Immunopathological Changes Research Articles

Pig-to-human kidney xenotransplants using genetically modified minipigs

This study develops an observational model to assess kidney function recovery and xenogeneic immune responses in kidney xenotransplants, focusing on gene editing and immunosuppression. Two brain-dead patients undergo single kidney xenotransplantation, with kidneys donated by minipigs genetically modified to include triple-gene knockouts (GGTA1, β4GalNT2, CMAH) and human gene transfers (hCD55 or hCD55/hTBM). Renal xenograft functions are fully restored; however, immunosuppression without CD40-CD154 pathway blockade is ineffective in preventing acute rejection by day 12. This rejection manifests as both Tcell-mediated rejection and antibody-mediated rejection (AMR), confirmed by natural killer (NK) cell and macrophage infiltration in sequential xenograft biopsies. Despite donor pigs being pathogen free before transplantation, xenografts and recipient organs test positive for porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV) by the end of the observation period, indicating reactivation and contributing to significant immunopathological changes. This study underscores the critical need for extended clinical observation and comprehensive evaluation using deceased human models to advance xenograft success.

SARS-CoV-2 infection induces thymic atrophy mediated by IFN-γ in hACE2 transgenic mice.

Pathogenic infections cause thymic atrophy, perturb thymic T-cell development, and alter immunological response. Previous studies reported dysregulated T-cell function and lymphopenia in coronavirus disease-19 (COVID-19). However, immunopathological changes in the thymus associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection have not been elucidated. Here, we report that SARS-CoV-2 infects thymocytes, and induces CD4+CD8+ (double positive; DP) T-cell apoptosis leading to thymic atrophy and loss of peripheral TCR repertoire in K18-hACE2 transgenic mice. Infected thymus led to increased CD44+CD25- T-cells, indicating an early arrest in the T-cell maturation pathway. Thymic atrophy was notably higher in male hACE2-Tg mice than in females and involved an upregulated de-novo synthesis pathway of thymic glucocorticoid. Further, IFN-γ was crucial for thymic atrophy, as anti-IFN-γ -antibody neutralization bluntedthymic involution. Therapeutic use of Remdesivir also rescued thymic atrophy. While the Omicron variant and its sub-lineage BA.5 variant caused marginal thymic atrophy, the delta variant of SARS-CoV-2 exhibited severe thymic atrophy characterized by severely depleted DP T-cells. Recently characterized broadly SARS-CoV-2 neutralizing monoclonal antibody P4A2 was able to rescue thymic atrophy and restore the thymic maturation pathway of T-cells. Together, we report SARS-CoV-2-associated thymic atrophy resulting from impaired T-cell maturation pathway which may contribute to dyregulated T cell response during COVID-19.

Age-related transcript changes in type I interferon signaling in children and adolescents with long COVID.

SARS-CoV-2 typically causes mild symptoms in children, but evidence suggests that persistent immunopathological changes may lead to long COVID (LC). To explore the interplay between LC and innate immunity, we assessed the type I interferon (IFN-I) response in children and adolescents with LC symptoms (LC; n = 28). This was compared with age-matched SARS-CoV-2 recovered participants without LC symptoms (MC; n = 28) and healthy controls (HC; n = 18). We measured the mRNA expression of IFN-I (IFN-α/β/ε/ω), IFN-I receptor (IFNAR1/2), and ISGs (ISG15, ISG56, MxA, IFI27, BST2, LY6E, OAS1, OAS2, OAS3, and MDA5) in PBMCs collected 3-6 months after COVID-19. LC adolescents (12-17 years) had higher transcript levels of IFN-β, IFN-ε, and IFN-ω than HC, whereas LC children (6-11 years) had lower levels than HC. In adolescents, increased levels of IFN-α, IFN-β, and IFN-ω mRNAs were found in the LC group compared with MC, while lower levels were observed in LC children than MC. Adolescents with neurological symptoms had higher IFN-α/β mRNA levels than MC. LC and MC participants showed decreased expression of ISGs and IFNAR1, but increased expression of IFNAR2, than HC. Our results show age-related changes in the expression of transcripts involved in the IFN-I signaling pathway in children and adolescents with LC.

Characterization of immune responses and immunopathology in turkeys experimentally infected with clostridial dermatitis-producing strains of Clostridium septicum

Clostridium septicum is one of the major causative agents of clostridial dermatitis (CD), an emerging disease of turkeys, characterized by sudden deaths and necrotic dermatitis. Despite its economic burden on the poultry industry, the immunopathological changes and pathogen-specific immune responses are poorly characterized. Here, we used three strains of C. septicum, namely Str. A1, Str. B1 and Str. C1, isolated from CD field outbreaks, to experimentally infect turkeys to evaluate local (skin and muscle) and systemic (spleen) pathological and immunological responses. Results showed that while all three strains produced an acute disease, Str. A1 and B1 caused significantly higher mortality when compared to Str. C1. Gross and histopathology evaluation showed that birds infected with Str. A1 and B1 had severe inflammatory, edematous, granulomatous and necrotic lesions in the skin, muscle and spleen, while these lesions produced by Str. C1 were relatively less severe and mostly confined to skin and/or muscle. Immune gene expression in these tissues showed that Str. B1-infected birds had significantly higher expression of interleukin (IL)−1β, IL-6 and interferon (IFN)γ genes compared to uninfected control, suggesting a robust inflammatory response both locally as well as systemically. The transcription of IL-1β and IFNγ in the muscle or spleen of Str. A1-infected birds and IL-1β in the skin of Str. C1-infected group was also significantly higher than control. Additionally, Str. A1 or B1-infected groups also had significantly higher IL-4 transcription in these tissues, while birds infected with all three strains developed C. septicum-specific serum antibodies. Furthermore, splenic cellular immunophenotyping in the infected turkeys showed a marked reduction in CD4+ cells. Collectively, it can be inferred that host responses against C. septicum involve an acute inflammatory response along with antibody production and that the disease severity seem to depend on the strain of C. septicum involved in CD in turkeys.

Methodological aspects of anti-nuclear antibodies detection: EFLM, EASI, ICAP AND RAMLD recommendations

This is a review of international and Russian recommendation for the study of anti-nuclear antibodies (ANA) in autoimmune inflammatory rheumatic diseases (AIRD) and autoimmune liver diseases (ALD), including a description of the most important methodological aspects. The main purpose of laboratory diagnostics of AIRD and ALD is to obtain objective information about the presence and immunopathological changes, which is an important tool for early diagnosis, assessment of activity, severity, prognosis of the disease and the effectiveness of therapy. The positive results of ANA determination are the main laboratory markers of AIRD and ALD, being among the diagnostic criteria for diseases. The ‘gold standard’ and primary screening method for determining ANA in serum is the indirect immunofluorescence assay (IFA). Antigen-specific solid phase assays methods are used as confirmatory tests. Standardization of the ANA determination contributes for reducing the intra- and inter-laboratory variability of the results, helps to optimize the interaction between laboratory specialists and clinicians in matters of prescribing and clinical interpretation of ANA tests. Solving the problem of ANA detection standardization is important because of the growing number of laboratories performing these tests and an increased referring for this investigation from rheumatologists and another medical specialist.

Efficacy of artemether against toxocariasis in mice: parasitological and immunopathological changes in brain, liver, and lung

ABSTRACT Toxocariasis is a zoonosis that represents a serious threat to public health particularly in tropical and subtropical areas. Currently, albendazole, the most effective drug for treating visceral toxocariasis, shows moderate efficacy against the larvae in tissues and has some adverse effects. Artemether is an antiparasitic drug mainly used in the treatment of malaria and showed effectiveness against numerous helminthic infections. Besides, it possesses potent anti-inflammatory, antiapoptotic, antifibrotic, and neuroprotective properties. Thus, the study’s aim was to investigate artemether’s effects in comparison with albendazole on the therapeutic outcome of experimental toxocariasis. For this aim, 140 laboratory-bred mice were divided into four main groups: uninfected control, treatment control, albendazole-treated, and artemether-treated groups. The treatment regimens were started at the 15th dpi (early treatment), and at the 35th dpi (late treatment). The effectiveness of treatment was determined by brain larval count, histopathological, immunohistochemical, and biochemical examination. Artemether showed more effectiveness than albendazole in reducing brain larval counts, markers of brain injury including NF-κB, GFAP, and caspase-3, the diameter and number of hepatic granulomas, hepatic oxidative stress, hepatic IL-6, and TG2 mRNA, and pulmonary inflammation and fibrosis. The efficacy of artemether was the same when administered early or late in the infection. Finally, our findings illustrated that artemether might be a promising therapy for T. canis infection and it could be a good substitution for albendazole in toxocariasis treatment.

Studies on immunopathological changes induced by commercial IBD live vaccines in poultry birds

Intermediate plus live strain infectious bursal disease virus (IBDV) vaccines are used to control IBDV endemic infections in India. In the present study, immunopathological changes induced by commercial infectious bursal disease live vaccines with different immunization regimes were compared. A total of days old 108 Cobb broiler chicks were randomly divided into five groups with 24 chicks each in groups I, II, III and 18 chicks each in group IV and V. Group I served as control I (no immunization) and group II and III chicks were immunized with a single dose of vaccines 1 and 2 on 17th day of age (DOA), respectively. The group IV and V chicks were immunized with vaccines 1 and 2, respectively with primary dose on 17th DOA followed by booster dose on 24th DOA. Both intermediate plus live vaccines produced gross and histopathological lesions in lymphoid organs (bursa of Fabricius, thymus, spleen and caecal tonsils). Increased CD4 + , CD8 + T cells in affected bursa of Fabricius was evidenced by immunohistochemistry. Further, up-regulation in relative mRNA expression of IFN-γ, IL-1β and IL-6 were observed in bursa of Fabricius of treated birds, with maximum alteration particularly on 14th day post single immunization and 7th day post booster immunization. The findings suggest that single immunization regime on the 17th day of age showed immunization equivalent to booster immunization with lesser lesions, therefore, may be practiced and promoted in the field conditions for the better economic returns and animal welfare.

Retrospective analysis of the prevalence of diseases of the oral mucosa in the Volgograd region

The paper presents the results of a retrospective analysis of the prevalence of diseases of the oral mucosa. It is noted that the high prevalence of various ORS diseases is associated with a new coronavirus infection COVID-19 due to immunopathological changes in the patients body. It is known that patients with OOP diseases represent one of the most difficult groups of patients in dentistry. An increase in the frequency of occurrence of erosive-ulcerative lesions of the ROR was noted, which have different etiology and pathogenesis, while their clinical picture is quite similar. The study was carried out in the dental clinics of Volgograd clinical bases of the Department of Dentistry of the Institute of the NMFO FSBEI HE VolgGMU of the Ministry of Health of Russia. 2719 medical records of a dental patient (form 043y) were studied in the period 20192022. There was a significant dynamic growth, especially in 2022, of inflammatory-destructive pathologies of the COR, as well as the highest prevalence of COR pathologies in middle-aged people. A persistent increase in complicated cases with a generalized spread of pathological elements was revealed, which proves the relevance of searching for new methods for managing these patients.

Transcriptomic Profiling the Effects of Airway Exposure of Zinc Oxide and Silver Nanoparticles in Mouse Lungs

Consumers and manufacturers are exposed to nanosized zinc oxide (nZnO) and silver particles (nAg) via airways, but their biological effects are still not fully elucidated. To understand the immune effects, we exposed mice to 2, 10, or 50 μg of nZnO or nAg by oropharyngeal aspiration and analyzed the global gene expression profiles and immunopathological changes in the lungs after 1, 7, or 28 days. Our results show that the kinetics of responses varied in the lungs. Exposure to nZnO resulted in the highest accumulation of F4/80- and CD3-positive cells, and the largest number of differentially expressed genes (DEGs) were identified after day 1, while exposure to nAg caused peak responses at day 7. Additionally, nZnO mainly activated the innate immune responses leading to acute inflammation, whereas the nAg activated both innate and adaptive immune pathways, with long-lasting effects. This kinetic-profiling study provides an important data source to understand the cellular and molecular processes underlying nZnO- and nAg-induced transcriptomic changes, which lead to the characterization of the corresponding biological and toxicological effects of nZnO and nAg in the lungs. These findings could improve science-based hazard and risk assessment and the development of safe applications of engineered nanomaterials (ENMs), e.g., in biomedical applications.

Calcium homeostasis and certain aspects of its disturbances in juvenile idiopathic arthritis

Background. In the pathogenesis of juvenile idiopathic arthritis (JIA), the main role is played by immunopathological changes in the body with a loss of tolerance to the elements of own tissues; herewith, disorders of calcium and bone metabolism are very important. Such changes occur as a result of autoimmune inflammation, pharmacotherapy, and the influence of a number of other factors that negatively affect calcium homeostasis in the body. Purpose: to study the features of calcium homeostasis and certain aspects of its disorders with an assessment of the structural and functional state of bone tissue, taking into account clinical subtypes and disease activity. Material and methods. Sixty-two children with JIA aged 3.5 to 16 years were examined, of them 11 had systemic and 51 had oligo- and polyarthritis. There were determined serum concentrations of a total calcium using the Lachema test kit (Czech Republic), protein-bound and ultrafiltered fractions, content of inorganic phosphorus (with the generally accepted spectrophotometric method using the Cobas 6000 analyzer and test systems by Roche Diagnostics, Switzerland), the activity of total alkaline phosphatase and its isoenzymes (bone and intestinal) using the Lachema test system (Czech Republic). Ultrasonic osteometry of the calcaneal (trabecular) bone was performed on the Achilles device (Lunar, USA). Results. A significant decrease was found in the average concentration of total calcium, protein-bound calcium in systemic JIA and in high disease activity. The concentration of the ultrafiltered calcium fraction decreased only with high disease activity. The average concentration of inorganic phosphorus in children with oligo- and polyarthritis was within the normal range, while in systemic JIA it decreased. A significant decrease in the serum content of inorganic phosphorus, as well as in the activity of total alkaline phosphatase and its bone isoenzyme was detected in patients with high activity of systemic JIA. In patients with JIA (oligo-, polyarthritis) characterized by a slowly progressive rheumatic process, only the indicator of broadband ultrasound attenuation significantly changed during the first year of the disease, while the speed of ultrasound propagation and the index of bone tissue strength were not changed. In patients with a longer duration of the disease, all densitometric indicators decreased significantly. In the group of patients with systemic JIA and a rapidly progressive course, high activity of the disease that required a glucocorticoid therapy, a significant loss of bone mass was noted by the end of the first year of the disease. Conclusions. In JIA, there are changes in the concentration of total calcium and its protein-bound and ultrafiltered fractions in the blood serum, which indicate the tension of calcium-phosphorus metabolism and possible calcium deficiency in the body already at the early stages of the pathological process. A decrease in the activity of the alkaline phosphatase and its bone isoenzyme is associated with a violation of the structural and functional changes in the bone system of patients with JIA, which progresses with the duration of the disease. Patients with JIA require timely diagnosis and monitoring of calcium-phosphorus metabolism disorders with an assessment of the structural and functional state of the bone system for purposeful correction of comprehensive therapy due to the use of drugs in order to increase bone tissue regeneration, reduce the progression of osteopenia and osteoporosis, and preserve the health of the growing organism.

ВЛИЯНИЕ ПАРАЗИТАРНЫХ ПРОСТЕЙШИХ НА КИШЕЧНУЮ МИКРОБИОТУ ЭКСПЕРИМЕНТАЛЬНЫХ ЖИВОТНЫХ

There is relatively little information on the effect of probiotic supplements used in helminthiasis, and one can only guess how much probiotics can affect helminthiasis and associated inflammatory and immunopathological changes in the gastrointestinal tract, as well as how parasitosis can affect the properties of probiotic preparations. The aim of this study was to study the effect of Giardia and Cryptosporidium on the intestinal microbiota of experimental animals in the study of probiotics. In the intestinal microbiota of experimental mice with successfully integrated probiotic strains of Lactobacillus sakei and Lactococcus lactis, cryptosporidium and giardia, which may indicate the antagonistic effect of cryptosporidium and giardia did not find these strains after protozoal invasion against these strains. Key words: probiotics, cryptosporidium, giardia, microbiome.

Полиморфизм генов цитокинов, ассоциированных с инфекционным эндокардитом

Infectious endocarditis is a disease with the primary pathogen localization on the heart valves and the mural endocardium, occurring with the possible generalization of the septic process and the immunopathological changes that are very significant in the disease manifestation and course. Based on the fact that 30–50% of cases concerning infectious endocarditis develop without the obvious involvement of standard risk factors (invasive procedures or endovascular disorders), it can be assumed that molecular genetic factors are involved in the disease pathogenesis and its complications. There is reason to believe that the activation of inadequate inflammation in response to the microbial invasion may be due to polymorphism in the genes controlling the cytokine activity. However, the information available today on the various cytokines level and the gene polymorphism in various clinical variants of infectious endocarditis is very limited and commonly contradictory, which requires a deeper study of the pathogenetic association of infectious endocarditis with cytokine genetic defects. In this regard, the expansion of ideas concerning the of cytokine gene polymorphisms in the form of point mutations (SNP), capable of regulating the intensity of cytokine expression and their biological effects, will allow to predict the risk of infectious endocarditis, the severity of its course, the risk of possible complications, as well as the individual treatment tactics for patients. KEYWORDS: infectious endocarditis, clinical variants, complications, cytokines, cytokine genes, genetic polymorphism, pathogenesis, diagnosis. FOR CITATION: Samoylenko E.S., Kolesnikova N.V. Cytokine gene single nucleotide polymorphisms associated with infectious endocarditis. Russian Medical Inquiry. 2023;7(7) (in Russ.). DOI: 10.32364/2587-6821-2023-7-7-2.

Gastrointestinal Conditions in Rheumatoid Arthritis Patients

Rheumatoid arthritis (RA) is a serious medical and social problem, characterised by a steadily progressive disorganisation of the connective tissue, based on profound immunopathological changes with autoaggressive features. RA ranks first in terms of prevalence among inflammatory diseases of the joints. The social significance of this disease is determined not only by its high prevalence, but also by the great material damage caused to society, the patient and his family due to the high incapacity and early onset of disability. Steady progression of the pathological process despite the use of modern therapeutic methods results not only in significant functional insufficiency of the locomotor apparatus but also in the shortening of the patients' life span by 4-10 years and the increase of the death rate which exceeds that of the general population. The prognosis of RA patients with systemic manifestations is particularly unfavorable: generalized vasculitis, rheumatoid nodules, lymphoadenopathy, lung, heart, liver, kidney and other organs and systems are affected. Among the extra-articular manifestations of RA, gastrointestinal (GI) lesions are the least studied, although the most severe process, intestinal amyloidosis, is well known, occurring in 11% of patients and usually combined with amyloidosis of other internal organs.

The diminution and modulation role of water-soluble gallic acid-carboxymethyl chitosan conjugates against the induced nephrotoxicity with cisplatin

The toxicity of cisplatin (CDDP) toward the renal tubules and its severe effects on the proximal tubules limits its further use in cancer therapy. The current study was undertaken to evaluate the protective effects of gallic acid-grafted O-carboxymethyl chitosan (GA@CMCS) against nephrotoxicity induced by CDDP in rats. Renal injury was assessed in the GA@CMCS/CDDP-treated rats using kidney injury molecule-1 (KIM-1). Moreover, the levels of reduced glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) were measured. The comet assay was performed to measure the DNA damage. The renoprotective activity of GA@CMCS was supported by histo- and immuno-pathological studies of the kidney. GA@CMCS significantly normalized the increases in kidney homogenate of KIM-1, MDA, and NO-induced by CDDP and significantly increased GSH as compared with the CDDP group. GA@CMCS also significantly protects rat kidneys from CDDP-induced histo- and immuno-pathological changes. Both biochemical findings and histo- and immuno-pathological evidence showed the renoprotective potential of GA@CMCS against CDDP-induced oxidative stress, inflammation, and renal dysfunction in rats. In conclusion, GA@CMCS has been shown to mitigate the nephrotoxicity impact of CDDP in cancer therapy.

E3 ligase RNF5 inhibits type I interferon response in herpes simplex virus keratitis through the STING/IRF3 signaling pathway.

Herpes simplex keratitis (HSK), caused by the herpes simplex virus 1 (HSV-1), is a major blinding disease in developed countries. HSV-1 can remain latent in the host for life and cannot be eradicated. The infection causes the secretion of various cytokines and aggregation of inflammatory cells. In the early stage of inflammation, mainly neutrophils infiltrate the cornea, and CD4+ T cells mediate the immunopathological changes in herpetic stromal keratitis in the subsequent progression. The STING/IRF3-mediated type I interferon (IFN) response can effectively inhibit viral replication and control infection, but the activity of STING is affected by various ubiquitination modifications. In this study, we found that the expression of RNF5 was elevated in corneal tissues and corneal epithelial cells after infection with HSV-1. Immunofluorescence staining confirmed that RNF5 was mainly expressed in the corneal epithelial layer. We silenced and overexpressed RNF5 expression in corneal epithelial cells and then inoculated them with HSV-1. We found that the expressions of STING, p-IRF3, p-TBK1, and IFN-β mRNA increased after RNF5 silencing. The opposite results were obtained after RNF5 overexpression. We also used siRNA to silence RNF5 in the mouse cornea and then established the HSK model. Compared with the siRNA-control group, the siRNA-RNF5 group showed significantly improved corneal inflammation, reduced clinical scores and tear virus titers, and significantly increased corneal IFN-β expression. In addition, the expressions of the proinflammatory cytokines IL-6 and TNF-α in the corneal tissue were significantly decreased, indicating that RNF5 silencing could effectively promote IFN-I expression, inhibit virus replication, alleviate inflammation, and reduce corneal inflammatory damage. In summary, our results suggest that RNF5 limits the type I IFN antiviral response in HSV corneal epithelitis by inhibiting STING/IRF3 signaling.

SARS-CoV-2 Vaccines: The Mucosal Immunity Imperative

SARS-CoV-2 Vaccines: The Mucosal Immunity Imperative

Accelerated alveolar bone loss in a mouse model of inflammatory bowel disease and its relationship with intestinal inflammation.

Bone loss is a common complication of inflammatory bowel disease (IBD); however, few studies have focused on alveolar bone loss (ABL) in IBD. Herein, we systematically observed ABL in an interleukin (IL)-10 knockout (IL-10-/- ) mouse model of IBD and explored the possible mechanisms. IL-10-/- and age-matched wild-type (WT) male mice were sacrificed every 2 weeks from 12 to 24weeks of age. ABL was determined by microcomputed tomography. Periodontal and intestinal inflammation were evaluated using histological grading and inflammatory factor expression levels. Intestinal barrier integrity and cytokine levels in serum were examined by immunofluorescence and enzyme-linked immunosorbent assays, respectively. The expression of macrophage phenotype markers, including inducible nitric oxide synthase (iNOS), arginase-1 (Arg-1), and bone metabolic markers, including osteoprotegerin, receptor activator of nuclear factor-κB ligand (RANKL), were measured by immunohistochemistry. The macrophage phenotype in the periodontium was also examined by real-time quantitative polymerase chain reaction. Compared with WT mice, IL-10-/- mice exhibited significant ABL from 18weeks of age. However, no significant differences were observed in the periodontium between the two groups in either histopathological scores or inflammatory factor levels. In the colon and ileum, these measurements significantly increased in IL-10-/- mice from 12 and 14weeks, respectively. Correlation analysis also revealed that ABL in IL-10-/- mice was positively correlated with intestinal inflammation. Furthermore, IL-10-/- mice showed a destroyed intestinal barrier and higher serum levels of inflammatory factors. In both the intestine and periodontium, higher iNOS and lower Arg-1 levels, along with an increase in RANKL expression in the periodontium, were examined in IL-10-/- mice. An accelerated ABL spontaneously occurred in IL-10-/- mice and was correlated more with inflammation of the intestine than periodontium. Immunopathological changes may be the potential cause of abnormal alveolar bone metabolism.

Immunopathological Changes Post-Infection with Enterobacter cloacae in Rabbits.

Nosocomial infections have serious effects on health conditions in humans and animals. The present study aimed to investigate the pathogenesis of Enterobacter cloacae post intraperitoneal inoculation in rabbits to investigate the immunological and possible pathological effects. A total of 42 rabbits were randomly divided into two equal groups (n=21). The first group was inoculated with 3×108 CFU/ml of the virulent isolate of E. cloacae intraperitoneally (IP), while the second group was injected IP with phosphate buffer saline and considered a control negative group. The animals were sacrificed at different time post-infection at 48/72 h, and at day 7 post-bacterial inoculation. The results revealed a significant increase in the concentration of TNF-α, especially in the infected groups. In addition, there were different pathological lesions in different organs of animals, mainly in the infected groups, which represents by vascular congestion and edema with polymorphoneutrophiles infiltration in the lungs, kidneys, and heart. This study is considered the first trial which aimed to observe the pathological changes of E. cloacae in vital organs in rabbits.

Immunopathological changes in case of the diabetes of the first type. The impact of the mother’s diabetes of the first type on the emryogenesis and fetogenesis of the fetus (Literature review, part II)

In the following article we have presented main risk factors of the development of the Diabetes Mellitus of the I type, as well as modern statistical data towards its correlation in a structure of the disease. We have revealed main markers of the disease, connected with the HLA system. We have also considered leading links in the pathogenesis of immunodeficiency development in case of patients with the Diabetes Mellitus of the I type relatively to the duration of the disease, presence of vascular complications as well as number of insulin units per day. We have provided clear criteria towards changes in the T-lymphocytes populations, what is prescribing changes in the helper-suppressor ratio. In addition, we have postulated that the autoimmune disorders, which are typical for the Diabetes Mellitus of the I type (DM of the I type) are leading to the increase in a number of apoptotically alteredd forms of T-lymphocytes, what is contributing to the deeping of changes in the immune system. Authors have studied main features of the interleukin-producing activity in case of patients with the DM of the I type. Namely: increased number of pro-inflammatory interleukins on the background of decrease of anti-inflammatory ones. The precise analysis has revealed, that there are circulating immune complexes in the blood of patients with DM of the I type, which are leading microcirculation’ disorders. The alterations, that were postulated and described relatively to the organism of patients with DM of the I type, are indicating deep disorders in the immune system and the morphological features of the thymus has to be studied, as far as the thymus as a central organ of the immunogenesis in case of fetuses from mothers, who are suffering from the DM of thr I type, in the aim of development of immunodeficiency in patients.
 Alongside with the description of changes in the immune system in case of patients with the DM of the I type, in the following article we have provided a scientific views on changes in the embrion- and fetogenesis of the fetus under the influence of mother’s DM of the I type. In addition, we have described morphological features of the placenta structure in case of this pathology, as well as pathomorphological changes in the strucutre of internal organs of fetus under the influence of this pathology in the mother’s organism. It was postulated, that in case of children, who were born from mothers, who are suffering from the DM of the I type, there is a syndrome of diabetic feto- and embryopathy, which is developing and leading to the poliorganic failure in the subsequent ontogenesis.

Immunophenotypical and pathological changes in dogs experimentally infected with Ehrlichia canis.

Canine monocytic ehrlichiosis (CME) is one of the most important tick-borne diseases worldwide, with multisystemic presentations. Immune dysregulation has been proposed as the primary mechanism involved in its pathogenesis and in tissue injury in dogs with CME. Experimental infection of German Shepherd dogs in the present study demonstrated that CME caused marked pathological changes in their lymph nodes and spleen, and also gave rise to mononuclear infiltration in organs and tissues. Immunophenotyping of cells in lymph nodes, spleen and injured tissues highlighted differences in lymphocyte subsets, local expression of immunoglobulin subclasses and MHCII molecules between infected and control dogs. These findings suggest that the immunophenotypic and immunopathological changes in dogs with acute experimental CME are related to Th1 bias and compartmentalized immune response.