Leon T. Rosenberg

Prolonged effect of psychological disturbance on macrophage chemiluminescence in the squirrel monkey

The following study assessed changes in macrophage responsiveness after a 24-h period of psychological disturbance in mother and infant squirrel monkeys. Utilizing a luminol-dependent assay, an 80-min chemiluminescent burst was measured in blood monocytes in response to zymosan stimulation. Cells obtained from stressed mothers and infants showed significant increases in chemiluminescence (CL) as compared to baseline levels. Moreover, the elevated pattern of response persisted for at least 2 weeks after the mothers and infants were reunited. The initial change in CL was associated with increased pituitary-adrenal activity and leukocyte redistribution, but these measures returned to normal levels following reunion. Thus, this study has demonstrated a prolonged change in an immune parameter following a transient alteration in the psycho-endocrine status of the host.

Effect of Maternal Separation on the Complement System and Antibody Responses in Infant Primates

Hemolytic complement activity and complement protein levels were evaluated before and after psychological disturbance in the squirrel monkey. Significant increases in hemolytic complement activity were observed following separation of 6-month-old infants from their mothers. Complement protein levels were generally correlated with hemolytic activity, but did not show the same pattern of change. C3 levels did not change consistently after maternal separation, while C4 decreased significantly on Day 7, and then began to return toward basal levels by Day 14. The alterations in complement activity were associated with elevated adrenal hormone secretion, but were not directly correlated with plasma cortisol levels. A second experiment showed that increased hemolytic complement activity also occurred in juvenile squirrel monkeys following 4-hour to 7-day removals from a peer group. The effect of maternal separation on antibody responses to viral challenge was evaluated in a third experiment. Separated infant squirrel monkeys mounted a smaller antibody response than did control infants that remained with their mothers. A similar decline in antibody responses was observed in separated rhesus macaque infants, but the effect was less marked in this species. Thus, the strong effect of psychological disturbance on immunity in the squirrel monkey is probably related to its prolonged endocrine responses.

HLA and mate selection

HLA types of the partners in 1017 couples were determined. It appeared that there was statistically significant occurrence of like types more frequently than predicted by chance. The existence of ethnic or racial groups with characteristically different frequencies of the HLA types might explain the result.

Physiological Consequences of Maternal Separation and Loss in the Squirrel Monkey

As the chapters in this volume indicate, the squirrel monkey has been a valuable subject in many areas of research. One area in which the squirrel monkey has been particularly popular is in the investigation of developmental issues. Our laboratory has found it to be the subject of choice for two reasons. First, the specificity and duration of the emotional bond between mother and infant make the squirrel monkey a good model for the study of attachment processes. Second, the resiliency of the infant and its high adrenocortical hormone levels are extremely conducive to experiments on the effects of psychological and environmental perturbations that occur early in life. Here we will review a series of studies on the physiological consequences of maternal separation in infant squirrel monkeys, and also discuss some of the factors that can ameliorate the deleterious hormonal and immunological effects of maternal loss.

Rapid release of Iron from Ferritin by Siderophores

The ability of the microbial siderophores deferriferrichrome, deferriferrichrome A, and enterobactin to remove iron from ferritin has been investigated. In contrast to previously published data with other chelators, all three siderophores rapidly released iron from the mammalian storage protein. Enterobactin was found most efficient at removing ferritin-bound iron. Using this siderophore, the mechanism by which ferritin sequesters iron was studied. The relative iron saturation level of ferritin influenced the rate of chelation by the microbial siderophores.

Contribution of tryptophan to the biologic properties of anti-dinitrophenyl antibody☆

Abstract Labeling of a few trytophan residues with 2-OH-5-NO 2 benzylbromide decreases the complement fixing and sensitizing capacity of anti-dinitrophenyl antibody, leaving the antibody combining site unaffected. This suggests a role for a trytophan containing peptide in the affected activities.

Acquisition of iron from transferrin bySalmonella paratyphi B

The ability ofSalmonella paratyphi B to obtain iron from human, bovine, and rabbit transferrin was studied. All three transferrins restored the growth potential for otherwise ironstarvedS paratyphi B producing enterobactin. No exogenous siderophore was needed for growth to occur. A non-enterobactin-producing derivative ofS. paratyphi B was unable to acquire iron from transferrin, and transferrin did not restore the growth potential of the organism. Sequestering the transferrin fromS. paratyphi B in dialysis tubing did not affect the ability of the transferrin to supply iron to the organism.

Passive Cutaneous Anaphylaxis with Antigen-Antibody Complexes and Additional Antigen.

Summary Small amounts of antibody and excess antigen sensitize guinea pig skin so that challenge with intravenous antigen and dye elicits passive cutaneous anaphylaxis. The significance of the biological reactivity of antigen-antibody complexes is briefly discussed.

Mutation in Salmonella typhimurium recovered from livers and spleens of mice

Balb/c mice were inoculated intraperitoneally with TA2662, a smooth derivative of the Salmonella typhimurium Ames tester strain (TA102) which carries the mutable hisG locus on a multicopy plasmid, or TA103, which carries the same hisG gene on the chromosome. The bacteria were recovered at various times from the livers and spleens of the infected mice. Total numbers of bacteria were determined and the mutant frequency was estimated. The frequency of occurrence of histidine prototrophs in experiments using TA2662 was substantially above the frequency found with this strain grown in vitro. The mutant frequencies in experiments using TA103 recovered from mice were also highly significantly increased above background. We did not identify factors which might suggest selection in vivo for histidine prototrophs. There is sufficient histidine in body fluids of the host for the growth of His- bacteria. The His- and His+ derivatives were found to grow equally well in vitro in the presence of amounts of histidine approximating concentrations known to exist in vivo. It is probable that mutations in TA2662 are greatly underestimated, since the hisG-containing plasmid is lost at relatively high frequency during incubation in a variety of conditions.

The role of tolerance in the lack of cross-reactivity between homologous (structurally related) proteins: Cross-reactions between α-lactalbumins and between lysozymes recognized by antibodies from intolerant rabbits

Abstract The carrier-effect was used in an attempt to break tolerance while raising antibodies to guinea pig α-lactalbumin and mouse lysozyme. A portion of the antibody to guinea pig α-lactalbumin cross-reacted with the auto-antigen, rabbit α-lactalbumin. Nevertheless, no cross-reaction between native lysozyme and lactalbumin could be shown although significant cross-reactions between different lactalbumins and between different lysozymes were demonstrated. The data suggest that tolerance to homologous sequences of globular proteins is an important factor hindering the detection of cross-reacting haptens despite conformational similarity.