitudes of anti-sheep red blood cell hemolysin responses evoked in sensitized recipient mice by subcellular tissue fractions prepared from these phagocytic organs, showed that the liver and spleen differ greatly in their handling of this particulate antigen. The liver, functioning primarily as a scavenger organ, destroys completely the immunogenicity of the heterologous erythrocytes in 12 hr. In contrast, the spleen handles foreign erythrocyte immunogens in at least two different ways: approximately 90% of the initially sequestered activity is rapidly destroyed by the spleen in 6 hr, but the remaining activity, associated chiefly with a tissue fraction possessing the sedimentation properties of "light mitochondria," is retained at a significant level for 3 days, and then progressively decreases to a low level until the 7th day. A correlation of the observed changes in the properties of the immunogenic tissue fraction with known cellular events in the spleen stimulated by antigens indicates that the retention of the degradable erythrocyte immunogen is essential for stimulating and maintaining immune reactions in this antibody-producing organ.

Untersuchungen zum Ablauf der Phagozytose in der Peritonealflüssigkeit der Ratte

Phagocytic activity of mononuclear cells of the rat peritoneal fluid has been investigated at different times, after the addition of foreign red blood cells (sheep and chicken red blood cells). The mononuclear cells phagocytized both types of erythrocytes, but preferentially chicken red blood cells. To a lesser extent the neutrophilic granulocytes phagocytized chicken red blood cells. The investigations showed that in all instances a number of the mononuclear cells exhibited no phagocytic activity even in the presence of free foreign red blood cells.

Specific tolerance to sheep erythrocytes in mouse bone marrow cells.

RECENT experiments indicate that cells of at least two kinds can cooperate in the antibody response of mice to foreign red blood cells. Thymus and bone marrow cells confer significant antibody responsiveness on lethally irradiated mice when injected together, but not separately1, and it seems probable that it is the bone marrow, and not the thymus, cells that make the antibody2. There is no evidence, however, as to which population dictates the specificity of the response. The discovery that mice can be made specifically hypo-responsive “tolerant”) to sheep red blood cells3 means that this point can be tested.

The immune response to foreign red blood cells and the participation of short-lived lymphocytes.

The sequence of morphological changes in the rat spleen following SRBC injection associated with hemolysin production has been correlated with estimates of proliferative activity by splenic lymphatic tissue. Formation of new, reactive germinal centers containing macrophages which engulf nuclear debris is a prominent feature of the response. This is prevented by pretreatment of the animal with cortisol. Indirect evidence is provided that short-lived lymphocytes produced in germinal centers may be a necessary component in the induction of other cells to proliferate and differentiate into hemolysin-producing cells. The reasons are discussed for considering short-lived lymphocytes, such as those produced in the thymus, bone marrow, and germinal centers, as differing from long-lived lymphocytes capable of antibody synthesis.

Suppression of antibody production by phytohaemagglutinin.

THE in vitro effect of phytohaemagglutinin (PHA) on small lymphocytes from the peripheral blood is now well known1,2, and a limited number of studies of the effect of this substance in vivo have been made in man3,4 and laboratory rodents5–7. Calne and his colleagues8 reported the use of PHA to augment the immunosuppressive effect of ‘Imuran’. We have studied the effect of PHA on the immune response of rats to foreign red blood cells, and the preliminary results of our experiments are reported here.

Haemolytic properties of immune chicken antibody.

IN the course of a study of immunological responsiveness of chickens to foreign red blood cells our interest was attracted by the observed discrepancy between high agglutination titres of immune chicken sera and their inability to show lytic properties in the presence of complement. It is well known that different antibody–antigen systems exhibit different abilities to fix guinea pig complement when mammals are used as antibody producers1. The failure of immune bird sera to show a significant complement-fixing activity was mentioned by Meyer2 and by Rice3 in birds infected with ornithosis virus and S. pullorum. It was postulated that avian antibody formed with antigen non-complement-fixing aggregates4, and that avian antibody lacked some character that was important for combining with complement5. This problem, however, was not further explored, and all available data were based on the experiments made with guinea pig complement. It seemed, therefore, reasonable to investigate in a preliminary way whether or not chicken antibody haemolyses red cells in the presence of complement from different animal species.

Phagocytosis of foreign red blood cells by the reticulo-endothelial system.

The clearance rate of nucleated pigeon erythrocytes injected intravenously into mice and rats has been calculated either by routine differential red cell counts or by measuring the radioactivity of the erythrocytes tagged with P32. Histological evidence is given that the foreign erythrocytes are phagocytized by the reticulo-endothelial cells of the liver and spleen. The clearance rate of the foreign erythrocytes, which measures the speed of the phagocytosis, follows in mice a regular exponential function similar to this previously established for other colloids. No spontaneous antibodies to pigeon erythrocytes could be detected in mice. The rapid and complex clearance rate of pigeon erythrocytes observed in rats is related to the existence of spontaneous specific antibodies. The simultaneous injection of pigeon erythrocytes and of India ink into mice, both phagocytized by the RE cells, results in a competition between the two substances in favor of the smaller particles of carbon.

Tolerance phenomena in birds.

On this occasion I should like to speak about some of the recent research which has been carried out at our laboratory in Prague. We have continued our work on the immunological effects of embryonic parabiosis in birds and have made new analyses of the phenomenon of immunological tolerance. In our earlier work, when studying the after-effects of embryonic parabiosis between birds of the same species, we observed a complete suppression of agglutinin formation (Hašek 1953). Later we confirmed the results of Billingham, Brent & Medawar (1953) by showing that embryonic parabiosis causes tolerance of skin homografts (Hašek 1954). Embryonic parabiosis brings about an immunological tolerance which persists for a long time, sometimes perhaps throughout the individual’s life. Persistence of immunological tolerance has sometimes been observed even in birds 2 to 3 years of age. Billingham et al . (1956) described the occurrence of persistent blood chimerism after experimental embryonic parabiosis in chickens, an observation similar to that made earlier by Owen (1945) in his study of natural parabionts of cattle. I should first like to draw your attention to our results concerning the persistence of heterologous erythrocytes, and the occurrence of interspecific blood chimeras, after embryonic parabiosis between members of different species. By the 2nd or 3rd week after hatching, foreign red blood cells had already disappeared from the circulation of ducks which had been in parabiosis with hens and of hens which had been in parabiosis with ducks. The same result was obtained in the hen-guinea-fowl and hen-pheasant parabionts.

Der Einfluß künstlicher Durchströmung auf den postmortalen Schwund der Cochlearpotentiale

The influence of various perfusing fluids on the cochlear potentials has been proved in 11 experiments on guinea-pigs. Foreign blood or red blood cells in Ringer's solution increased the magnitude of thepost mortem reduced electrical response. The increase started immediately with the beginning of the perfusion. The degree of the increase depended upon the oxygen content of the perfusing fluid. A solution of oxyhaemoglobin caused an inhibition of the postmortal reduction, but did not increase the potentials. Ringer's solution had no influence.