Аbstract. Present review article considers neuroimmunological issues in pathogenesis of infantile cerebral paralysis  (ICP).  Various  factors  of  immune  system  and  cytokine  regulation  network  (including  TNFα, interleukins) have been shown to participate in development of pathological events in patients with periventricular leukomalacia which result into evolving ICP. Selective cytotoxic activity of TNFα was analyzed as a factor in development of continuous chronic process. A role of immunopathological events for development of cytogenetic rearrangements in peripheral blood cells is proposed. (Med. Immunol., 2011, vol. 13, N 2-3, pp 115-120)

Abstract. Relations of immune tolerance between mother and fetus are considered in view of a common regulatory continuum which is formed under the influence of a growing fetus. To explain such an immune tolerance, a notion of immune system plasticity is introduced, as an analogue to the nervous system plasticity, which develops in response to a continuum of changes occurring in fetal and maternal organisms during the nine months of pregnancy. The immune system plasticity in females is supposed to be among possible factors causing collisions upon conception and in the course of pregnancy. (Med. Immunol., 2011, vol. 13, N 2-3, pp 121-132)

Аbstract. The objective of present study was to determine the immunological features of immune system aging in mucosa-associated lymphoid tissue (MALT) in the patients at different ages (mature, aging and old) observed at a dental unit. A study of cellular spectrum and humoral factors in salivary gland secretions has been performed in a group of 106 persons (35 to 90 years old). A number of age-dependent features of the immune profile were revealed for the mucous-salivary area, thus characterizing involution events within MALT structures. Among specific markers determining intensity of MALT-associated aging, a decreased percentage of viable immune cells (below 40%), along with the prevalence of the neutrophilic granulocytes in the salivary secretions (over 98%) (with increased expression of β2-integrins); decreased counts of mononuclear cells, i.e., mononuclear cells with low expression of CD11β adhesion molecules, B-lymhocytes, and Th-lymphocytes have been revealed. Alterations in serum factors included a general decrease in complement system activity (СН50) and anaphylotoxines (С3а,С5а); elevated protein, mucine, and IgМ levels. The revealed specific features of cellular and humoral immunity within MALT-associated muco-salivary zone may be considered as a normal response connected with natural aging processes. (Med. Immunol., 2011, vol. 13, N 2-3, pp 167-174)

Abstract.  An  immune  deficiency  state,  along  with  continuously  increased  intravascular  coagulation, are  shown  to  develop  in  puerperal  women  after  Caesarian  section  complicated  by  endometritis.  Complex therapeutic schedules aimed for endometritis treatment, including thymic peptides (thymalin or thymogen) are accompanied by more rapid correction of these disorders and favorable clinical effect. (Med. Immunol., 2011,  vol. 13, N 2-3, pp 279-284)

Abstract. We have studied some immune parameters in pregnant women with undifferentiated forms of connective tissue dysplasia (n = 51), who harboured herpesviruses, i.e., cytomegalovirus and Herpes Simplex virus. A relative insufficiency of CD3+ lymphocytes, along with deficiency of CD4+T cells, and predominance of CD16+ cells (NK cells), and CD20+ cells were revealed, accompanied by increase in IgM and the decrease in IgA and IgG levels. Disturbances of cellular and humoral immunity in such patients were more expressed than in women without undifferentiated forms of connective tissue dysplasia (n = 50), being associated with increased  frequency  of  infection  manifesting  as  inflammatory  placental  lesion  with  secondary  placental insufficiency and more pessimistic perinatal outcomes. The results obtained justify a need for second preventive measures  in  pregnant,  herpesvirus-carrying  women with undifferentiated connective tissue dysplasia. (Med. Immunol., 2011, vol. 13, N 2-3, pp 175-180)

Аbstract.  Сlinical  and  immunocorrective  efficiency  of  Roncoleukin®  (IL-2)  monotherapy  applied  as subcutaneous injections versus inhalatory mode of treatment, was studied in patients with chronic recurrent infections. It was shown that administration of Roncoleukin® at a total dose of 1.5 mg was accompanied by increased activity of Th1 lymphocytes and reduced in vitro production of IL-10, and does not exert any adverse immunotropic effects associated with Treg expansion. In general, the positive clinical effect was registered in 65% (26/40) of the patients, and its duration ranged between 3 and 7 months (a mean of 4.4±0.2 months). Clinical  efficiency  of  Roncoleukin®  inhalations  proved  to  be  not  inferior  to  conventional  Roncoleukin® immunotherapy performed by subcutaneous injections (resp., 70 and 60% of positive responses), and allows a more significant prolongation of event-free remission. (Med. Immunol., 2011, vol. 13, N 2-3, pp 227-236)

Abstract. We investigated the ability of autologous/allogeneic mesenchymal stem cells (MSC) from early passages, derived from bone marrow of patients with multiple sclerosis, to inhibit mitogen/myelin-induced proliferation  of  memory  T  cells.  It  was  shown  that  MSC  immunosuppressive  potential  of  myelin-induced T-cell memory proliferation was significantly higher than an appropriate suppressive effect upon mitogenstimulated cells. These data provide an evidence for a possible pathogenetic role of MSCs in suppression of myelin-specific proliferation of effector lymphoid cells. Immunoregulatory mechanisms of mesenchymal stem cells  have  been  determined.  It  has  been  shown  that both soluble factors and cell-mediated interactions may be  involved  in  immunosuppressive  activity  of  MSCs.  Moreover, soluble mediators of MSC immunoregulatory properties, e.c., prostaglandin E2 and indoleamine 2,3-dioxygenase,  were  not  produced  in  constitutive  manner,  but  they  require  a  paracrine  signal  from T-lymphocytes. The data obtained may be used for development of an individual approach, in order to estimate immunomodulatory properties of MSCs and for further application of cell cultures in pathogenetic therapy of multiple sclerosis. (Med. Immunol., 2011, vol. 13, N 2-3, pp 237-246)

Abstract. Shortening of telomeres represents an important mechanism that limits the proliferative potential of cells. Telomeres are chromatin structures that perform capping and protection of the chromosome ends. In vertebrates, they consist of tandem hexameric repeated sequences (TTAGGG) that are associated with various specific proteins. Immune system is extremely susceptible to telomere loss, since cellular proliferation underlies self-renewal of T and B lymphocytes, being also quite necessary for their biological functions. Telomere loss in lymphocytes may contribute to development of immune deficiency, and predispose for autoimmune responses in  the  elderly.  In  this  study,  we  analyzed  telomere  length,  the  rates  of  telomere  loss,  and  the  variability  of telomeres  in  B  cells  from  rheumatoid  arthritis  patients,  and  in  healthy  donors.  Average  values  of  telomere length in healthy donors were found to be, respectively, 1.9 and 2.3 kb longer for B cells, as compared with CD4+ и CD8+Т-lymphocytes. The same tendency was observed in rheumatoid arthritis patients. Estimated rate of telomere loss in B-cells was 20 bp per year in healthy donors, while being slightly faster in rheumatoid arthritis patients. Thus, telomere shortening in B lymphocytes, as well as other senescence mechanisms, may contribute to development of autoimmune disease. (Med. Immunol., 2011, vol. 13, N 2-3, pp 151-156)

Abstract.  The  aim  of  present  study  was  to  evaluate  clinical  and  prognostic  value  of  various  inflammationmarkers  in  patients  after  Q-wave  myocardial  infarction  (MI).  Results:  Among  multiple  inflammation  factors  studied,  only  TNFα,  IL-12  and  CRP  levels  proved  to  be  significantly  increased  in  the  patients  with  multi-vesselcoronary  artery  disease,  as  compared  to  the  patients  with  single  coronary  lesions.  A  positive  correlation  was  revealed  between  the  levels  of  IL-12  and  IL-6  inflammation  markers,  and  severity  of  atherosclerotic  lesions  of  non-coronary  arteries  (brachiocephalic  vessels,  or  lower  limb  arteries).  Regression  analysis,  using  an  iterative  approach,    showed    that    patients’    age    of    ≥    53    years and  IL-12  levels  ≥  87.1  pg/ml  are  of  highest  predictive  value,    when    detecting    clinically    significant    coronary  lesions.    Meanwhile,    the    age    of    ≥    65    years    and    IL-  12  levels    exceeding    108.8    pg/ml    allow    of    detecting  haemodynamically    significant    non-coronary    lesions.  Acute    heart    failure    according    to    Killip    class    II    and  more,  and  IL-12  levels  over  90  pg/ml  have  been  verified  as    independent    variables    for    risk    stratification    of    any    cardiovascular  event  within  a  year  after  MI.  Hence,  among  all  studied  inflammatory  indexes,  IL-12  possesses  the  greatest  diagnostic  value  in  defining  patients  at  a  high  risk  for  severe  coronary  and  multifocal  atherosclerosis  and  subsequent  complications.  (Med.  Immunol.,  2011,  vol.  13,  N  2-3,  pp  219-226)

Abstract. At present time, the main therapeutic goal in bronchial asthma treatment is to achieve complete control of the disease. Appropriate medical evaluation involves  a  complex  system  of  clinical  criteria  and functional  parameters  obtained  by  instrumental  and laboratory  techniques.  Wide  application  of  inhalatory glucocorticosteroids (IGCS) in childhood bronchial asthma treatment, requirements for a long-term therapy, and common IGCS dose-escalation regimens determine an importance of searching novel objective criteria to  predict  efficiency  of  the  therapy  preformed.  In  present  work,  we  propose  a  method  aimed  to  identify glucocorticosteroid-resistant lymphocytes in peripheral blood of the patients with bronchial asthma undergoing IGCS therapy. The results of this study have shown that clinical efficiency of such treatment of bronchial asthma patients, independently on the IGCS dosage, may be evaluated by the degree of steroid-induced suppression of in vitro lymphocyte proliferation caused by a domestic dust antigen. The data obtained may be used in clinical settings to predict efficiency of IGCS therapy and adjust treatment regimens in bronchial asthma patients. (Med. Immunol., 2011, vol. 13, N 2-3, pp 157-166)

Аbstract.  Endometrial  hyperplasia  (EH)  represents  an  excessive  increase  in  thickness  and  volume  of proliferating endometrium accompanied by altered glandular structure. This disorder is higly prevalent among women in their premenopausal period. There exist only scarce data concerning possible role of chemokines and their receptors in EH pathogenesis and clinical course. Hence, the aim of our study was to analyze mRNA expression  of  several  key  chemokines  and  their  receptors  in  endometrial  tissue  samples  from  EH  patients. This work included sixty-three women with disturbed menstrual  cycle  and/or  pathological  changes  of endometrium, as assessed by sonographic studies. The patients were 32 to 61 years old (a mean of 48.4±0.6 years). The levels of mRNA expression were determined by  gene-specific  PCR  in  a  semiquantitative  manner,  whereas promoter genotypes of matrix metalloproteinases (ММР1 -16071G/2G and ММР3 -11715А/6A) were identified by means of allele-specific PCR. Results of the study included a significant increase of mRNA for MIP-1α, eotaxin 2, along with decreased amounts of mRNA for CCR-3 (a specific receptor for eotaxins), in polyps developing from hyperplastic endometrium. MIP-1α synthesis fades away with increasing age. An increased level of MIP-1β was shown in prolonged and recurrent disturbances of menstrual cycle, whereas elevation of MIP-1α and CXCR-1 was registered in cases of multiple pregnancies. In threatening abortions, an increase of MIP-1β gene expression was revealed. Hence, the local chemokine system reacts to inflammatory and hemorrhagic complications with increased mRNA expression of certain chemokine genes. Determination of the chemokine mRNA levels, as well as their receptors in patients with endometrial hyperplasia may reflect a general background of this disorder. (Med. Immunol., 2011, vol. 13, N 2-3, pp 189-196)

Abstract. The article presents data about blood serum cytokine profile in patients with chronic widespread dermatoses, associated with increase in blood markers of endogenous intoxication (EI) syndrome, i.e., lowand medium-molecular mass substances (LMWS). A close interrelation has been revealed between EI levels, and cytokine profiles. In the patients with high amounts of blood LMWS, increased levels of anti-inflammatory IL have been shown. Correlation analysis of clinical and laboratory parameters has demonstrated a leading role of EI in pathogenetic mechanisms of chronic extended dermatoses, and brings about altered regulation of metabolic processes. A severe clinical course of dermatoses (i.e., therapy resistance) was associated with a  considerable  decrease  in  blood  IL-8  and  IL-10  levels,  along  with  high  IgE  and  LMWS  amounts. (Med. Immunol., 2011, vol. 13, N 2-3, pp 205-210)

Abstract. The work deals with quantitative methods developed for estimation of nuclease and proteolytic activities  of  autoantibodies.  By  means  of  these  techniques,  appropriate  catalytic  activities  of  abzyme-type antibodies were studied in patients with diabetes mellitus type 1, and in subjects with autoimmune thyroiditis. Oppositely directed changes of the mentioned catalytic activities have been found for autoantibodies of different specificity.  Autoantibodies  occurring  in  autoimmune  thyroiditis  showed  an  increase  of  both  nuclease  and proteolytic activities. Meanwhile, the autoantibodies in diabetes mellitus had increased nuclease activity, along with decreased proteolytic activity. These findings are suggestive for existence of two pathogenetic mechanisms in organ-specific autoimmune pathology that are associated either with direct involvement of Fab fragments of auto-antibodies in autoimmune destruction, or with complement-dependent lysis mediated by Fc-fragments and  cytotoxic  destruction  of  target  cells  by  cytotoxic T-lymphocytes.  The  unique  site-specific  catalytic autoantibodies  were  established  to  exert  a  selective destructive effect upon target cells, thus making a major contribution to the antibody-dependent mechanisms of cytotoxicity in autoimmune diseases. (Med. Immunol., 2011, vol. 13, N 2-3, pp 145-150)

Abstract.  We  studied  effects  of  Stimforte,  an  immunomodulatory  drug  of  animal  origin,  upon mononuclear leukocytes (MLs) and morphology of lymphoid organs in the course of cyclophosphan-induced immunosuppression. It was demonstrated that Stimforte is able to correct the quantitative and subpopulational composition of splenic MLs, the structure of central and peripheral lymphopoietic tissues, as well as effector cell functions of innate immunity affected by the cytostatic drug. (Med. Immunol., 2011, vol. 13, N 2-3, pp 133-138)

Аbstract.  Patients  with  end-stage  renal  disease  need  their  kidney  functions  to  be  replaced.  Chronic haemodialysis represents a most common method of such substitution treatment. This procedure results in successful survival of such patients for years. Chronic haemodialysis is accompanied by a complication which is known as β2-microglobulin amyloidosis. In this case, amyloid substance consisting of β2-microglobulin (β2-MG) accumulates in bones, ligaments and joints. Biological causes of β2-MG amyloidosis are still not established. To elucidate the role of inflammation in the pathogenesis of β2-MG amyloidosis, the levels of  IL-2,  IL-4,  IL-6,  IL-8,  IL-10,  GM-CSF,  IFNγ, TNFα were quantified in plasma of patients undergoing  long-term haemodialysis. Mean amounts of all the mentioned cytokines in haemodialysis patients proved to be significantly higher than in control group consisting of healthy subjects. When comparing a group receiving standard  dialysis  procedure  versus  a  subgroup  receiving  haemodiafiltration,  a  single  reliable  difference  was revealed for GM-CSF levels (p < 0.04), without any differences shown for other cytokines. With increasing terms of chronic haemodialysis, the levels of IL-2, IL-4, IL-6, IL-8, GM-CSF, IFNγ, TNFα were increased, or, at least, they did not decrease. After three years of dialysis, IL-10 concentrations were statistically indistinguishable from normal levels. In patients undergoing haemodiafiltration, plasma levels of IL-2, IL-4, IL-8, GM-CSF, IFNγ, TNFα did not drop with increasing terms of dialysis. The levels of IL-6 and IL-10 decreased after three years of dialysis, to near-normal levels.In general, these results suggest that IL-10 and IL-6 may be regarded as candidates for further studies as potential markers of β2-microglobulin amyloidosis. (Med. Immunol., 2011, vol. 13, N 2-3, pp 211-218)

Abstract. A group of seventy-six patients with acute viral hepatitis B (HB) was under study, in order to evaluate immunological parameters, and ability of blood mononuclear cells to produce cytokines, as dependent on individual viral loads. The immune parameters were less affected in cases of low viral load. Meanwhile, the immune profiles exhibited maximal alterations in the patients with medium and high viral loads. Most expressed changes of immune parameters are found in patients with moderate and high  virus load. Meanwhile, moderate  HB  viral  loads  are  associated  with  higher  functional  activity  of  B-cells  and  lower  NK  numbers, whereas high viral loads correlated with increased amounts of peripheral B cells and higher CD25+ lymphocyte levels. Increased background cytokine synthesis is revealed in mononuclear cells of the patients with acute HB, being, however, suppressed upon additional functional induction. An increased viral load is associated with decreased basal levels of TNFα synthesis. (Med. Immunol., 2011, vol. 13, N 2-3, pp 181-188)

 

Аbstract. The aim of present study was to investigate an influence of polyclonal activators upon cytokine-producing function of peripheral blood cells in the patients with colorectal adenocarcinomas. It was revealed that the stimulated production of IL-1β, IL-1ra, IL-2, IL-17, IL-18 and IFNγ by whole blood cells treated with polyclonal activators was significantly decreased in colorectal cancer patients, as compared to healthy individuals. The stimulated IL-1ra and IL-17 production was depressed during the tumor progression, along with increased release of TNFα and IL-8. It was found that the stimulation index of polyclonal activators upon production of IL-17 by whole blood cells (i.e., a cytokine production ratio of stimulated versus resting cells) may be used as a reliable pre-surgery predictor of tumor invasion, the latter being an important histopathological parameter for clinical oncologists. (Med. Immunol., 2011, vol. 13, N 2-3, pp 197-204

Abstract. We investigated immunogenic properties of vaccine constructs based on lipid-saponin tubular immunostimulating  complexes  (TI-complexes),  and  an  individual  antigen,  i.e.,  monomeric  and  trimeric forms of porin isolated from Yersinia pseudotuberculosis. An opportunity of enhanced immune response to TI-embedded porin was shown upon addition of echinochrome A (ECA) from sea urchin Scaphechinus mirabilis to TI-complexes. Immunization of mice with such a vaccine preparation results into a more intense specific humoral immune response to monomeric and trimeric forms of porin. (Med. Immunol., 2011, vol. 13, N 2-3, pp 139-144)

Abstract. The  study  considers  some  aspects  of  pathogenetic  mechanisms  underlying  blood  eosinophilic  reactions  developing  in  pulmonary  tuberculosis,  taking  into  account  some  novel  data  obtained  by  means  of  modern  immunological  techniques.  It  was  revealed  that  IL-5  is  among  key  factors  determining  eosinophilic  reactions  of  blood  following  infection  with  M.  tuberculosis.  Blood  serum  IL-5  concentrations  proved  to  be  significantly  higher  in  patients  with  tuberculosis  accompanied  by  eosinophilia.  In  these  cases,  eotaxin  is  a  chemokine,  which  selectively  acts  upon  eosinophilic  cells.  Its  effects  include  prolonged  persistence  of  eosinophils  in  bloodstream,  along  with  initiation  of  eosinophil  adherence  to  vascular  endothelium,  thus  enabling  subsequent  migration  of  eosinophilic  leukocytes  to  the  foci  of  specific  granulomatous  inflammation.  (Med.  Immunol.,  2011,  vol.  13,  N  2-3,  pp  273-278)

Аbstract.  Granulocyte  antigen-specific  autoantibodies  may  be  implicated  into  pathogenesis  of  autoand alloimmune neutropenia, neonatal alloimmune neutropenia, and acute pulmonary insufficiency occurring post-transfusion.  However,  detection  and  identification  of  clinically  significant  granulocyte  antibodies  still represent a technically difficult task. To detect immunoglobulins and/or activated complement on granulocyte surface, we have adapted a Gel Test (ID Micro Typing System, DiaMed, Switzerland) which is commonly applied for diagnostics of RBC-specific antibodies. Our results suggest that the data from this gel test are quite reproducible, and the system may be used for detection of granulocyte-specific antibodies belonging to different immunoglobulin classes. (Med. Immunol., 2011, vol. 13, N 2-3, pp 253-256)

 

Abstract. A new method of enzyme-linked immunosorbent assay (in solid-phase ELISA format) has been developed to determine concentrations of autoantibodies to glutamic acid decarboxylase, as well as an evidencebased methodology is proposed for its medical implications, as a quantitative pathogenetic predictive marker of autoimmune diagnostics in type 1 diabetes mellitus. This technique could be implied for serial production of diagnostic reagent kits, aimed for detection of autoantibodies to glutamic acid decarboxylase by means of ELISA approach. (Med. Immunol., 2011, vol. 13, N 2-3, pp 257-260)

Abstract. General parameters of blood cells and immunity (including minor lymphocyte subpopulations) were determined in 196 healthy children from Chita City and 5 districts of the Chita Region, preceded by preselection of the subjects, using multi-step health evaluation schedules.When analyzing data on red blood cells, erythrocyte color index was found to become stable by the age of 3 years, followed by stabilization of blood hemoglobin content by the age of 7 years. RBC indices become stable at later ages..Basic leukocyte populations reach stability by 11 years, except for the numbers of neutrophilic granulocytes (by 15 years). All the T-cell subpopulations including the minor ones (NKT, HLA-DR+) continue to mature until 18 years, except for T-helpers, that become constant in their numbers after 7 years. Serum IgG levels stabilize by the age of 7 years; IgA and IgM amounts – by 18 years. (Med. Immunol., 2011, vol. 13, N 2-3, pp 261-266)

 

Abstract.  A  study  was  performed  aiming  to  investigate  interactions  between  TNFα  receptor  (TNF1) superfamily and heat shock protein Hsp90, using a Jurkat tumor cell line. The tumor cells cultured in presence of Hsp90 inhibitor (17-AAG) showed increased numbers of cells, presenting surface TNFR1 and FasR, which facilitate  triggering  of  programmed  cell  death.  It  was  also  revealed  that  Hsp90  blockage  under  the  in  vitro conditions causes a decrease in FasL, while not affecting TNFα and sTNFR1 production by the tumor cells. (Med. Immunol., 2011, vol. 13, N 2-3, pp 247-252)

 

Abstract. The study dealt with subpopulation analysis of peripheral blood T-regulatory cells (Treg), and in  vitro  testing  of  immunosuppressive  cytokine  (IL-10,  TGF-β)  production  in  the  patients  with  fibrous/cavernous pulmonary tuberculosis, depending on results of intracutaneous tuberculin tests (Mantoux test). We  have  shown  that  Trn,  natural  T-regulatory  lymphocytes  (CD4+CD25+FoxP3+),  and  TGF-β  cytokine, produced by these cells, play a leading role for immune suppression developing in fibrosis-cavernous pulmonary tuberculosis. Moreover, an imbalance of Treg cell subsets has been revealed in patients with fibrous/ cavernous pulmonary tuberculosis, with either positive, or negative Mantoux reaction, as shown by increased content of Treg cells with CD4+CD25+FoxP3+ phenotype, along with higher amounts of CD4+CD25-FoxP3+ subpopulations, and deficiency of CD4+CD25+FoxP3- Treg lymphocytes in blood samples (in cases of positive Mantoux tests). Increased amounts of CD4+CD25+FoxP3+ Treg cells in peripheral blood of patients with fibrous/cavernous pulmonary  tuberculosis  is  associated  with  increase  in  basal  and  BCG-induced  TGF-β  production,  and decreased in vitro IL-10 secretory potential. (Med. Immunol., 2011, vol. 13, N 2-3, pp 267-272)

 

Abstract. Present study concerned in vitro modifying effects of mevastatin, infliximab, r-met-Hu-sTNF-RI and IL-1ra upon antigen-induced activation of peripheral EBV-specific CD4+T-lymphocytes from the patients with rheumatoid arthritis (RA). When compared with healthy persons, the RA patients have shown significantly decreased  concentrations  of  antigen-activated  EBV-specific  CD4+T-cells.  In  healthy  donors,  mevastatin, infliximab, r-met-Hu-sTNF-RI and IL-1ra did not influence the CD4+, IFNγ+ cell concentrations. Neither there were any effects of the abovementioned drugs upon the numbers of EBV-specific CD4+T-cell subset among cultured  mononuclear  cells  from  RA  patients.  Thus,  the  cells  from  RA  patients  exhibit  a  decreased  in  vitro antigen-induced activation of EBV-specific CD4+T-cells, whereas statins and biological agents do not promote suppression of EBV-specific activation of CD4+T-cells. (Med. Immunol., 2011, vol. 13, n 2-3, pp 285-290)