About the institute

The Institute of Immunology was established in 1992. The constitution of the independent institute resulted from an intensive development of immunology and from a subsequent need to include this subject into those regularly taught in the Faculty of Medicine. The institute now regularly delivers lectures and holds practical lessons not only for medical students, but also for students of other specialisations. Moreover, the teaching is held both in the Slovak and in the English language. The new situation required providing students with textbooks; now, these are available in both languages and the Dictionary of Immunology was even translated into French and German languages, respectively.

Research has also become an inherent part of working activities in the institute. The immunogenetics of the major histocompatibility complex in man (HLA), the immunogenetics of cytokines supplemented by studies of inflammatory markers in the induction and development of autoimmune, cardiovascular, and lung diseases represent the major subjects of interest in recent years. Especially a role of these genes in induction and development of autoimmune diseases and cardiovascular disorders has been studied. The research activity is performed in the frame of national and international grants.

The teachers are active also outside of the Faculty of Medicine. Some of them are members of scientific boards; they work in editorial boards of national and international journals, in grant agencies, are members of boards of the Slovak Immunology Society or are active in other fields of science.

The specialisation of the institute:

- Immunology

- Immunogenetics

Current techniques running in the institute:

- Techniques of the molecular genetics for the determination of gene polymorphisms of the HLA complex and cytokines (PCR-SSP, PCR-RFLP, sequencing, ...)

- Techniques for the evaluation of soluble and membrane-bound molecules such as cytokines, acute phase proteins and membrane antigens (Flow cytomix, multiplex analysis, flow cytometry)

- Detection of antibodies against HLA- a MICA-antigens by multiplex analysis to establish a degree of rejection mechanisms following kidney transplantations

- Detection of new inflammatory markers by ELISA

Research activities:

- A population-genetic analysis of the Slovak population on occurrence rates of HLA alleles and polymorphisms of cytokine genes

- Studies on HLA, cytokine and other gene associations with selected autoimmune and other immune-related diseases (Type I diabetes mellitus, psoriasis, pemphigus vulgaris, juvenile idiopathic arthritis, asthma bronchiale, coeliac disease, coronary heart disease, urinary tract infections, etc.) in the Slovak population

- Studies on the role of inflammation in the pathogenesis of various diseases

- Studies on the imunopathogenesis of sepsis and heart stroke

- Studies on the role of HLA-G in a foetus tolerance

- Studies on the role of NK cells in GvH reaction

Scientific projects and grants

Research and scientific activity:

The main focus of research:

· Immunogenetic predisposition, the role of HLA alleles, cytokine and other gene polymorphisms and mutations in the immunopathogenesis of complex diseases

· The role of systemic inflammation of infectious and non-infectious origin as a key factor in the development and course of diseases, early diagnosis and their monitoring

· The role of cytokines, chemokines and other modern markers in the fibrotic process of lung diseases. Efforts towards an immunological classification of diffuse parenchymal lung diseases

· The importance of these biomarkers in improving the diagnosis, differential diagnosis and prognosis of patients

· Prognostic value of neuroimmunomodulation in oncology

In order to achieve the scientific goals, we cooperate with several institutions in Bratislava and other places in Slovakia, as well as the Institute of Immunology of the Faculty of Medicine in Olomouc, other workplaces in the Czech Republic and, most recently, in Israel and Canada

Diseases and pathological conditions studied at our institute:

1. Alzheimer's disease

Alzheimer's disease (AD) is the most common cause of dementia in the elderly population. It is caused by a progressive neurodegenerative process, which is clinically manifested by the gradual decline of cognitive and intellectual functions. Despite worldwide efforts, the etiopathogenesis of AD is not fully understood and the therapeutical options are only limited. It is known that genetic factors in cooperation with other factors are involved in the development of both early-onset (familial) and late-onset (sporadic) forms of AD.

· At our institute, we analyze the influence of genes with a function in the immune system on the risk of developing AD. In cooperation with clinical departments and facilities (Department of Psychiatry, I. and II. Department of Neurology UNB, Centrum Memory, n.o.) we created a bank of DNA and plasma samples of patients with AD as well as control persons of comparable age. We use the samples from this bank to investigate genetic, but also some non-genetic factors that can contribute to the development, prediction, or monitoring of the sporadic form of AD. Non-coding RNA molecules participating in the regulation of gene expression also play an important role in the process of neurodegeneration.

· We aim at identifying biomarkers of neurodegeneration in the plasma of patients with AD (as part of a grant task together with the Neuroimmunology Institute of the Slovak Academy of Sciences).

2. Chronic lung diseases

For more than 10 years, the institute has been devoted to the study of immunopathogenesis and the search for modern markers of inflammation and the improvement of the differential diagnosis of diffuse parenchymal lung diseases (DPLD). DPLD represents a group of more than 200 different diseases, the pathogenesis of which is often unknown and the diagnosis problematic. Our goals in this area are as follows:

· Efforts to improve diagnosis and differential diagnosis of diffuse parenchymal lung diseases using modern markers of inflammation (TREM-1, TREM-2, HMGB1, cytokines, chemokines, ...) and fibrosis (CX3CL1, ...). As for TREM molecules, we investigate their expression on CD14+ cells in BAL fluid together with other cells and inflammatory parameters using a flow cytometer, as well as their soluble form sTREM-1, sTREM-2 using the ELISA method. The advantage of this approach is the examination of markers directly in the focus of the pathological process.

· Efforts to understand the molecular mechanisms of progressive fibrotic processes (idiopathic pulmonary fibrosis, chronic form of hypersensitivity pneumonitis, fibrotic stage of pulmonary sarcoidosis) by analyzing CX3CL1 molecules, ADAM17 enzyme, their ratio as well as IGF2R/CD222 and its soluble form sIGF2R. We analyze IGF2R/CD222, the mechanism of its release under pathological circumstances and also its soluble form sIGF2R. The results demonstrate a specific mechanism of IGF2R release in progressive fibrotic processes within diffuse parenchymal lung diseases and have not been demonstrated in any other work to date.

· The quest for an immunological classification of diffuse parenchymal lung diseases, which has been lacking until now.

· To achieve these goals, we cooperate with the National Institute of Pulmonary Diseases and Thoracic Surgery in Vyšné Hágy, with the Department of Pneumology and Phthisiology of the Faculty of Medicine of the Comenius University and University Hospital in Bratislava, the laboratory of immunology Medirex, Ltd., and the Institute of Molecular Biology of the Slovak Academy of Sciences. In asthma bronchiale research, we previously cooperated with allergology centers in Nitra, Martin and Trenčín.

· We published the results of our research in several papers, two of which (Suchankova et al., 2013; Bucova et al., 2015) received Global Medical Discovery and World Biomedical Frontiers awards for their innovative approach and potential therapeutic impact in the future.

3. Brain tumors. The role of immunity and inflammation in the pathogenesis of gliomas

Gliomas are among the most common brain tumors, and their worst form, glioblastoma multiforme (GBM), has a very poor prognosis; patients live an average of 15 months. What influences the tumor process is the state of adaptive specific cell-mediated immunity and the presence of inflammation. Therefore, the goals of our research are:

· Study of modern inflammatory markers HMGB1, TREM-1, TREM-2, cytokines, chemokines, sHLA-G, gene polymorphisms, vitamin D and other factors that influence inflammation and may have significance in immunopathogenesis, diagnosis, differential diagnosis and prognosis of patients with gliomas.

· Study of modern immune markers in patients with gliomas.

· Immunohistochemical examination of tumor samples - tissues are obtained after the histopathological examination of the tumor samples, that is, we utilize remains after the diagnosis was established.

· We are successful thanks to the cooperation with the Department of Neurosurgery of the Faculty of Medicine of the Comenius University and University Hospital in Bratislava, and laboratories Medirex, Ltd., and Cytopathos, Ltd.

· We thank the League against Cancer for their financial support.

4. Immunopathogenesis of sepsis, the search for an early immunomarker to differentiate SIRS from sepsis and to monitor sepsis

Sepsis is a systemic inflammation of infectious origin, characterized by a failure of regulatory mechanisms, the development of metabolic disturbancies and, in the case of late diagnosis, the development of septic shock with a high mortality rate (45-70%). Patients' lives are threatened at an early stage by an exaggerated inflammatory response and later by the development of immunosuppression and even immunoparalysis, which results in the development of polymicrobial sepsis. Research objectives:

· The main goal is to find a marker/combination of markers that would help distinguish non-infectious SIRS from infectious sepsis, which would improve therapy as well as patient survival.

· Study of immune markers and modern markers of inflammation HMGB1, expression of TREM-1, TREM-2, sTREM-1, sTREM-2, PCT, presepsin, CX3CL1, cytokines, chemokines, sHLA-G, gene polymorphisms, vitamin D and other factors and their significance in early diagnosis of sepsis and its differentiation from SIRS, in the prognosis of patients with SIRS/sepsis and also their correlation with survival.

· We would like to thank the Department of Anesthesiology and Intensive Medicine of the Faculty of Medicine of the Comenius University and University Hospital in Bratislava (Anna Dobišová, MD.) and Medirex, Ltd. for their cooperation.

5. Autoimmune diseases and other pathological inflammatory conditions

The long-term content of the scientific and research activities at our institute is also the investigation of the role of gene polymorphisms in the predisposition to the development of various complex immune-related diseases such as multiple sclerosis, psoriasis vulgaris, pemphigus vulgaris, Crohn's disease, type 1 diabetes mellitus and acute pyelonephritis in children.

· We are focusing on variants (single nucleotide polymorphisms, mutations) in the genes for cytokines, chemokines and their receptors, membrane and adhesive molecules, and most recently also adipokines - cytokines formed by adipose tissue.

· For a long time, we have also been dedicated to the examination of HLA alleles and their association with the aforementioned diseases.

· In addition to the contribution of gene polymorphisms to the risk of developing the aforementioned diseases, we have been also examining their mutual interactions, interactions with sex and other risk factors, and their impact on the severity and course of the diseases and other clinical parameters. For this purpose, we established successful cooperation with the I. and II. Departments of Neurology and the Department of Dermatovenerology of the Faculty of Medicine of the Comenius University and University Hospital in Bratislava, the Department of Pediatrics of the Faculty of Medicine of the Comenius University, the Institute of Clinical Biochemistry and the Clinic of Neurology, Jessenius Faculty of Medicine and University Hospital in Martin, the National Institute of Endocrinology and Diabetology in Ľubochňa, as well as the Institute of Immunology of the University Hospital in Essen.

6. Breast, head, neck and bladder tumors

The immune system is also regulated by components of the nervous system.

· Our research is focused on the prognostic value of markers of sympathico-vagal balance on the course of cancer and the mutual connection between the activity of the vagus nerve and tumor-associated immunity.

· The goal is to investigate the relationships between the sympathico-vagal balance determined by heart rate variability (HRV) and immune markers in tumors and their correlation with the course of the malignant disease. It is a new starting project in cooperation with OUSA, University Hospital Bratislava - Petržalka, Antolská and Hospital of St. Cyril and Method in Bratislava.

7. Immunogenetic determination and the role of low-grade chronic inflammation in the pathogenesis of cardiovascular diseases (ischemic heart disease, angina pectoris, myocardial infarction, hypertension)

Low-grade chronic inflammation also plays an important role in the pathogenesis of atherosclerosis and cardiovascular diseases. Our research goals in this area have been:

· Study of gene polymorphism of inflammatory markers (MCP-1, TREM-1, ...) and soluble markers hsCRP, cytokines, chemokines (MCP-1, ...) in the immunopathogenesis of cardiovascular diseases.

We have obtained interesting results thanks to the cooperation with II. Department of the Internal Medicine of the Faculty of Medicine, Comenius University in Bratislava (assoc. prof. Ján Lietava, MD., CSc.), and the Laboratory of Immunogenetics at the Institute of Immunology of the Faculty of Medicine in Olomouc (prof. Martin Petřek, MD., DrSc. and assoc. prof. František Mrázek, MD., PhD.).

8. Transplantation immunology

The Institute of Immunology was at the birth of transplant immunology in Slovakia::

· We introduced methodology for the determination of transplantation antigens (HLA), namely serological, cellular and eventually genetic method. We were directly involved in the selection of donor-recipient pairs for kidney transplantations and later bone marrow transplantations (BMT) in cooperation with the clinics that performed them (Department of Urology, Department of Hematology and Transfusiology). For this activity, the institute won the Award of the Ministry of Health.

· We also took part in determining the degree of chimerism after the BMT. We also participated in the research on the issue and participated in international cooperation to increase the level of typing quality.

· Later, when the transplantation program was taken over by healthcare facilities, we continued in this area of research mainly by determining antibodies against MICA-antigens, which belong to the weak transplant antigens, and determining whether these have an effect on graft rejection. The projects were implemented in cooperation with the National Transplantation Organization, the Department of Urology, and the Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry of the Faculty of Medicine in Bratislava.

· The methods introduced for the HLA typing have been eventually used also in other research areas, such as immunogenetics of autoimmune diseases.

Grant projects:

APVV-21-0197: Investigation of the impact of stress on the course of cancer (project leader: Božena Smolková, MSc., PhD., co-investigators: Ľuba Hunáková, MA., PhD., assoc. prof. Mária Bucová, MD., PhD., extraordinary prof.)

VEGA 1/0090/22: Neuroimmunological aspects of cancer (project leader: Ľuba Hunáková, MA., PhD.)

VEGA 1/0758/20: Diffuse parenchymal lung diseases - inflammation, immunologic mechanisms and determination of novel markers for diagnosis and differential diagnosis (project leader: assoc. prof. Mária Bucová, MD., PhD., extraordinary prof.)

VEGA 1/0738/20: Biomarkers of inflammation in patients with Alzheimer’s disease (project leader: assoc. prof. Ivana Shawkatová, MSc., PhD.)

VEGA 1/0136/18: Diagnostic potential of monitoring fluorescent characteristics of body fluids and analysis of extracellular microvesicles in cancer diseases of the urogenital system (project leader: Milan Zvarík, MA., PhD.; co-investigator: Ľuba Hunáková, MA., PhD.)

VEGA 1/0217/17: TREM-1, TREM-2 tests as new diagnostic and differential-diagnostic tests for sarcoidosis and other diffuse parenchymal lung diseases. Attempt at immunological classification of pulmonary diseases (project leader: assoc. prof. Mária Bucová, MD., PhD. extraordinary prof.)

VEGA 1/0240/16: Immunogenetic markers in Slovak patients with Alzheimer´s disease (project leader: assoc. prof. Ivana Shawkatová, MSc., PhD.)

VEGA 1/0833/13: Immunogenetic determination and inflammation in chronic lung diseases (project leader: assoc. prof. Mária Bucová, MD., PhD. extraordinary prof.)

VEGA 1/0810/12: Immunogenetic determination of the response to biologic therapy in multiple sclerosis patients (project leader: prof. Milan Buc, MD., DrSc.)

KEGA 012UK-4/2020: Základná a klinická imunológia (Basic and Clinical Immunology) (project leader: prof. Milan Buc, MD., DrSc.)

UK/245/2022 (Agáta Očenášová, MSc.)

UK/16/2022 (Dominika Radošinská, MSc.)

UK/285/2021 (Kristína Klučková, MD.)

UK/374/2021 (Eszter Zsemlye, MSc.)

UK/299/2019 (Kristína Klučková, MD.)

UK/252/2018 (Kristína Klučková, MD.)

UK/279/2018 (Michaela Olejárová, MD.)

UK/346/2017 (Michaela Olejárová, MD.)

UK/375/2017 (Lenka Maruščáková, MD.)

UK/301/2017 (Beáta Gajdošechová, MSc.)

UK/451/2016 (Michaela Olejárová, MD.)

UK/202/2016 (Beáta Gajdošechová, MSc.)

Personnel and contacts

Head of the institute

assoc. prof. Mária Bucová, MD., PhD., extraordinary prof.

tel.: +421 2 9011 9351

e-mail: maria.bucova@fmed.uniba.sk, imunologia.prednostafmed.uniba.sk

Deputy head

Magda Suchánková, MD., PhD.

tel.: +421 2 9011 9664

e-mail: magda.suchankova@fmed.uniba.sk

Secretary of the institute

assoc. prof. Vladimíra Ďurmanová, MA., PhD.

tel.: +421 2 9011 9887

e-mail: vladimira.durmanova@fmed.uniba.sk

Office girl

Lenka Zmijová

tel. +421 2 9011 9450

e-mail: lenka.zmijovafmed.uniba.sk

Professors

prof. Milan Buc, MD., DSc. (milan.bucfmed.uniba.sk; +421 2 9011 9398)

assoc. prof. Mária Bucová, MD., PhD., extraordinary prof. (maria.bucovafmed.uniba.sk; +421 2 9011 9351)

Associate professors

assoc. prof. Vladimíra Ďurmanová, MA., PhD. (vladimira.durmanovafmed.uniba.sk; +421 2 9011 9887)

assoc. prof. Ivana Shawkatová, M.Sc., PhD. (ivana.shawkatovafmed.uniba.sk; +421 2 9011 9578)

Lecturers and assistant lecturers

Monika Homolová, MD., PhD. (monika.homolovafmed.uniba.sk; +421 2 9011 9820)

Juraj Javor, MD., PhD. (juraj.javorfmed.uniba.sk; +421 2 9011 9582)

Michaela Kopčová, MD., PhD. (michaela.kopcovafmed.uniba.sk; +421 2 9011 9664)

Zuzana Párnická, MD., PhD. (zuzana.parnickafmed.uniba.sk; +421 2 9011 9819)

Magda Suchánková, MD., PhD. (magda.suchankovafmed.uniba.sk; +421 2 9011 9664)

Research employees

Ľuba Hunáková, MA., PhD. (luba.hunakova@fmed.uniba.sk; +421 2 9011 9943)

Other employees

Adam Kostič (adam.kosticfmed.uniba.sk; +421 2 9011 9578)

Zuzana Nürnberger (imunologia.laboratoriumfmed.uniba.sk; +421 2 9011 9314)

MSc. Daniela Reháková (imunologia.laboratoriumfmed.uniba.sk; +421 2 9011 9204)

Mária Reinoldová (imunologia.laboratoriumfmed.uniba.sk; +421 2 9011 9204)

Peter Sýkora (+421 2 9011 9519)

Beáta Tolvaj (imunologia.laboratoriumfmed.uniba.sk; +421 2 9011 9204)

Beata Tóthová (imunologia.laboratoriumfmed.uniba.sk; +421 2 9011 9204)

PhD students

Michaela Kardohelyová, M.Sc. (kardohelyova1uniba.sk;+421 2 9011 9820)

Iveta Mikolášková, M.Sc. (mikolaskova6uniba.sk; +421 2 9011 9820)

Agáta Očenášová, M.Sc. (agata.ocenasovafmed.uniba.sk; +421 2 9011 9664)

Eszter Zsemlye, M.Sc. (eszter.zsemlyefmed.uniba.sk; +421 2 9011 9664)

Anna Dobišová, MD. (anna.dobisovafmed.uniba.sk)

Eva Žůrková, MD. (eva.zurkovafmed.uniba.sk)