Cathleen Collins-Lech

NEUTROPHIL DEATH AS A DEFENCE MECHANISM AGAINST CANDIDA ALBICANS INFECTIONS

In studies of experimental Candida albicans infections, growth of invading organisms sometimes ceased before the organisms reached the neutrophil infiltrates. Lysates of human neutrophils inhibited the directed growth of candida pseudohyphae in agarose gel and suppressed the proliferation of candida yeast in broth cultures, but did not kill the organisms or prevent their germination. The growth-inhibitory material released from disrupted neutrophils had an estimated molecular weight of 30 kD and differed from most previously described neutrophil antimicrobial factors in that it was present in cell sap rather than granules, and did not appear in the supernatant after stimulation of the cells. Neutrophil death and dissolution may represent an alternative host defence mechanism against invasive C albicans infection.

Class-specific antibodies in young and aged humans against organisms producing superficial fungal infections.

Class‐specific antibodies (IgG, IgA and IgM) against Candida albicans, Pityrosporum orbiculare and Trichophyton rubrum were measured in the serum from twenty‐one young subjects (aged 23–44) and twenty elderly subjects (aged 70‐88) who did not have a history of significant superficial fungal infections. We found that (a) antibody to all three organisms was present in all subjects in both groups, (b) except for a reduced level of IgM antibody against P. orbicular, the elderly subjects demonstrated humoral responses in these assays similar to those of the young subjects, (c) IgA antibody was present in higher amounts against C. albicans than against P. orbiculare or T. rubrum in both groups, and (d) the proportion of IgM antibody against T. rubrum was higher than that against the other two organisms. These findings suggest that the ecology of these three organisms with respect to the normal human host may be reflected in the serological responses against them

Differentiation of the effects of preincubation and indomethacin on lymphocyte transformation

Abstract Lymphocyte-transformation responses of human peripheral blood mononuclear cells to a suboptimal concentration of phytohemagglutinin were found to be augmented by either 24-hr preincubation or by the addition of 1.0 μg/ml of indomethacin to the cultures. Preincubation altered the lymphocyte-transformation kinetics by accelerating the response in a manner similar to that obtained by increasing the concentration of mitogen. Indomethacin did not cause this type of effect, but did produce a fairly constant degree of enhancement throughout the period of maximal response (cultures harvested on Days 3 to 7). Indomethacin also produced enhancement of the lymphocyte transformation response to the suboptimal phytohemagglutinin concentration even when the lymphocytes were preincubated beforehand, indicating that these two maneuvers were additive. Fresh, autologous, mononuclear cells did not suppress the enhanced response of preincubated cells, indicating that, in this system, preincubation may involve changes in the responding cells themselves rather than destruction of a suppressor-cell population. Therefore, these studies indicate that a short (24-hr) preincubation and the addition of indomethacin (1.0 μg/ml) to lymphocyte cultures produce enhancement of the lymphocyte-transformation response to a suboptimal mitogen concentration through different mechanisms.

Inhibition of lymphocyte transformation responses to phytohemagglutinin by normal human plasma

Abstract Marked variability in lymphocyte transformation responses to a suboptimal phytohemagglutinin concentration (0.1 μg/ml) was observed when peripheral blood mononuclear cells of normal subjects were cultured in media containing 15% autologous plasma. Low responses were related to the plasma and were caused by direct inhibition rather than an inability to support the response. This inhibitory activity varied greatly among different plasma specimens and was also found in human and animal serum. It appeared to be specific for suboptimal concentrations of phytohemagglutinin and could be overcome by increasing the mitogen concentration. The inhibitory activity was heat stable, was not dialyzable, and appeared to affect a very early stage of the response since a delay in addition of the inhibitory plasma reversed its effect. Our interpretation of these results is that human plasmas vary greatly with respect to their ability to bind phytohemagglutinin so that the addition of different plasmas to lymphocyte cultures stimulated by a limiting concentration of phytohemagglutinin results in marked variability of the results obtained.

Kinetics of Lymphokine Production by Lymphocytes from Elderly Humans

Production in vitro of the lymphokine leukocyte migration inhibition factor (LMIF) was studied for elderly as compared to young human subjects over an 8-day period of culture. When stimulated by either the antigen streptokinase/streptodornase (SK/SD) or the mitogen concanavalin A (Con A), the peak of LMIF production was retarded in cultures of lymphocytes from elderly subjects. Absolute peak values and numbers of positive responses were diminished in this group when the cells were stimulated with SK/SD but not with Con A. However, if LMIF production during the first 48-hour period was examined, the responses to Con A were also diminished in the elderly group. Retardation of lymphokine production by lymphocytes from elderly humans may be relevant to the assessment of immunologic competence in this group as well as to potential adverse effects on in vivo reactions of cell-mediated immunity.

Effect of age on generation of progeny from antigenstimulated human lymphocytes

Numerous studies have shown the proliferative response to various mitogenic stimuli of peripheral blood lymphocytes from elderly humans to be impaired. The present investigation examined the termination phase of antigen-stimulated proliferative responses of lymphocytes from elderly and young subjects. In both groups, the responding lymphocytes appeared to stop proliferating and enter the resting stage of the cell cycle when a certain total number of progeny had been generated, suggesting the phenomenon of density-dependent regulation of growth. Lymphocytes from elderly subjects stopped proliferating when significantly fewer progeny had been generated than did those from young subjects. The data suggest, therefore, that lymphocytes from elderly humans may have increased sensitivity to one or more of the factors which cause density-dependent inhibition of growth.