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Effect of moderate exercise on proliferative responses of peripheral blood mononuclear cells.

We studied the effects of 30 minutes of exercise on T lymphocyte counts and proliferative responses of peripheral blood mononuclear cells (PBMC) in 25 runners. Exercise resulted in a T lymphocytosis in the immediate post-exercise period in all subjects (p < 0.001), and reduced CD4+/CD8+ ratios in 22/25 subjects (p = 0.001). The change was due primarily to a 2.2-fold increase in CD8+ cells (p < 0.001). Exercise also reduced PBMC mitogenic responses to phytohemagglutinin (PHA) in 13/14 subjects (p = 0.049), and to pokeweed mitogen (PWM) in 11/14 subjects (p = 0.022), but not to concanavalin A. Postrun sera from 5 of 6 subjects inhibited PHA but not PWM responses of resting autologous PBMC with normal CD4+/CD8+ ratios (p < or = 0.05): indomethacin and monocyte depletion blocked the serum inhibition (p = 0.003, p = 0.0006, respectively). We conclude that post-exercise suppression of mitogenic responses to PHA is due to the release of a serum factor(s) capable of inducing prostaglandin synthesis by circulating monocytes, whereas exercise-induced suppression of PWM responses depends primarily on the reversal of CD4+/CD8+ ratios.

Adult↗

Evoked responses from peripheral stimulation of the facial nerve.

Evoked responses to electrical stimulation of the facial nerve were recorded in dogs with vertex electrodes placed both inside and outside the skull. Three waveforms were recorded. The first two waveforms appeared to be related to electrical activity carried by antidromic propagation within fibers of the facial nerve. The third waveform appeared to be caused by the muscular response that occurred as a result of orthograde conduction in the nerve. The effects of changing the stimulation site, voltage, duration, and frequency were recorded. It appears that, by means of far-field techniques, it is possible to reliably record evoked responses that reflect antigrade conduction via fibers of the facial nerve.

Animals↗

Peripheral circulatory response in cardiac failure.

Derangements of the peripheral circulation play a major role in the pathophysiology of congestive heart failure. Their appearance coincides with that of the symptoms and signs that characterize the full-blown clinical syndrome. Long-term therapy with ACE inhibitors partially reverses these abnormalities, but the pathologic mechanisms are still poorly understood.

Adaptation, Physiological↗

Limited infiltration of exogenous dendritic cells and naive T cells restricts immune responses in peripheral lymph nodes.

Primary CD8 T cell responses in lymph nodes (LN) and protective immunological tumor control are quantitatively limited following immunization with exogenous peptide-pulsed dendritic cells (DC). This arises from two constraints. First, LN are saturated by relatively small quantities of exogenous DC. Second, circulation of new naive T cells into DC-infiltrated LN during the functional lifespan of the DC is negligible. Limits on DC and T cellularity in, and flux through, LN constrain the magnitude of both primary and subsequent recall responses. Enhanced immune responses and tumor control can be achieved using maneuvers to augment LN retention of DC or availability of naive T cells to Ag-presenting DC. These data offer an increased understanding of LN function in general and provide a practical basis for improvements in tumor immunotherapy.

Animals↗

Myeloid C3 determines induction of humoral responses to peripheral herpes simplex virus infection.

The complement system, in addition to its role in innate immunity, is an important regulator of the B cell response. Complement exists predominantly in the circulation and although the primary source is hepatic, multiple additional cellular sources have been described that can contribute substantially to the complement pool. To date, however, complement produced by these secondary sources has been deemed redundant to that secreted by the liver. In contrast, using a bone marrow chimeric model, we observed that C3 synthesis by myeloid cells, a relatively minor source of complement, provided a critical function during the induction of humoral responses to peripheral HSV infection. Anti-viral Ab, as generated in an efficient humoral response, has been associated with protection from severe consequences of HSV dissemination. This report offers insight into the generation of the adaptive immune response in the periphery and describes a unique role for a nonhepatic complement source.

Animals↗

Cell-mediated immunity to cytomegalovirus (CMV) and herpes simplex virus (HSV) antigens in the acquired immune deficiency syndrome: interleukin-1 and interleukin-2 modify in vitro responses.

Peripheral blood lymphocytes (PBL) were obtained from five patients with the acquired immune deficiency syndrome (AIDS), six homosexual males with lymphadenopathy, and five normal heterosexual controls. Modulation of virus-specific immunity was assayed in vitro by measuring the lymphocyte blastogenic response and the production of lymphokine (leukocyte inhibition factor; LIF) by PBL stimulated with herpes simplex virus (HSV) or cytomegalovirus (CMV) antigens in the presence or absence of interleukin-1 (IL-1) and interleukin-2 (IL-2). PBL from the control and lymphadenopathy subjects responded to both antigens in the lymphocyte transformation assay (LT) measured on day 7, and the responses were significantly enhanced in cultures grown in the presence of antigen and IL-2 (1 U/ml). PBL from the AIDS patients were unresponsive, but responsiveness was restored by the addition of IL-2. The addition of IL-1 (0.02 micrograms/ml) to antigen-stimulated PBL cultures failed to enhance the proliferative responses in all three study groups. LIF production was assayed in the supernatants from day 1 PBL cultures. LIF was not produced by PBL from AIDS patients grown in the presence of viral antigens, whereas three of five patients from the lymphadenopathy group, and three of five control subjects gave rise to positive responses. The addition of IL-1 to the antigen-stimulated cultures enhanced LIF production in the control and lymphadenopathy groups but not in the AIDS patients. The addition of IL-2 did not modulate LIF production by antigen-stimulated PBL from the control or AIDS patients while suppressing the LIF response of the similarly stimulated PBL from the lymphadenopathy patients.

Acquired Immunodeficiency Syndrome↗

Decreased chemiluminescent associated phagocytic response of peripheral blood mononuclear cells to Chlamydia trachomatis in patients with HLA-B27+ anterior uveitis.

The chemiluminescent (CL) associated phagocytic response of peripheral blood monocytes to two serovars of Chlamydia trachomatis, Shigella flexneri and zymosan was assessed in a group of 26 patients with anterior uveitis (AU). HLA-B27+ patients with AU, when compared to HLA-B27- patients with AU and appropriate controls, had a significantly decreased CL response to C. trachomatis but no difference between groups in the response to S. flexneri and zymosan. The decreased chemiluminescent (phagocytic) response of mononuclear phagocytes to Chlamydiae may indicate an important abnormality in the pathogenesis of HLA-B27+ AU.

Adolescent↗

Modulation of host immune responses by Fasciola hepatica: responses by peripheral lymphocytes to mitogens during liver fluke infections of sheep.

Fasciola hepatica infections of lambs (250 or 500 metacercariae) were shown to alter the proliferative responses of peripheral blood lymphocytes (whole blood culture) to mitogens at specific times postinfection (PI). Responses to concanavalin A (Con A) were significantly suppressed at weeks 4, 8, 10, and 11 PI whereas suppressed responses to phytohemagglutinin (PHA) occurred at weeks 4, 10, 11, and 16 PI. Only on weeks 4 and 6 PI were responses to pokeweed mitogen (PWM) suppressed. The fluke-induced modulation of responses appeared to be related more to specific phases of infection rather than to worm burdens.

Animals↗

Indomethacin sensitive suppressor cells in Crohn's disease: a possible role in decreased lymphocyte responsiveness.

Peripheral blood mononuclear cells from 18 patients with Crohn's disease were assayed for the activity of indomethacin-sensitive suppressor monocytes. This activity was found to be significantly increased when compared with 16 healthy controls. Patients were also found to have decreased lymphocyte responses to PHA and this impairment correlated with the increased suppression. In contrast, the short-lived suppressor cell activity analyzed simultaneously was found to be decreased as reported in previous studies. Thus, distinct suppressor systems may be differently affected in Crohn's disease and such immunoregulatory aberrations may explain some of the immunological alterations previously reported in Crohn's disease.

Adult↗

Inhibition of the blastogenic response of peripheral blood mononuclear cells to mitogen and antigens by bovine pulmonary macrophages and their culture supernatants.

Bovine pulmonary macrophages were shown to inhibit blastogenic response of peripheral blood mononuclear cells to high and low level stimulation with phytohaemagglutinin P. The blastogenic response of cells from calves sensitised to Pasteurella haemolytica or BCG, when stimulated with the corresponding antigen, was also suppressed by the addition of autologous pulmonary macrophages. Twenty-four-hour-old macrophage culture medium was likewise inhibitory to the blastogenic response. Determination of the arginine content of culture medium before and after 24 and 48 hours' incubation with macrophages showed a progressive decrease in arginine content. Dilution of the arginine deficient medium 1:16 with fresh culture medium did not reverse the inhibition, thus making arginine deficiency unlikely to account for the inhibition.

Animals↗

[Retuning of segmental responses to peripheral stimulation during fictive locomotion in cats].

Segmental reflex responses of the lumbosacral spinal cord to peripheral afferent stimulation were investigated in immobilized decorticated cats before and during fictitious locomotion. Appearance of fictitious locomotion was accompanied by an increase of the N1 component of the dorsal cord potential and of the dorsal root potential. Modulation of these responses depending on the phase of fictitious locomotion was observed against a background of their tonic increase. The N1 component and dorsal root potential had larger amplitudes when they appear at the end of the "extensor" phase and at the beginning of the "flexor" phase and smaller amplitudes when they were evoked at the end of the "flexor" phase and at the beginning of the "extensor" phase. Poly- and monosynaptic reflex responses of motoneurons revealed the same phase dependence during fictitious locomotion. Mechanisms and physiological significance of the revealed retuning of segmental reflex responses are discussed on the basis of the obtained data.

Animals↗

Influence of local sensory afference in the calibration of human balance responses.

Peripheral sensory modulation of balance behavior may require a "calibrated" mechanism which would maintain upright standing by a feedback control of torque at the ankle joint. The calibration of human balance was studied using a systematic presentation of perturbation excursions and velocities in normal freely standing subjects. All perturbations (posterior movements of a force platform) induced a forward body sway and were presented by first increasing and then decreasing the magnitude of perturbation. In preselected conditions the stability of the ankle and hence the accuracy of surface orientation inputs was altered using a foam base placed under the subjects feet. Each subject pressed a hand held response key at the moment a postural disturbance was detected. The automatic neuromuscular response (ANR) was recorded from the gastrocnemius muscles bilaterally and the perturbation detection time (DT) was obtained from the onset of thenar muscle discharge. The major findings in this study were: (1) Conscious DT changed as a function of step variations in perturbation excursion and was disassociated from the ANR latency. The ANR latency remained essentially constant in all conditions and did not have any influence on the kinematics of body sway. (2) Normalized peak body sway decreased during unstable ankle conditions and the reduction of body sway could be attributed to an increase in the gain of the ANR across a 200 ms integration period. The ANR 200 ms amplitude also showed higher correlations with perturbation magnitude during unstable (versus stable) ankle conditions. (3) The 200 ms gastrocnemius amplitude was modulated by excursion and velocity of platform displacement but the amplitude integrated over 100 ms was dependent on only the velocity of perturbation. Our results indicate that balance is controlled by a centrally initiated postural response but regulated in amplitude by local sensory information. These results establish that the gain of the ANR is functional, peripherally driven, and occurs subconsciously to alter the kinematics of body sway.

Adult↗

Mitogenic response of peripheral blood lymphocytes from patients with Graves' disease incubated with solubilized thyroid cell membranes containing TSH receptor and with thyroglobulin.

Transformation of peripheral blood lymphocytes (PBL) in response to solubilized TSH receptor and to human thyroglobulin (hTG) was carried out in patients with Graves' disease (GD). Mean stimulation index (SI) in response to solubilized TSH receptor was significantly increased only in hyperthyroid GD patients (SI = 3.0 +/- 1.8 SD, n = 13, p less than 0.025) when compared to normal subjects (SI = 1.5 +/- 0.8 SD,n = 14). All other subgroups of GD patients (i.e., euthyroid GD patients after treatment as well as those with/without ophthalmopathy or TSH-displacing antibody [TDA]) showed a tendency to elevated mean SI, which, however, was never significantly increased. In contrast, patients who were suspected of having a "disseminated autonomy" showed a tendency to decreased mean SI compared to GD patients. The mitogenic response of PBLs induced by solubilized TSH receptor could be suppressed by incubation of antigen and PBLs with bTSH. Control experiments with purified protein derivate of tuberculin(PPD) as stimulating antigen revealed, however, that bTSH itself suppresses the mitogenic response of PBLs and that the decrease of SI in this experiment is not due to blockage of the antigenic determinants of the TSH receptor protein. Human thyroglobulin (hTG) produced no significant increase in the SI of PBLs. Only 9 out of 47 GD patients showed an SI higher than the mean of normals + 2 SD. All those patients, however, who showed an elevated SI ( greater than 2.0) also revealed an increased SI with solubilized TSH receptor.

Cell Membrane↗

Interleukin-2 activity and the response of peripheral blood lymphocytes in patients with gynecologic malignancies.

The interleukin-2 (IL-2) production in peripheral blood lymphocytes (PBL), the response to IL-2, and the IL-2 absorption by PBL was studied in 34 patients with gynecologic malignancies. In addition measurement of the OKT 4/8 cell ratios were made. The OKT 4/8 cell ratio in patients with advanced gynecologic malignancies was significantly lower than that in patients with benign tumor. PBL from advanced cancer patients activated by phytohemagglutinin (PHA) had significantly lower IL-2 productivity than that from patients with benign tumors, while no significant difference was observed in its abilities to respond to IL-2 and to absorb IL-2. The OKT 4/8 cell ratio and IL-2 productivity in PBL of patients with good prognosis were significantly elevated after chemotherapy. On the other hand, PBL of patients with poor prognosis declined to about one-half of the preoperative levels. Although in patients with good prognosis the ability of PBL to respond to IL-2 was not changed before and after treatment, in patients with poor prognosis the response was significantly increased after chemotherapy. However, the ability to absorb IL-2 was not affected by treatment.

Antigens, Surface↗

Nonspecific immune response of peripheral blood neutrophils in two horse breeds (Anglo-Arabian and Spanish-Arabian): response to exercise.

The aim of the present paper was: (1) to find out if there were any differences in the nonspecific immunological pattern of peripheral blood neutrophil between two breeds of horses (AA and SA); (2) to evaluate the effects of an exercise in the aerobic-anaerobic threshold. This has been observed in a group of 11 untrained horses (6 SA and 5 AA) of 2.5 years old. No statistically significant differences were found in the different stages of immune response between the rest and immediately after physical exercise to two breeds. However, the chemotaxis was significant higher at rest in the AA than SA breed. A positive correlation was found at rest between the phagocytic and oxidative metabolism activity for AA breed and a negative correlation too between the adherence and chemotaxis with phagocytic capacity, immediately after exercise test, for the same breed.

Animals↗

Responses of peripheral auditory neurons to two-tone stimuli during development: II. Factors related to neural responsiveness.

In an accompanying paper (Fitzakerley et al., 1994), it was demonstrated that there is a significant developmental correlation between the appearance of tuning and two-tone suppression. However, it was also found that some sharply tuned neurons meeting minimal adult standards did not exhibit suppression. Therefore, in order to investigate other factors that may be related to the demonstration of suppression in peripheral auditory neurons, the relationship of two-tone suppression with various parameters related to neural responsiveness was studied in perinatal kittens. A positive correlation was made between the observance of suppression and driven discharge rate, characteristic frequency (CF), and threshold, all properties which change significantly during the final stages of cochlear differentiation. In older animals, suppression was also observed in higher percentages of neurons having low spontaneous rates (< 1 spk/s). Suppression was evoked less often by test tones placed below CF than above CF in neurons recorded from younger animals, and was generally produced by a narrower range of test tone intensities than those recorded from adults. As a result, the conventional description of suppression as observed in peripheral auditory neurons in mature animals must be extended to include these factors when responses of immature neurons are considered.

Acoustic Stimulation↗

Beyond 51Cr release: New methods for assessing HIV-1-specific CD8+ T cell responses in peripheral blood and mucosal tissues.

Much scientific effort has been directed towards elucidating the complexities of cell-mediated immune responses to HIV-1(reviewed in [1,2]). These studies have attempted to explain the immune system's ultimate failure to contain viral replication, leading to development of AIDS disease, and to identify immune responses that will be useful in developing immunomodulatory therapies and novel vaccine strategies. Although many of the complex interactions involved in AIDS pathogenesis remain unsolved, great progress has been made in characterizing the kinetics, specificity and functional dynamics of HIV-1-specific T cell responses. These investigations have come at a time when advances in virology, cellular immunology and molecular biology have converged to provide a variety of methodological approaches not available at the onset of the AIDS pandemic. Application of these tools to other infectious diseases and immunopathological conditions will provide a fertile area of research for future years. This review focuses on recent developments in the assessment of HIV-1-specific T cell responses in peripheral blood and tissues, with a particular emphasis on flow cytometry-based approaches.

Animals↗

The biological relevance of polykaryons in the immune response.

Peripheral blood monocyte-derived multinucleated giant cells are a well-known feature of chronic inflammatory conditions. Similarly, virus-induced syncytia derived from CD4+ cells are considered to be typical of human immunodeficiency virus infection under culture conditions. Here, Stefano Fais and colleagues summarize recent experimental results comparing the mechanisms underlying the formation and fate of these two different polykaryons, discussing their putative role in the immune response.

CD4-Positive T-Lymphocytes↗