The Role of Foxp3-Expressing Regulatory T Cells and T Helpers in Immunopathogenesis of Multidrug Resistant Pulmonary Tuberculosis

Subpopulation structure of regulatory T cells and T helpers of peripheral blood in patients with newly diagnosed pulmonary tuberculosis depending on the clinical form of disease and sensitivity of Mycobacterium tuberculosis to antituberculosis drugs has been analyzed in this work. It has been shown that the leading part in immune suppression at infiltrative, dissemination, and fibrosis-cavity pulmonary tuberculosis is played by natural regulatory CD4+CD25+Foxp3+-T lymphocytes. Thus we estimate increase of their number in blood by drug-resistance and drug-susceptible patients. It has been demonstrated that in patients with fibrocavernous and infiltrative form of the disease and drug-resistant pulmonary tuberculosis the number of CD4+CD25−Foxp3+-regulatory T cells was increasing. In patients with infiltrative pulmonary tuberculosis, including multidrug-resistant M. tuberculosis, an increased number of CD3+CD4+CD25− T helpers is determined by the pathogenic features of the development of the tuberculosis infection and is connected with the activation of Th1-dependent immune response. Reduction in the number of T-helpers in the blood of patients with dissemination and fibrosis-cavity pulmonary tuberculosis mediates inefficient implementation of cell-mediated protective immunity

Молекулярно-генетические факторы туберкулеза легких

The modulating influence of a causative agent on the character of an immune reaction at lung tuberculosis is analyzed. Peculiarities of immunopathological reactions depending on the etiological version of a disease and the spectrum of bacterial resistance to antituberculous preparations are discussed with the justification of possible approaches to their correction. Main fields of research activity at the Chair of Pathophysiology of the Siberian State Medical University (Tomsk) concerning immunopathology of the tuberculosis infection are presented.В лекции анализируется модулирующее влияние возбудителя на характер иммунного ответа при туберкулезе легких. Обсуждаются особенности иммунопатологических реакций в зависимости от этиологического варианта заболевания и спектра бактериорезистентности к противотуберкулезным препаратам с обоснованием возможных подходов к их коррекции. Представлены основные направления научно-исследовательской работы кафедры патофизиологии Сибирского государственного медицинского университета (г. Томск) в области иммунопатологии туберкулезной инфекции

PECULIARITIES OF CD3/CD28-INDUCED SECRETION OF INTERLEUKIN-2 AND SUBPOPULATION COMPOSITION OF T-LYMPHOCYTES IN PATIENTS WITH PULMONARY TUBERCULOSIS

The article presents the results of the research of CD3/CD28-induced production of interleukin-2 by blood lymphocytes in vitro as well as subpopulation composition of peripheral blood T-lymphocytes in patients with drug-sensitive and drug-resistant pulmonary tuberculosis. We detected the decrease in the total amount of CD3-positive cells and suppression of IL-2- secretion during CD3/CD28-induction of lymphocytes, which was most expressed in a disseminated form of drug-resistant TB. We also demonstrated the reduction in the percentage value of CD3+CD28+IL-2+ and CD3+CD28+IL-2- cells in patients with pulmonary TB against the background of the increase in the percentage value of CD3+CD28-IL-2-. Besides, it was also shown that the detected changes are unidirectional, don't depend on a clinical form of TB and are maximally manifested in patients with a drug resistant variant of the TB process

Экспериментальное обоснование эффективности «массажа» ретинальных вен для лечения окклюзии вен сетчатки

Objective: evaluate the effectiveness of treatment of retinal vein occlusion with the use of “massage” of retinal veins on the experimental model of photoinduced retinal venous occlusive disease.Materials and methods. Studies were carried out on 30 rabbits of the Chinchilla breed (30 eyes) weighing 1.5–2.0 kg. In the first stage of the experiment, for all animals the photoinduced thrombosis were modeled by laser irradiation of its retinal veins for 0.3–0.4 seconds at a density of 200 J/cm2 and a wavelength of 662 nm after the administration of “Photoditazine” at a dose of 2.5 mg/kg weight. In the second stage of the experiment, the animals were divided into the main group and the comparison group, depending on the method of treatment: 15 animals of the main group with “massage” of the retinal vein in the form of 5–7 movements with a silicone tip of the scanner Tano, 15 animals of the comparison group with epiretinal administration of recombinant prourokinase in a dose 500 international units (IU).Results. The formation of a parietal thrombus in the simulation of photoinduced the central retinal vein occlusion in the experiment leads to a slowing of perfusion in the affected vessel by (8.0 ± 2.5) s (according to fluorescence angiography), an increase in the thickness of the central parts of the retina by (70.2 ± 9.7) μm (according to optical coherence tomography), to the appearance of crimp and uneven lumen of the retina veins, extensive plasma and hemorrhages (according to the data of ophthalmoscopy). On the model of retinal veins thrombosis, a new method of treating retinal vein occlusion was tested, which showed significant efficacy. It has been established that the use of “massage” of the affected retinal vein reduces the time of venous perfusion by 1.3 times and 1.45 times accelerates the resorption of the edema of the central parts of the retina compared to enzymatic thrombolysis.Conclusions. “Massage” of the retinal veins is an effective method of treating retinal vein occlusion and is not accompanied by damage to chorioretinal structures during manipulation.Цель работы: на экспериментальной модели фотоиндуцированного тромбоза центральной вены сетчатки и ее ветвей оценить эффективность лечения окклюзии вен сетчатки с применением «массажа» ретинальных вен.Материалы и методы. Исследование проведено на 30 кроликах породы шиншилла (30 глаз) массой 1,5–2,0 кг. На первом этапе эксперимента всем животным моделировали фотоиндуцированный тромбоз при помощи лазерного облучения ретинальных вен в течение 0,3–0,4 с при плотности воздействия 200 Дж/см2 и длине волны 662 нм после введения фотодитазина в дозе 2,5 мг/кг массы. На втором этапе эксперимента животных разделяли на основную группу и группу сравнения в зависимости от метода лечения: 15 животным основной группы выполняли «массаж» пораженной ретинальной вены в виде 5–7 движений силиконовым наконечником скраппера Tano, 15 животным группы сравнения эпиретинально вводили рекомбинантную проурокиназу в дозе 500 международных единиц (МЕ).Результаты. Формирование пристеночного тромба при моделировании фотоиндуцированной окклюзии ретинальных вен в эксперименте приводит к замедлению перфузии в пораженном сосуде на (8,0 ± 2,5) с (по данным флуоресцентной ангиографии), увеличению толщины центральных отделов сетчатки на (70,2 ± 9,7) мкм (по данным оптической когерентной томографии), появлению извитости и неравномерности просвета вен сетчатки, обширных плазмо- и геморрагий (по данным офтальмоскопии). На модели тромбоза ретинальных вен апробирован новый метод лечения окклюзии вен сетчатки, показавший значительную эффективность. Установлено, что применение «массажа» пораженной ретинальной вены сокращает время венозной перфузии и в 1,45 раза ускоряет резорбцию отека центральных отделов сетчатки по сравнению с ферментным тромболизисом.Выводы. «Массаж» ретинальных вен является эффективным методом лечения окклюзии вен сетчатки и не сопровождается повреждением хориоретинальных структур во время манипуляции

Production of angiogenesis mediators and the structure of the vascular wall in the heart in ischemic cardiomyopathy

Background. In the pathogenesis of ischemic cardiomyopathy (ICMP), angiopoiesis remains unexplored.The aim. To describe the vasculature of the heart and the imbalance of angiogenesis mediators in the coronary circulation in association with the number of endothelial progenitor cells (EPC) and desquamated endothelial cells (DEC) in the blood of patients with coronary heart disease (CHD), suffering and not suffering from ICMP.Methods. Fifty-two patients with CHD (30  patients with ICMP, 22  patients without  ICMP), 15  healthy donors were examined. The content of EPC (CD14+CD34+VEGFR2+) in the blood from the cubital vein and DEC (CD45–CD146+) in the blood from the coronary sinus and the cubital vein was determined by flow cytometry. The concentrations of VEGF-A (vascular endothelial growth factor A), PDGF (platelet-derived growth factor), and SDF-1 (stromal cell-derived factor 1) in blood plasma were recorded using immunofluorescence assay; the angiopoietin-2, MMP-9 (matrix metallopeptidase 9) were recorded using enzyme immunoassay. In myocardial biopsies the specific area of vessels and the expression of αSMA (smooth muscle alpha-actin) were determined by morphometric and immunohistochemical methods.Results. In the peripheral blood of patients with CHD, regardless of the presence of ICMP, the DEC content exceeded the physiological level, and the VEGF-A, PDGF, angiopoietin-2, and MMP-9 corresponded to the norm. In CHD patients without cardiomyopathy, there was an excess of SDF-1 and EPC in the blood from the cubital vein, and in ICMP, their physiological significance was noted. In the coronary blood flow in patients with CHD without cardiomyopathy, an increase in the concentration of PDGF was found, which was not determined in patients with ICMP, who had an increased content of DEC, angiopoietin-2 and MMP-9. The specific area of the vessels in the patients of the two groups was comparable; the expression of αSMA in ICMP was 6.2 times lower than in patients with CHD without cardiomyopathy.Conclusion. The development of ICMP is accompanied by impaired maturation of vessels in the myocardium, associated with the absence of a compensatory reaction of activation of cellular and humoral factors of angiogenesis

Клинико-лабораторные особенности инфекционного мононуклеоза у детей в зависимости от этиологии заболевания

Study of clinical and laboratory features of infectious mononucleosis (IM) in children depending on the etiological variant of the disease. The study involved 94 children aged 4 months to 15 years old with a diagnosis of «infectious mononucleosis». The study analyzed the etiologic structure of IM, clinical and laboratory features of its individual etiological variants. The findings showed that the most common cause of myocardial infarction in children under the age of 15 years is HHV-6, which is more common as monoinfection (51.06% of the total number of patients with IM), at least — in association with EBV and CMV. IM mixed etiology recorded in 29.79% of cases. The acute phase of infectious mononucleosis, regardless of the etiology of the disease is accompanied by a moderate leukocytosis, accelerated erythrocyte sedimentation rate, an increase in alkaline phosphatase activity. The level of IL-4 in the blood varies depending on the etiology of the disease and is the highest at the infarction caused by EBV. Severity of the clinical picture varies depending on the etiology of the disease. The most pronounced intoxication, lymphoproliferative and hepatolienalis syndromes were identified in children with IM-EBV, IM-HHV-6 and IM mixed etiology (version «EBV + HHV-6»). Determination of etiologic variant of IM is relevant for the diagnosis of disease, prediction of its course and possible complications.Целью работы было изучение особенностей клинико-лабораторной картины инфекционного мононуклеоза (IМ) у детей в зависимости от этиологического варианта заболевания. Обследовано 94 ребенка в возрасте от 4 месяцев до 15 лет с диагнозом «инфекционный мононуклеоз». В ходе исследования была проанализирована этиологическая структура IМ и клинико-лабораторная картина отдельных его этиологических вариантов. Показано, что наиболее частым возбудителем IМ у детей в возрасте до 15 лет является HHV-6, который чаще встречается в виде моноинфекции (51,06% от общего количества больных IМ), реже — в ассоциации с EBV и CMV. IМ смешанной этиологии регистрируется в 29,79% случаев. Острый период IМ независимо от этиологии заболевания сопровождается умеренным лейкоцитозом, увеличением СОЭ и активности щелочной фосфатазы. Уровень IL-4 в крови варьирует в зависимости от этиологии заболевания и является максимальным при IМ- EBV. Выраженность клинической картины различна в зависимости от этиологии заболевания. Наиболее выраженные интоксикационный, лимфо-пролиферативный и гепатолиенальный синдромы выявляются у детей с IМ-EBV, IМ-HHV-6 и IМ смешанной этиологии (вариант «EBV + HHV-6»). Определение этиологического варианта IМ является актуальным для диагностики заболевания, прогнозирования его течения и возможных осложнений