Augmented platelet calcium uptake in response to serotonin stimulation in patients with major depression measured using Mn2+ influx and 45Ca2+ uptake

There is an augmented platelet intracellular calcium response to serotonin stimulation in major depression. The role that calcium influx has in this process is not known. The objective of this study was to determine platelet calcium influx in response to serotonin by two methods, Mn2+ influx and 45Ca2+ uptake, in order to observe if the uptake response to serotonin was augmented in major depression by comparing the response to normal controls. The use of the two methods of calcium influx showed that serotonin stimulates calcium uptake into platelets. Furthermore, patients with major depression have significantly augmented platelet calcium uptake in response to serotonin. The interesting finding was that calcium uptake into platelets is biphasic, occurring immediately and after five minutes. These results may support the two pool model for calcium oscillations within cells whereby extracellular calcium is needed for intracellular calcium release, and for replenishment of depleted stores once intracellular calcium is released.     

Trypanosoma cruzi: homocytotrophic antibody response in mice immunized with unrelated antigens.

The homocytotropic antibody response to unrelated antigens of mice with acute or chronic infection with Trypanosoma cruzi was studied. The production of IgG1 and IgE antibodies was observed in animals immunized with ovalbumin. The levels of IgG1 and IgE antibody were determined by passive cutaneous anaphylaxis. There was a depression in both IgG1 and IgE when infection and immunization were simultaneous. This depression was more intense when the animals were immunized 3 days after infection. A depression of IgG1 but not of IgE was observed in the animals with chronic infection and in the animals infected during the course of the humoral antibody response (12 days after immunization). It is suggested that a loss of T-cell regulatory mechanism may explain these results.     

Modes and rates of selfing and associated inbreeding depression in the self-incompatible plant Senecio squalidus (Asteraceae): a successful colonizing species in the British Isles

The strength of the self-incompatibility (SI) response in Senecio squalidus was measured across its British range. Geographic variation in SI was investigated and the extent and inheritance of pseudo-self-compatibility (PSC) and inbreeding depression were determined. Mean self-fruit-set per capitulum was calculated for individuals and sample populations. The heritability of PSC and the magnitude of inbreeding depression were assessed by comparing selfing rates and fitness trait values between SI and PSC parent-progeny lines. SI was found to be strongly expressed in S. squalidus throughout its British range, with only 3.1% of the individuals sampled showing PSC. This PSC had relatively low heritability with stronger expression of SI in selfed progeny relative to PSC parents. Inbreeding depression was shown to be great in S. squalidus, with mean life history stage values ranging from 0.18 to 0.25. The strength of SI in S. squalidus appears not to have weakened in response to its rapid colonization of Britain. The avoidance of inbreeding depression is likely to be the primary factor maintaining strong SI in this successful colonizing species.     

The specificity of platelet glutamate receptor supersensitivity in psychotic disorders

Hypoglutamatergic function is implicated in the pathogenesis of schizophrenia, and supersensitivity of platelet NMDA receptors has been reported in schizophrenia. The aim of this study was to examine the platelet glutamate receptor sensitivity in patients with schizophrenia (n=12), mania with psychotic features (n=10) and depression with psychotic features (n=10) and matched controls (n=12) in order to assess if this is a marker of schizophrenia or occurs in other psychotic conditions. Glutamate receptor sensitivity was assessed using the intracellular calcium response to glutamate measured with spectrofluorometry. The percentage response of the schizophrenic and depressed psychotic subjects to glutamate stimulation was significantly greater than control subjects (p<0.005). The mania with psychotic features group was not significantly different to controls. This data suggests that platelet glutamate receptors may be supersensitive in schizophrenia and depression with psychotic features. Furthermore, the platelet may be a possible peripheral marker of glutamate function in schizophrenia and depression with psychotic features.     

Studies on the control of antibody synthesis. XVI. Effect of immunodepression on antibody affinity

The relationship between depression in the magnitude of the immune response and a decrease in affinity of the antibody produced was examined in three different models of immuno-depression (B-cell clonal deletion tolerance, specific suppressor T-cell activity, and anti-genie competition). In B-cell clonal deletion tolerance and in antigen-specific, suppressor T-cell-mediated immunodepression, a small decrease in magnitude (50% or less) is associated with a marked decrease in high-affinity, plaque-forming cells. In contrast, with nonspecific immunodepression, due to antigenic competition, a depression in affinity is only seen when there is a marked (85%) reduction in the magnitude of the response. The results are consistent with the view that when the mechanism of immunodepression involves interaction of antigen with antigen-specific B cells there is a disproportionate loss of high-affinity, antibody-producing cells relative to the decrease in magnitude. In contrast, with nonspecific immuno-depression, where the decrease in affinity is presumably due to inefficient expansion of high-affinity clones, an effect on affinity is only observed in association with a marked depression in the magnitude of the response.     

Diphasic ventilatory response to hypoxia in newborn lambs

The ventilatory response of newborn lambs to hypoxemia was evaluated in two groups of seven awake lambs studied at 2 and 7 days of life. Minute ventilation (VE) and airway occlusion pressure (P0.1) were monitored as the animals were exposed in sequence to room air, 12% O2 (15 min), 7% O2 (15 min), and room air. On 12 and 7% O2, 2-day-old lambs experienced a brisk hyperventilation followed by a VE depression, previously described in newborns of other species (diphasic response). The 7-day-old lambs had a clear diphasic VE response only on 7% O2 breathing. In the 2-day-old lambs, at the time of the relative VE depression to 12% O2, the respiratory centers showed a persisting responsiveness to further hypoxia; switching to 7% O2 caused a brisk increase in VE and P0.1 of 70 and 130%, respectively, which was followed again by a VE depression. The magnitude of the immediate VE response to hypoxia, taken as an index of the chemoreceptor strength, was inversely related to the magnitude of the VE depression (R = 0.81, P less than 0.001). It was concluded that 1) lambs as well as other neonates have an age-related diphasic VE response to hypoxia; 2) at the time of the VE depression, the respiratory centers maintain their responsiveness to further acute hypoxia; and 3) the weakness of the chemoreceptors in the newborn is a major determinant of the diphasic response.     

Nonlinear summation of contractions in cat muscles. I. Early depression

Nerves to fast- and slow-twitch cat muscles were stimulated with various numbers of supramaximal pulses under isometric conditions. By subtracting the force produced by j - 1 pulses from that produced by j pulses, the contribution of the j th pulse could be compared with the response to one pulse (twitch response). A less-than-linear summation (depression) was observed during the rising phase of the twitch. This depression became increasingly prominent and longer in duration with repetitive stimulation. A more-than-linear summation (facilitation) was observed during the falling phase of the twitch, which became increasingly delayed and smaller in amplitude with repetitive stimulation. The early depression could be abolished for the first few pulses by Dantrolene [1-(5-p-nitrophenyl) furfurilidene amino hydantoin sodium hydrate], which reduced Ca++ release from the sarcoplasmic reticulum. The depression was less prominent at short muscle lengths or with stimulation of single motor units. A first-order, saturable reaction such as Ca++ binding to troponin or actin binding to myosin can quantitatively account for the early depression.     

Maternal oxytocin response during mother-infant interaction: associations with adult temperament

Oxytocin is a neuropeptide associated with social affiliation and maternal caregiving. However, its effects appear to be moderated by various contextual factors and stable individual characteristics. The purpose of this study was to investigate the relationship of self-reported state and trait measures (such as temperament, mood and affect) with peripheral oxytocin response in mothers. Fifty-five first-time mothers participated in a semi-structured procedure, during which time repeated peripheral oxytocin levels were measured before, during and after an episode of mother-infant interaction. The maternal oxytocin response was then calculated, based on the difference in oxytocin concentration between initial baseline and interaction phase. Mothers also completed state measures of positive and negative affect and depression, and trait measures of temperament, personality disturbance and depression across time. Regression analyses determined which factors were independently associated with maternal oxytocin response. The trait measure of adult temperament emerged as a significant predictor of oxytocin response. Two out of four Adult Temperament Questionnaire factor scales were independently associated with oxytocin response: Effortful Control was negatively associated, whereas Orienting Sensitivity was positively associated. No state measure significantly predicted oxytocin response. The results indicate that mothers who show an increased oxytocin response when interacting with their infants are more sensitive of moods, emotions and physical sensations; and less compulsive, schedule driven and task oriented. These findings link differences in individual temperament in new mothers with the peripheral oxytocin response, which may have implications in the pharmacologic treatment of disorders such as maternal neglect, post-partum depression and maternal addiction. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.     

Increased serum IgM antibodies directed against phosphatidyl inositol (Pi) in chronic fatigue syndrome (CFS) and major depression: evidence that an IgM-mediated immune response against Pi is one factor underpinning the comorbidity between both CFS and depression

Major depression and chronic fatigue syndrome (CFS) are accompanied by signs of oxidative and nitrosative stress (O&NS) and an inflammatory response. Phosphatidyl inositol (Pi) is thought to play a role in depression. The aim of the present study is to examine whether depression and CFS are characterized by an IgM-mediated immune response directed against Pi. Toward this end, this study examines the serum IgM antibodies directed against Pi in 14 patients with major depression, 14 patients with CFS, 14 subjects with partial CFS, and in 11 normal controls. We found that the prevalence and mean value for the serum IgM levels directed against Pi were significantly greater in patients with major depression and CFS than in normal controls and patients with partial CFS. There were significant and positive correlations between serum IgM levels directed against Pi and two symptoms of the FibroFatigue Scale, i.e. fatigue and depression. The results show that an IgM-related immune response directed against Pi may occur in both depression and CFS and may play a role in the pathophysiology of the key symptom of CFS and major depression. It is suggested that the above disorders in Pi result from increased O&NS in both depression and CFS. Autoanti-Pi antibodies may have biological effects, for example, by changing inositol 1,4,5-triphosphate (IP3), phosphatidylinositol-4,5-bisphosphate (PIP2), diacylglycerol and phosphatidylinositol-3,4,5-triphosphate (PIP3) production, thus interfering with intracellular signalling processes. Future research in major depression and CFS should focus on the functional consequences of the immune responses directed against Pi.     

Antidepressant effects of combination of sleep deprivation and early evening treatment with melatonin or placebo for winter depression

Patients with winter depression (seasonal affective disorder) respond beneficially to sleep deprivation and bright light, but the mechanisms of these responses remain unknown. The study was designed to test whether afternoon/evening melatonin can prevent further relapse after sleep deprivation (presumably due to a pharmacologically induced advance shift of circadian phase). Compared to phase advancing by alteration of sleep - wake schedule or by bright light exposure, the melatonin intake is a more tolerated treatment procedure, and it provides a possibility of blind comparison between chronotherapeutic and placebo treatments. The depression was scored in 16 female patients with winter depression and 17 age-matched female controls before and after total night sleep deprivation and after subsequent six-day administration of melatonin (0.5 mg) or placebo under double blind conditions. The melatonin intake was scheduled at 17:00 in order to produce a phase advance of circadian rhythms. Sleep deprivation resulted in 38% reduction of depression score in patients, but it did not reduce depression score in controls. After subsequent treatment with placebo or melatonin, slight but significant improvement of mood was found in controls. These treatments also stabilized the antidepressant response to sleep deprivation in patients. However, neither differential effect of melatonin and placebo on depression score nor alteration of habitual sleep timing was found in patients and controls. Thus, the study results do not provide evidence for the antidepressant potential of melatonin in patients with winter depression under realistic clinical conditions. The finding of stabilization of mood in patients with placebo points to the contribution of psychological factors to the therapeutic action of this and other types of innovative treatments for winter depression. To include psychosocial aspects in the theoretical framework of seasonal depression, we conceptualized depression as an evolved feature of emotional response to psychosocial rather than physical environment. The seasonality of depression might be explained by cumulative effects of aperiodical psychosocial factors and periodical physical factors on one of the mechanisms of brain neurotransmission.     

Nitric oxide-dependent and -independent mechanisms are involved in TNF-alpha -induced depression of cardiac myocyte contractility

Previous studies have demonstrated the presence of myocardial depression in clinical and experimental septic shock. This response is mediated, in part, through circulating TNF-alpha-induced, nitric oxide-dependent, depression of basal myocyte contractility. Other mechanisms of early myocardial dysfunction involving decreased response to adrenergic stimulation may exist. This study evaluated the presence and nitric oxide dependence of impaired adrenergic response to TNF-alpha in in vitro cardiac myocytes. The contraction of electrically paced neonatal rat cardiac myocytes in tissue culture was quantified using a closed-loop video tracking system. TNF-alpha induced depression of baseline contractility over the first 20 min of cardiac myocyte exposure. This effect was blocked by N-methyl-arginine (NMA), a nitric oxide synthase inhibitor, in all studies. Contractile and cAMP response to increasing concentrations of isoproterenol was deficient in cardiac myocytes exposed to TNF-alpha regardless of the presence of NMA. In contrast, increasing concentrations of forskolin (a direct stimulant of adenylate cyclase) and dibutyryl cAMP (a metabolically active membrane-soluble analog of cAMP) completely reversed TNF-alpha-mediated depression, though only in the presence of NMA. Forskolin-stimulated cAMP generation remained intact regardless of NMA. Increasing concentrations of exogenous calcium chloride, unlike other inotropic agents, corrected TNF-alpha-mediated defects of contractility independent of the presence of NMA. These data suggest that TNF-alpha exposure is associated with a second nitric oxide-independent but calcium-dependent early depressant mechanism that is manifested by reduced contractile and cAMP response to beta-adrenergic stimulation.     

Predictors of response to combined wake and light therapy in treatment-resistant inpatients with depression

ABSTRACT

There is growing evidence for combined chronotherapeutic interventions as adjunctive treatments for major depression. However, as the treatments can be demanding, we need to identify predictors of response. This study aimed to describe predictors of response, remission and deterioration in the short-term phase, as well as predictors of long-term response. The predictors investigated were gender, type of depression, severity of depression, treatment resistance, quetiapine use, general self-efficacy, educational level and positive diurnal variation. Follow-up data from 27 inpatients with moderate-to-severe depression participating in a chronotherapeutic intervention were analysed. As a supplement to standard treatment, they completed 3 wake therapy sessions in the first week, 30 min daily light treatment and sleep-time stabilisation in the entire 9-week study period. Patients had a significant decrease of depressive symptoms during the first 6 days measured by HAM-D6. At Day 6, 41% of the patients responded to the treatment and 19% fulfilled the criteria of remission. Deterioration by the end of wake therapy sessions was however not uncommon. In the short-term phase, mild degree of treatment resistance was associated with remission and low educational level associated with deterioration. Positive diurnal variation (mood best in the evening) was a predictor of both short-term and long-term response to combined wake and light therapy. Furthermore, patients with evening chronotypes (measured with morningness-eveningness score) were more responsive. Our results suggest that targeting the combined chronotherapeutic intervention at patients with positive diurnal variation and evening types is a viable option.     

Fresh-water fish chemoreceptors responsive to dilute solutions of electrolytes

The existence of the palatal chemoreceptors responding specifically to dilute solutions of salts with monovalent cations was demonstrated in carp. The distilled water effect (a response produced by the application of distilled water after chemoreceptors had been rinsed out with hypertonic salt solutions) was assigned to the activity of the same receptor. Intensity of the response to dilute solutions of salts depended on the valency of the anion: the larger the valency, the greater the response. Positively charged sites of the receptor responsive to dilute salt solutions were suggested by previous treatments with acid and alkali, and dye salts. Increase in the ionic strength of the stimulating solution by the addition of supporting electrolytes caused a depression of response. In particular, strong depression of response was caused by the addition of a supporting electrolyte with a divalent cation. Effects of polarizing current on the chemoreceptor activity were investigated. Based upon the findings in this paper, a hypothesis is presented, which explains mechanisms underlying chemoreceptor responses to dilute solutions of electrolytes in terms of an interfacial electro-kinetic process.     

Psychological distress, depression and prolactin response in stressed persons

We examined the relationship of psychological distress to serum prolactin response in 54 persons who had lost a spouse or were threatened with a loss. We found that our two measures of psychological distress, both separation anxiety and depression, were directly correlated with prolactin response during a stressful interview (p less than .05). When we stratified the sample first by depression score and then by separation anxiety, we found a positive correlation between separation anxiety and prolactin response only in the highly depressed half of the sample (r = .32) and a positive correlation between depression and prolactin response only in the highest quartile of intensity for separation anxiety (r = .49, p less than .05). This suggested that both depression and separation anxiety, each in conjunction with high levels of the other but not independently, rendered the individual under stress more physiologically sensitive to distressing challenges such as a stressful interview. Alternatively, it was global distress above a certain threshold that was associated with degree of physiological response.     

CO2 sensitivity of cat phrenic neurogram during hypoxic respiratory depression

The CO2 response of the phrenic neurogram before and during CO-induced isocapnic brain hypoxia was studied in peripherally chemodenervated, vagotomized, paralyzed, ventilated cats with blood pressure held constant. During inhalation of 0.5% CO in 40% O2, arterial O2 content (CaO2) was reduced to 40% and minute phrenic activity to 38.4 +/- 9.4% (SE; n = 9) of prehypoxic levels, primarily due to depression of peak phrenic amplitude (PP). CO2 response, defined as the slope of the plot of PP vs. end-tidal PCO2 during CO2 rebreathing, was unaffected by phrenic depression even to the point of total suppression of phrenic activity in two cats. The effect of the tissue metabolic acidosis associated with hypoxia on phrenic CO2 sensitivity was assessed in a separate group of cats by blocking lactate formation during hypoxia with dichloroacetate (DCA). Preventing lactic acidosis during hypoxia did not affect the CO2 response of the phrenic activity during hypoxia. We conclude that 1) hypoxic depression does not limit the ability of central respiratory neurons to respond to CO2, and 2) the failure of DCA to affect the CO2 response of the phrenic neurogram suggests that brain intracellular lactic acidosis does not modify the phrenic response to hypercapnia.     

Functional disability of rat splenocytes provoked to lipid peroxidation by cumene hydroperoxide

Rat splenocytes were provoked to lipid peroxidation in a dose-dependent manner by cumene hydroperoxide. After exposure to cumene hydroperoxide, formation of high molecular weight protein, presumably through cross-linking of lower molecular weight protein, was stimulated in splenocytes as well as in erythrocyte ghosts. The mitogenic response to concanavalin A of splenocytes was remarkably depressed by addition of cumene hydroperoxide to cultures. This depression was due rather to failures of splenocytes in responding to concanavalin A than deactivation of concanavalin A molecules. It is notworthy that the viability of splenocytes was unaffected by cumene hydroperoxide under the culture conditions where the mitogenic response was depressed. The addition of alpha-tocopherol or thiourea could block the depression of mitogenic response by cumene hydroperoxide, indicating that the depressed response to concanavalin A was related to radical formation. Overall evidence suggests that the function of immunocompetent cells can be depressed through lipid peroxidation-associated mechanisms without suffering from lethal damage.     

Signaling for myocardial depression in hemorrhagic shock: roles of Toll-like receptor 4 and p55 TNF-alpha receptor

Hemorrhagic shock causes myocardial contractile depression. Although this myocardial disorder is associated with increased expression of tumor necrosis factor-alpha (TNF-alpha), the role of TNF-alpha as a myocardial depressant factor in hemorrhagic shock remains to be determined. Moreover, it is unclear which TNF-alpha receptor mediates the myocardial depressive effects of TNF-alpha. Toll-like receptor 4 (TLR4) regulates cellular expression of proinflammatory mediators following lipopolysaccharide stimulation and may be involved in the tissue inflammatory response to injury. The contribution of TLR4 signaling to tissue TNF-alpha response to hemorrhagic shock and TLR4's role in myocardial depression during hemorrhagic shock are presently unknown. We examined the relationship of TNF-alpha production to myocardial depression in a mouse model of nonresuscitated hemorrhagic shock, assessed the influence of TLR4 mutation, resulting in defective signaling, on TNF-alpha production and myocardial depression, and determined the roles of TNF-alpha and TNF-alpha receptors in myocardial depression using a gene knockout (KO) approach. Hemorrhagic shock resulted in increased plasma and myocardial TNF-alpha (4.9- and 4.5-fold, respectively) at 30 min and induced myocardial contractile depression at 4 h. TLR4 mutation abolished the TNF-alpha response and attenuated myocardial depression (left ventricular developed pressure of 43.0 +/- 6.2 mmHg in TLR4 mutant vs. 30.0 +/- 3.6 mmHg in wild type, P < 0.05). TNF-alpha KO also attenuated myocardial depression in hemorrhagic shock, and the p55 receptor KO, but not the p75 receptor KO, mimicked the effect of TNF-alpha KO. The results suggest that TLR4 plays a novel role in signaling to the TNF-alpha response during hemorrhagic shock and that TNF-alpha through the p55 receptor activates a pathway leading to myocardial depression. Thus TLR4 and the p55 TNF-alpha receptor represent therapeutic targets for preservation of cardiac mechanical function during hemorrhagic shock.     

Antidepressant effects of mono- and combined non-drug treatments for seasonal and non-seasonal depression

The involvement of chronobiological mechanisms in the antidepressant response to such non-drug treatments as bright light, physical exercise and sleep deprivation still remain to be clarified. We compare the efficacy of several treatment strategies for seasonal and non-seasonal depression and discuss possible the contribution of chronobiological and psychological mechanisms in antidepressant response. The therapeutic effects were tested at the medical academic hospital near Novosibirsk (55 degrees North) in 138 subjects, either with winter depression or with non-seasonal depression or without depression (n = 41, 64 and 33, respectively). One-week monotreatments were either 2-hour 2500 lux cool-white incandescent light from 14:00 (n = 9, 9, 9, respectively) or 1-hour physical exercise from 13:00 (n = 9, 9, 9, respectively). One-week combined treatments included a night of total sleep deprivation followed by either 2-hour bright light from 14:00 (n = 8, 12, 0, respectively) or 1-hour physical exercise either under ordinary room light from 13:00 (n = 0, 12, 0, respectively) or under bright light from 12:00 (n = 5, 11, 0, respectively). The results indicate that, in subjects left without antidepressant treatment for a week (n = 10, 11, and 15, respectively), the 21-item Hamilton Depression Rating Scale score did not change significantly. The beneficial effects of total sleep deprivation were similar in seasonal and non-seasonal depression. The seasonals exhibited better response to bright light compared to non-seasonals. After sleep deprivation the substantial further improvements were produced by either lighting or exercising. Compared to the patients exercising under ordinary room light, the patients exercising under bright light did not gain an additional benefit. In general, winter depression was well-treated with either exercise or light, while the most promising treatment for non-seasonal depression was physical exercise combined with sleep deprivation. Bright light or physical exercise administered in the middle of the day were not less favorable compared to the treatments in the morning hours, although it is unlikely that they considerably challenged patient's chronobiology. It was concluded that the placebo effect would account for a large portion of clinical response to open non-pharmacological treatments. Therapeutic hops and visibility of such treatments would explain their high antidepressant efficacy in comparison with pharmacological trials applying a double blind cross-over design. In particular, the excellent response of patients with winter depression to light therapy might be related to their tendency to attribute a high symbolic value to bright light and associate their bad mood with a dark season.     

The antioxidant,U74389, ameliorates the depression of vascular reactivity caused by lipopolysaccharide

There is growing evidence that an oxidant stress contributes to the deleterious effects of bacterial lipopolysaccharide (LPS). The present study evaluated the ability of the antioxidant, U74389, to prevent the depression of vascular reactivity caused by LPS. Aortic rings taken from rats given LPS showed a depression of maximum force in response to phenylephrine that was reversed by an inhibitor of nitric oxide synthase. Pretreatment of animals with U74389 attenuated this depression of vascular reactivity. U74389 did not limit the increase in serum tumor necrosis factor levels caused by LPS. These results show that U74389 can ameliorate the depression of vascular reactivity caused by LPS possibly by interfering with the induction of nitric oxide synthase.     

Differential immunosuppressive effects of ascites fluid from mastocytoma-bearing mice on primary vs secondary immunocyte responses.

The effects of immunosuppressive ascites fluids from mastocytoma-bearing mice on the primary vs secondary immune response to sheep red blood cells (SRBC) was examined. Injection of mice with ascites fluid from tumor-bearing mice markedly depressed the primary immune response of normal syngeneic mice challenged with SRBC. However, there was a preferential depression of the 19S IgM antibody response as compared with the 7S IgG response. Injection of ascites fluid shortly before secondary immunization of mice with SRBC also resulted in depressed IgM PFC responses but only a slight to moderate depression of IgG PFC. Treatment of mice with the ascites fluid before primary immunization had little if any effect on the secondary IgG PFC response, although the IgM response was moderately depressed. These results indicate that the immunosuppressive factor(s) present in the ascites fluid of mastocytoma-bearing mice has a differential effect on distinct classes of immunocytes. Those immunocytes or their precursors involved in formation of low efficiency 7S IgG antibody are more resistant to immunodepression. Such differences appear due to different sensitivities of cells involved in the immune response system.