[Bone marrow stromal damage mediated by immune response activity]. / Ostecenje strome kostne srzi u uslovima aktivnosti imunskog odgovora.

The aim of this work was to estimate influence of activated immune response on hematopoiesis in vitro, using the experimental model of BCG immunized BALB/c mice and in patients with chronic immunoactivation: long-lasting infections, autoimmunity or malignancy. We correlated changes in long term bone marrow cultures (Dexter) and NBT reduction with appearance of anemia in patients and experimental model of immunization by BCG. Increased spontaneous NBT reduction pointed out role of macrophage activation in bone marrow stroma damage. Long-term bone marrow cultures showed reduced number of hematopoietic cells, with predomination of fibroblasts and loss of fat cells. This results correlated with anemia and leucocytosis with stimulated myelopoiesis in peripheral blood. Activation of immune response, or acting of any agent that directly changes extracellular matrix and cellularity of bone marrow, may result in microenviroment bone marrow damage that modify hematopoiesis.

[Importance of immunoregulation and erythropoiesis estimation in disorders with activated immune system]. / Znacaj ispitivanja imunoregulacije i eritropoeze u oboljenjima s aktivisanim imunskim sistemom.

Complicated immunoregulatory events in different disorders depend on the pathologic process itself and the phase of disease. Immune parameters aberrations in advanced phase of disease, compared to initial ones, may be significant, making hard the understanding of basic immunoregulatory process of the disease. Intending to explain immune mechanisms in different disorders with activation of the immune system as basic pathogenic event (infections, autoimmune diseases), particularly in advanced phase of the disease, on a parallel with standard laboratory investigations of erythropoiesis (hemoglobin, red blood cell count, hematocrit) the following examinations of the immune system were done: white blood cell count, immunophenotyping of lymphocytes, ability of the phagocytes to reduce NBT, chemiluminescent response after stimulation with opsonized and nonopsonized particles. Analysis of erythropoietic parameters in order to see the consequences of the regulatory mechanisms of the immune system (cytokines, interleukins) on hemopoiesis may enable us to understand the mechanisms of disease with the initial activation of the immune system. Finding anemia might be useful in defining the immunoregulatory mechanisms involved in particular pathologic process important for therapeutic approach.

[Effect of exanguinotransfusion on the immune system of neonate]. / Uticaj eksangvinotransfuzije na imunski sistem novoredjenceta.

Exanguinotransfusion is commonly used during therapeutic procedure in neonates with hyperbillirubinemia risking to cause brain injury of the neonate. This therapy without alternative may couse anemia, hyper or hypotonus, and behavior problems. Those disturbances are not clearly understood yet, but it appears that this process is mediated by the immune system. In order to confirm this hypothesis parallely with clinical examination, we performed the following laboratory investigations: red blood cell count, hemoglobin, hematocrite, white blood cells, natural killer cells, T lymphocyte subsets, ability of the peripheral blood phagocytes to reduce NBT, the phagocytic ability and hemiluminescent response. In the clinical examination the most common finding was hypertonus or hypotonus of the muscules. The values of hemoglobin and hematocrite were reduced, red blood cell count was similar, while the white blood cell particularly the monocyte count was increased compared to the control. The absolute number of T lymphocytes defined by CD2 and CD3 surface marker expression was depleted, while the number of DR positive cells as well as the number of NK cells was increased in group treated with exanguinotransfusion. We have also found an increase of NBT positive cells in the same group. There were no differences in the number of NBT positive cells, when they were prestimulated by PMA. Phagocytic ability was lower compared to the control, while hemiluminescent response was faster remaining on high level for a long time. All those differences remained for several months after exanguinotransfusion.

[Neonatal immune system changes caused by phototherapy]. / Promene u imunskom sistemu novoredjenceta izazvane fototerapijom.

It is noticed that phototerapy may cause disturbance in the behavior and higher incidence of infections in neonate. Moreover an electromagnetic radiation may influence different functions of cells. We examined the effects of pototherapy on the immune system of neonates applied because of hyperbilirubinemia. The examined healthy patients, without signs of infection, anoxia or birth injury. Physical examination, white blood cell count, surface differentiation markers on peripheral blood lymphocytes,and hemiluminescent response of peripheral blood leukocytes were performed before and immediately after phototerapy. Our results showed an increase in the total number of peripheral white blood cells: polymorphonuclears, lymphocytes and monocytes as well as a delay in the chemilumonescence response of the peripheral blood phagocytes with lower values of the pick, suggesting a decrease of their functional ability to respond by respiratory burst. This might be important in the case of bacteriemia when phothoterapy may complicate the existing infection. Those findings are temporary.

[Changes in surface markers on peripheral blood lymphocytes, caused by thymic extract in breast cancer patients]. / Promene povrsinskih markera limfocita periferne krvi izazvane primenom ekstrakta timusa kod bolesnica s karcinomom dojke.

A quantification of peripheral blood CD2, CD3, CD4, CD8 i CDDR positive cells was performed to evaluate effectiveness of a bovine thymic extract, TFX-thymomodulin in expresing those surface markers, modulated by postoperative radiotherapy in breast cancer patients. Twenty patients with histologically proven breast cancer, assigned to clinical stage II using the criteria of TNM (Tumour Node Metastasis) classification were divided into two compatative groups: the first one was treated with radiotherapy only, whereas the second one was additionally treated with TFX-thymomodulin. The quantification of CD2, CD3, CD4, CD8 and CDDR positive peripheral blood cells was performed before and after treatment in both comparative groups, using the indirect immunofluorescent technique. We found significantly lower reduction in CD4 and CDDR positive cells in the breast cancer patient group, treated with radioimmunotherapy, compared to the group, treated with radiotherapy only. TFX-thumomodulin could be effective in reducing the changes of examined surface markers, caused by radiotherapy in breast cancer patients.

[Immunophenotyping in diagnostic and classification of leukemia]. / Imunofenotipizacija u dijagnostici i klasifikaciji leukemija.

Markers of differentiation on cell membrane are recognized by monoclonal antibodies, capable to define more precisely the level of cell maturation. The immunofluorescent method, used in this work, is based on the discoveration of surface molecules by means of fluorescein labeled monoclonal antibodies. 74 patients with leukemia, 11 children and 63 adults persons, have been examined. The results show that malignant cells express certain markers characteristic for some forms of leukemias. The most common marker expression in pre-B ALL was: CD34, CD10, CD22, CD24, CD19 and DR. Expression of CD10 marker was characteristic for CALLA + pre-B ALL cells. T leukemias expressed CD38, CD2, CD3, CD4 and CD8 markers. The expression of CD36, CD13, CD14, CD15, CD11b and DR markers was seen in AML. Surface markers may determine type of leikemia. Immunophenotyping of leukemias has enabled us to make a precise diagnostic, determine its prognosis, and select appropriate therapeutic approach.