Tumour-induced suppression of immune response and its correction

Immunosuppressive features of tumour cells are a major obstacle for immunotherapy of cancer. We recently noted that RENCA cells effectively interfere with the in vivo activation of RENCA-specific T cells. To unravel the underlying mechanism, we evaluated the influence of RENCA cells on a mixed-lymphocyte/ tumour reaction as well as an allogeneic mixed-lymphocyte reaction. We observed that RENCA cells were not directly immunosuppressive. Instead, they initiated deviation of an immune response in at least two independent directions: (i) expansion of a population of NK1.1+/CD3+ cells, which was accompanied by elimination of mainly CD4+ lymphocytes, and (ii) production of a leukocyte-derived inhibitory factor. Expression of the costimulatory molecule B7.1 by RENCA cells prevented induction of anergy, while expression of MHC class II molecules prevented expansion of NK1.1+ cells, which was accompanied by a significant decrease in cell death. Hence, an unimpaired response was observed only when RENCA cells expressed B7.1 plus MHC class II molecules. Thus, even if a tumour itself is not immunosuppressive, it can induce a strong deviation of the immune response. It is concluded that the first contact between elements of the immune system and the tumour cell can confer a severe bias on immunoregulatory circuits.     

Analysis of the systemic immune response in HIV-1-infected patients suffering from opportunistic Candida infection

Infection by HIV-1 is a major risk factor predisposing for fungal infection. However, few studies have addressed the immunological status of HIV-1 patients suffering fungal infections. This study examines the status of polymorphonuclear phagocytes (PMN) and T cells in HIV-1-infected patients suffering from mucosal Candida infections. These patients had a more immature population of blood PMN, as detected by lower CD18 expression, than HIV asymptomatics or healthy controls. They also had a selective defect in T cell activation in response to phytohemagglutinin (PHA), but not to stimulation through the T cell receptor by anti-CD3 crosslinking, when compared to HIV-1 asymptomatic patients. This was shown by a decrease in cellular proliferation and cell surface expression of CD69, CD25 and CD71 activation antigens. There was also a severe impairment of IL-2 production upon activation by PHA. IL-10, and TNF secretion was also reduced, whereas IFN-gamma and IL-5 production was not affected. No correlation with viral load, CD4 or CD8 T cell number or clinical stage was found. In conclusion, our results indicate that Candida-infected HIV patients have a selective defect, independent of viral load, CD4 or clinical status, involving some aspects of T cell activation, IL-2 production being severely impaired.     

Pharmacological correction of microcirculation in rats suffering from traumatic brain injury

We investigated the effect of mexicor on functional indices of erythrocytes and the structure of myocardial microcirculation in rats suffering from traumatic brain injury (TBI). At 3, 7, and 12 days after TBI, we measured the concentration of 2,3-diphosphoglycerate (2,3-DPG) and the degree of erythrocyte aggregation and their electrophoretic mobility (EPME) in the blood of rats, as well as analyzing sections of the left ventricular myocardium. The first day after the TBI, we observed a decrease in EPME, an increase of erythrocyte aggregation, and an increase of 2,3-DFG concentration in erythrocytes as compared with intact animals. Intraperitoneal injection of mexicor led to an increase of EPME and 2,3-DPG level and reduced the aggregation of erythrocytes, which was most pronounced during the 3–7 days of the post-traumatic period. Improved functional parameters of erythrocytes were accompanied by the dynamics of regenerative processes in the heart. Intraperitoneal injection of mexicor restrained architectonic damage of microvasculature and cardiomyocytes ultrastructure of the left ventricular myocardium of the heart.     

Variability of anthropometric traits at birth in healthy children and children suffering from acute respiratory diseases in the first year of life

Variation of 5 anthropometric traits at birth in groups of normal children who had suffered from acute respiratory diseases during their first year of life was studied in Russian migrant and native population inhabiting the Western area of Baikal-Amur Railway. It was shown that affected children from migrant and native population had lower average values of all traits, as compared with normal children. In order to reduce the number of variable, the principal component analysis was applied. Stronger similarity was found between groups of normal children from native and migrant populations than between normal children and affected children from one population. This can be the evidence of the formation of similar adaptive norm for children from both Russian populations.     

Change in the catecholamine balance of rat hypothalamus at late periods following local irradiation and its correction with etimizol

A local exposure (15 Gy) of chest caused a disturbance in the metabolism of adrenergic mediators of hypothalamus at later times (1-12 months) after irradiation: this was manifested by a decrease in the noradrenaline level 1 month following irradiation, and by phase changes in the dopamine content and considerable deficiency of deoxyphenylatanine throughout the entire period of observation. The treatment with etymisol normalized the catecholamine balance.     

Humoral immune response in children with iron-deficiency anaemia.

The humoral immune response (as shown by plasma immunoglobulin concentrations and antibody response to diphtheria and tetanus toxoids) was evaluated in 14 children with iron-deficiency anaemia and in 24 normal controls. Mean concentrations of haemoglobin and serum iron and mean transferrin saturation were significantly lower in children with iron-deficiency anaemia than in controls. Serum immunoglobulin concentrations were within the normal range in both groups. Two weeks after immunisation with diphtheria and tetanus toxoids the concentrations of IgG increased significantly in both groups. Antibody titres in iron-deficient children were similar to those of controls before and after immunisation. The mean T-lymphocyte count was significantly lower in iron-deficient children than that in controls, but the mean B-lymphocyte counts were similar in the two groups. These observations suggest that humoral immunity in children is not affected by iron deficiency and that conventional immunisation programmes would be effective in children with iron-deficiency anaemia.     

Change in water temperature on the immune response of Taiwan abalone Haliotis diversicolor supertexta and its susceptibility to Vibrio parahaemolyticus

Taiwan abalones, Haliotis diversicolor supertexta, held in 30 parts/per thousand seawater at 28 degrees C, were injected with TSB-grown Vibrio parahaemolyticus (1.6x10(5) cfu abalone(-1)) and then transferred to 20, 24, 28 and 32 degrees C. All abalones transferred to 32 degrees C died by 72 h. The mortality of V. parahaemolyticus-injected abalone held at 20 and 24 degrees C was significantly lower over 24-96 h, compared to animals held at 28 and 32 degrees C. In a separate experiment designed to measure immune function, abalones held in 30 per thousand seawater at 28 degrees C and then transferred to 20, 24, 28 and 32 degrees C were examined for total haemocyte count, phenoloxidase activity, respiratory burst, and phagocytic activity to V. parahaemolyticus after 24, 72 and 120 h. The phenoloxidase activity and phagocytic activity decreased significantly, whereas respiratory burst increased significantly in abalone transferred to 32 degrees C. It is concluded that transfer of abalone from 28 degrees C to 32 degrees C reduced their innate immunity and resistance against V. parahaemolyticus infection.     

Characteristics of the antitoxic and antibacterial immune response in children with diphtheria

As found in this study, the development of the manifest forms of diphtheria occurred in the presence of lower levels of antitoxic antibodies, than bacterial carrier state. The level of antitoxic antibodies in all patients, irrespective of the time of their examination, was higher than that of antibacterial antibodies. In the dynamics of the disease a considerable increase in antitoxic and antibacterial antibodies was observed in localized and disseminated forms of diphtheria and, to a considerably lesser degree, in toxic and subtoxic forms of diphtheria, while not observed in the process of the formation of bacterial carrier state. The dynamics of a rise in the levels of antitoxic and antibacterial antibodies in the manifest forms of diphtheria infection made it possible to differentiate between the cases of toxigenic Corynebacterium diphtheriae carrier state and those of the disease.     

Energy balance of the myocardium and its correction using antiarrhythmics

Changes in energetic balance (chi) during the transition of myocardium from norm to hypoxia and under antiarrhythmics effect were analysed on a mathematical model of the heart ventricle band. (chi-useful work/consumed energy ratio. Orciprenalin was shown to increase chi in the state close to the norm; quinidine, bretilium, procainamide, propranalol increase chi only under hypoxia; varapamile, as well as lidocain when it improves conduction ought to be effective for each initial (before therapy) state of the myocardium.     

Phenotypic correction of the immune response by L-tyrosine in mice reacting oppositely to sheep erythrocytes

The possibility of transversion of low-reacting mice into high-reacting ones evaluated by the application of the natural immunostimulators. L-tyrosine and thymic polypeptides (taktivin) were compared by their ability for the phenotypical correction of the immune response of the oppositely reacting mice. It was established that under the application of L-tyrosine to oppositely reacting mice the phenotypical correction of the immune response is possible. The dramatic increase in AFC and the AFC-SI secreting IgM is observed in the mice, low-reacting to SRBC in comparison with the high-reacting lines.     

Cryptosporidiosis in young children suffering from diarrhoea in Riyadh, Saudi Arabia.

A one-year study of patients (0-120 months of age) with diarrhoea at King Abdel-Aziz University Hospital (KAUH) in Riyadh, Saudi Arabia, detected two cases of cryptosporidiosis. Stool specimens from 174 children with diarrhoea and negative for other parasitic infection were examined using a safranin-methylene blue stain (S-MB). Two children (L.1%) were showing Cryptosporidium oocysts. None of 50 control children who did not have diarrhoea and was free of Giardia lamblia was Cryptosporidium positive.     

Changes in visual evoked potentials after phosphene electrostimulation in children suffering from myopia

We recorded visual evoked potentials (VEPs) in children suffering from medium and high myopia (3.0 to 6.0 and more than 6.0 D; 28 and 21 patients, respectively); a light flash was used as the stimulus. The VEPs were recorded before and after a curative course of phosphene electrostimulation (PhES; frequency 15 sec⁻¹, 10 to 15 10-min-long everyday sessions). The above course resulted in clear trends toward decreases in the peak latencies of the P60 and P100 VEP components; changes in the latencies of other components were expressed to a lesser extent. In children with medium myopia, the latency of the P60 component decreased, on average, by more than 21% (P < 0.05); in patients with high myopia, the respective decrease was about 12% (P > 0.05). These shifts were accompanied by increases in the mean amplitudes of the P60 and, to a lesser degree, P100 (more expressed in medium myopia). The data obtained allow us to suppose that the PhES course provides increases in the transmission velocity through relay structures of the visual analyzer and in neuronal networks of the visual cortex and also in the number of neuronal units whose activity is reflected in generation of VEPs. Application of the PhES technique is much more effective in relatively moderate myopia. Neirofiziologiya/Neurophysiology, Vol. 40, No. 3, pp. 228–235, May–June, 2008.     

Affinity electrophoresis and its applications to studies of immune response

Affinity electrophoresis (AEP) is a useful technique for separation of biomolecules such as plasma proteins, enzymes, nucleic acids, lectins, receptors, and extracellular matrix proteins by specific interactions with their ligands in electric fields and for the determination of dissociation constants for those interactions. Two-dimensional affinity electrophoresis (2-D AEP), which was newly developed by a combination of isoelectric focusing with AEP, has been used for studies on immune response to haptens. Antihapten antibodies, which were induced by immunization of a mouse with the hapten-conjugated bovine serum albumin, were separated by 2-D AEP into a large number of groups of IgG spots with a few microliters of antiserum. Each group of spots showed an identical affinity for the hapten but different isoelectric points as in the case of monoclonal antibodies specific to the hapten. This enabled us to study the diversification and affinity maturation of antihapten antibodies in the course of immunization of a single mouse. Furthermore, effects of a carrier and a hapten array on the production of antihapten antibodies and the cause of charge heterogeneity of monoclonal antibodies were also examined to understand the molecular basis of the immune response in vivo.     

The effect of the pulsatile electromagnetic field in children suffering from bronchial asthma

From the bibliography it is well known that pulsatile electromagnetic field has an anti-inflammatory and analgesic effect. It causes vasodilatation, myorelaxation, hyper-production of connective tissue and activation of the cell membrane. Therefore our aim was to study the possible therapeutic effect of pulsatile electromagnetic field in asthmatic children. Forty-two children participating in this study were divided in two groups. The 1st group consisting of 21 children (11 females, 10 males, aged 11.8 +/- 0.4 yr) was treated by pulsatile electromagnetic field and pharmacologically. The 2nd group served as control, consisting also of 21 children (11 females, 10 males, aged 11.7 +/- 0.3 yr) and was treated only pharmacologically. Therapeutic effect of the pulsatile electromagnetic field was assessed on the basis of pulmonary tests performed by means of a Spirometer 100 Handi (Germany). The indexes FVC, IVC, ERV, IRV, FEV1, FEV1/FVC%, MEF75,50,25, PEF, PIF and the changes of the flow-volume loop were also registered. The pulsatile electromagnetic field was applied by means of the device MTU 500H, Therapy System (Brno, Czech Republic) for 5 days, two times daily for 30 minutes (magnetic induction: 3 mT, frequency: 4 Hz as recommended by the manufacturer). The results in children of the 1st group showed an improvement of FVC of about 70 ml, IVC of about 110 ml, FEV1 of about 80 ml, MEF75 of about 30 ml, PEF of about 480 ml, PIF of about 550 ml. The increases of ERV, IRV and FEV1/FVC and decreases of MEF25,50 were statistically insignificant. The results in the 2nd group were less clear. The flow-volume loop showed a mild improvement in 14 children. This improvement in the 2nd group was less significant. The clinical status of children and their mood became better. We believe that the pulsatile electro-magnetotherapy in children suffering from asthma is effective. On the basis of our results we can recommend it as a complementary therapy.     

The immune response of white shrimp Litopenaeus vannamei and its susceptibility to Vibrio alginolyticus at different salinity levels

White shrimp Litopenaeus vannamei held in 25 per thousand seawater were injected with TSB-grown Vibrio alginolyticus (1 x 10(4) cfu shrimp(-1)), and then transferred to 5, 15, 25 (control) and 35 per thousand. Over 24-96 h, the mortality of V. alginolyticus-injected shrimp held in 5 per thousand and 15 per thousand was significantly higher than that of shrimp held in 25 per thousand and 35 per thousand, and the mortality of V. alginolyticus-injected shrimp held in 5 per thousand was the highest. Shrimp held in 25 per thousand and then transferred to 5, 15, 25 (control) and 35 per thousand were examined for THC (total haemocyte count), phenoloxidase activity, respiratory burst, superoxide dismutase (SOD) activity, phagocytic activity and clearance efficiency to V. alginolyticus after 12-72 h. The THC, phenoloxidase activity, respiratory burst, SOD activity, phagocytic activity and clearance efficiency decreased significantly for the shrimp held in 5 and 15 per thousand after 12 h. It is concluded that the shrimp transferred from 25 per thousand to low salinity levels (5 and 15 per thousand) had reduced immune ability and decreased resistance against V. alginolyticus infection.