Interaction between the brain and the immune system.
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Animals↗
Biomedical subjects
D T Lysle
Publications and source records attributed to D T Lysle.
Bidirectional interaction between the central nervous system and the immune system.
We believe that any questions regarding whether the CNS can alter immune system functions no longer remain. It can conclusively be stated that the immune system is susceptible to influences of the CNS. It remains to be determined whether all classes of lymphocytes, NK cells, macrophages, polymorphonuclear leukocytes, and other antigen-processing cells are all susceptible to CNS influences. We have presented evidence that peripheral blood lymphocytes may not reflect the immunological activity of lymphocytes within lymphatic tissue after being influenced by a stressor. Thus, all types of immunological cells must be evaluated in different organs. Whether the immune system of young and old animals respond in the same way must also be determined. The sex of the animal needs to be taken into consideration. What immune responses are important to measure? Do in vitro responses reflect the ability of an animal to resist infectious disease or susceptibility to autoimmune and malignant diseases? Certainly, absence of an immune response is detrimental to health. It must be determined whether moderately suppressed immune function in multiple compartments is as detrimental as total absence of an immune response in a single immunological compartment. The data that we have presented with respect to adjuvant arthritis indicate that an immune response in the peripheral of the animal can be modified by a stressor and influence an immunopathological process. This may indicate that the most important immune compartment to evaluate with respect to altering disease susceptibility is the peripheral blood and that lymphoid tissue may be interesting, but not clinically relevant. The reasons why the peripheral blood and lymphoid tissue differ in their immunological function following exposure to a stressor must be determined. We have reviewed information indicating that lymphoid tissue is innervated and that such innervation can modify immune function. In addition, hormones released by the CNS may alter immune function. Yet, much of this data are contradictory and whether immune enhancement or suppression occurs is not clearly defined with respect to any experimental manipulation involving denervation or the addition of hormones to in vitro cultures. Whether this reflects the age of the experimental animal, the type of immune response being measured, the adequacy of the experimental procedure, background rearing conditions of the animals, the amount of noise in the animal room, the diet of the animals, or the number of animals housed per cage all remain to be determined. Our purpose has not been to provide a comprehensive review of all of the data relating to the immune system/CNS interaction.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Pavlovian conditioning of shock-induced suppression of lymphocyte reactivity: acquisition, extinction, and preexposure effects.
Recent research has indicated that physical stressors, such as electric shock, can suppress immune function in rats. The present study investigated whether a nonaversive stimulus that had been associated with electric shock would also impair immune function. Presentation of that conditioned stimulus (CS) by itself produced a pronounced suppression of lymphocyte proliferation in response to the nonspecific mitogens, Concanavalin-A (ConA) and Phytohemagglutinin (PHA). In further evidence of a conditioning effect, the suppression was attenuated by extinction and preexposure manipulations that degraded the associative value of the CS. These results indicate that a psychological or learned stressor can suppress immune reactivity independently of the direct effect of physically aversive stimulation or of ancillary changes in dietary and health-related habits.
Animals↗
Shock-induced modulation of lymphocyte responsiveness and natural killer activity: differential mechanisms of induction.
The present study was designed to determine the influence of signaled shock on splenic natural killer (NK) activity and nonspecific T-lymphocyte mitogenic responsiveness. Furthermore, experiments were conducted to examine possible mechanisms mediating this suppression. The results demonstrate that a single session of signaled shock induces suppression of splenic NK activity and T-cell response to the mitogens concanavalin A (Con A) and phytohemagglutinin (PHA). However, the suppression of mitogenic responsiveness was attenuated after five daily sessions of shock, while NK activity remained suppressed. The suppression of NK function was prevented by administration of naltrexone prior to the shock session indicating mediation by opiate receptors. However, naltrexone did not prevent the shock induced suppression of mitogenic responsiveness to Con A or PHA. Diazepam was not effective in preventing the shock-induced suppression of mitogenic responses or NK activity. Collectively, these results demonstrate that mononuclear cell populations in the spleen are differentially affected by the same stressor and that the immune alterations are mediated via different pathways.
Animals↗
2-deoxy-D-glucose modulation of T-lymphocyte reactivity: differential effects on lymphoid compartments.
This study was designed to evaluate the effect of glucoprivation, as induced by 2-deoxy-D-glucose (2-DG) administration, on lymphocyte mitogen reactivity in Sprague-Dawley rats. The results showed that a single injection of 2-DG decreased reactivity in both whole-blood and spleen lymphocytes, as determined by mitogenic stimulation to concanavalin A (Con A) and phytohemagglutinin (PHA). However, the suppressed reactivity for the spleen lymphocytes attenuated with repeated injections, but the whole-blood lymphocytes did not show attenuation. Mitogen assessments of lymphocytes obtained from the thymus indicated that a single injection did not induce suppressed reactivity, but repeated injections induced a pronounced suppression of responsiveness. Furthermore, mitogen assessments of mesentery lymph nodes did not show any effect of 2-DG injections. These results corroborate other findings using electric shock as the stressor, namely that different compartments of the immune system are differentially affected by a stressor.
Animals↗
Stress and enhanced dopamine utilization in the frontal cortex: the myth and the reality.
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3,4-Dihydroxyphenylacetic Acid↗
Changes in pain reactivity induced by unconditioned and conditioned excitatory and inhibitory stimuli.
In three experiments we investigated the effects of aversive-conditioning components on the reactivity of rats to pain. After training in Experiment 1 with a discrete conditioned stimulus (CS) for a shock unconditioned stimulus (US), different groups were exposed to the CS, US, CS/Us compound, just the training context, or none of those immediately prior to a hot-plate test assessing the latency of a paw-lick response. Relative to no exposure and context alone, the CS produced a shorter latency--that is, an apparent sensitization effect--whereas the US produced a longer latency--that is, a hypoalgesic effect--that was actually augmented by the CS/US compound. Furthermore, whereas the US-induced hypoalgesia was unaffected by the opiate antagonist, naloxone, hypoalgesia produced by the CS/US compound was appreciably decremented by the drug. Experiment 2 showed the same effects with parameters more typical of conditioning research. Experiment 3 compared signals for the presence (CS+) and absence (CS-) of the US. The CS- did not itself affect pain reactivity, but in inhibited the effects of the CS+, US, and CS+/US compound. Collectively, the results suggest that a CS+sensitizes the animal to imminent events and also potentiates an opioid reaction that supplants the less effective nonopioid hypoalgesia induced by the US. In contrast, a CS- functions as a general moderator of excitation, inhibiting both sensitization and hypoalgesic effects, whether opioid or nonopioid.
Animals↗
The central nervous system--immune system relationship.
Research investigating the pathogenesis of schizophrenia has demonstrated that cellular immune reactions, such as those that occur in known autoimmune diseases, may participate in producing alterations of the central nervous system. Furthermore, epidemiologic studies of immune-mediated diseases have suggested that activation of the central nervous system by stressful stimuli may be capable of influencing the function of the immune system. In support of that interaction, research using animal models of stress has provided valuable information as to the effect of stress on basic immune function and susceptibility to infectious disease. Possible hormonal and direct mechanisms of the central nervous system-immune system interaction have been proposed.
Autoimmune Diseases↗
Shock-induced modulation of lymphocyte reactivity: suppression, habituation, and recovery.
The present study was designed to evaluate the suppressive effect of different frequencies of signaled-shock presentations on mitogenic reactivity of lymphocytes in Lewis rats, and to assess the recovery of that reactivity at varying times after the shocks. The results showed that the magnitude of decreased reactivity in both the spleen and whole-blood lymphocytes, as determined by mitogenic reactivity to Concanavalin A (Con A), was directly related to the number of shock presentations within a daily session. However, the suppressed reactivity for the spleen cells diminished with repeated sessions of frequent shocks, in contrast to the whole-blood lymphocytes which did not show any habituation. Furthermore, the imposition of different periods of recovery following a single session of frequent shocks showed that the decreased reactivity for the whole-blood lymphocytes extended beyond the immediate period of the shock experience, and took 48 to 96 hours to recover completely. In contrast, the spleen lymphocytes showed complete recovery within 24 hours following the administration of shock. These results establish that the rate of habituation to and recovery from a shock-induced decrease in mitogen reactivity is more rapid for the spleen than whole-blood lymphocytes.
Animals↗
Inhibition as a "slave" process: deactivation of conditioned inhibition through extinction of conditioned excitation.
Rats were used in a conditioned-suppression paradigm to investigate why a conditioned inhibition (CS-) does not extinguish when presented alone. Experiment 1 assessed the role of blocking by excitatory contextual cues and/or an evoked representation of the conditioned excitor (CS+), which had been nonreinforced in compound with the CS-. When the CS+ and context were extinguished prior to presentations of the CS- alone, the CS- showed a retardation effect, evidently reflecting latent inhibition, because no inhibition was detected in controls for which presentations of the CS- alone had been omitted. Experiment 2 showed that the loss of conditioned inhibition (CI) was due to excitatory extinction and not to time since conditioning. Furthermore, when excitation was reconditioned to the extinguished CS+ (Experiment 1), or to a novel CS in the same context (Experiment 2), CI was restored. Two other experiments evaluated whether the maintenance of CI depended upon excitation that was generic in form or associatively tied to the training context. They showed no loss of CI when groups received CS+ extinction in that context, along with concomitant presentations in a different context of the US by itself, for a novel CS, or correlated either positively or negatively with the original CS+. Collectively, the findings argue that CI is a "slave" to excitation, for when excitation is extinguished, CI is deactivated; and yet when excitation is reconditioned to the original or a new CS+ in the same or a different context, CI is restored.
Animals↗