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PhD. Topics

Institute of Neuroimmunology

Markers of functional immune response of T lymphocytes suitable for characterization of primary and secondary immunodeficiencies
PhD. program
Molecular biology
Name of the supervisor
Mgr. Branislav Kováčech, PhD.
Receiving school
Faculty of Natural Sciences Comenius University in Bratislava
Primary and secondary immunodeficiencies are manifested by heterogeneous symptoms of systemic or organ-specific character, ranging from difficulties to resolve infections to autoimmune, autoinflammatory or allergic disorders. The proper evaluation of the status of the juvenile immune system is hindered by its high complexity, flexibility and dynamics, and high inter-individual variability augmented by the young age, which greatly influence prognosis and selection of an appropriate therapeutic approach. T cells are the principal regulators and effectors of the establishment and maintenance of the immune responses and memory, and coordinate other immune cells. Current clinical praxis does not provide sufficient characteristics of a juvenile immune system, and there is a need for more comprehensive evaluation of effector and memory functionalities of T cells. The main aim of the project is to setup robust methods for functional assessment of T cell responsiveness to activation stimuli that will add the required characteristics of the juvenile immunodeficiencies for identification of patients at risk for severe infections requiring a personalized care (immuno-substitutional or prophylactic therapy, transplantation of HSCs). The tests would complement examinations currently used in the clinics in Slovakia.
The project employs stimulation of T cells in the whole blood by mitogens and specific antigens, evaluation of the activation of the individual CD4+ subsets by flow cytometry and cytokine levels by multiplex assays. The patients will be recruited and diagnosed by the ambulance of clinical immunology of the National Institute of Children’s Diseases in Bratislava, Slovakia. The cohort will include primary and secondary immunodeficiencies (22q11.2DS, CVID, SCID/CID, positive TREC/KREC, transitory juvenile hypogammaglobulinemia, rheumatoid diseases, IBD, post-transplantation cases) and compared with healthy controls. We will attempt to compile a set of relatively simple and robust flow cytometry tests suitable for a comprehensive diagnosis.