Vol 20, No 4 (2017)

The differentiation and protective capacity of antigen-specific T-cells are regulated by both positive and negative signals. Molecules of the B 7/CD 28 family are very important for regulating T-cell activation and peripheral tolerance. In particular, PD-1, CTLA-4 and other co-inhibitory molecules play an active role in dampening of excessive immune activation which is critical for successful clearance of a pathogen without harm to the host. These co-inhibitory molecules (immunological checkpoints) are essential for inducible Treg differentiation and function. On the other hand, overexpression of co-inhibitory molecules can lead to T-cell exhaustion, an adaptive property that occurs in T-cells due to persistent systemic antigen exposure. Exhausted T-cells are described as effector T-cells with decreased cytokine expression and effector function. Here, we review a critical role of co-inhibitory molecules which they play in immunopathogenesis of four immunological syndromes: allergy, autoimmune diseases, chronic infection, and cancer. Reversal of exhausted T-cells by blocking co-inhibitory pathways has become an important area due to its therapeutic applications in oncology and chronic viral infections.

The formation of multimolecular complex: inflammasome is a platform for caspases’ activation, which process proinflammatory cytokines into biologically active forms (IL­1 and IL­18). Their secretion initiate and maintain the inflammation. Inflammasome activation is able to trigger the pyroptosis in the infected host cells in order to eliminate microbial pathogens.

Electrophoretically and immunologically homogeneous IgG preparations were isolated from blood plasma of 18 patients with schizophrenia (SHZ) and 14 healthy donors by affinity chromatography on Protein G-Sepharose with subsequent high-performance gel-filtration. H₂O₂-dependent peroxidase and H₂O₂-independent oxidoreductase activities of polyclonal IgG of SHZ patients and healthy donors in the oxidation of 3,3’-diaminobenzidine were compared for the first time. All IgG antibodies of SHZ patients and healthy donors possess these activities, but the apparent k_cat values varied in a very wide range (16,2-355,8 min^–1). The average oxidation rates of the substrate in the presence of H₂O₂ from the plasma of SHZ patients and healthy donors were 1,3-1,5 times higher than in the absence of H₂O₂. The difference between the average peroxidase (1,8 times) and oxidoreductases (1,5 times) activities of IgG from blood plasma of SHZ patients and healthy donors was statistically significant (p = 0,008). The correlation coefficient of oxidoreductase and peroxidase activities of antibodies of patients with SHZ was significantly higher (0,664) than for healthy donors (0,27). A possible biological role and the nature of abzymes origin with oxidoreductase functions are discussed. The blood of healthy donors and patients with various autoimmune diseases usually contains abzymes with amylase and ATPase activities. In the case of 18 patients with SHZ amylase activity was detected only for one IgG preparation, but all 18 IgGs were inactive in the hydrolysis of ATP.

The aim of this study was to evaluate the release of myeloperoxidase from the neutrophils and lactoperoxidase from the salivary glands into the oral liquid after oral-buccal provocative tests with components of dental materials to diagnose hypersensitivity to them in patients with intolerance to dental materials. The study group consisted of 24 patients with intolerance to dental materials. Patients underwent an oral-buccal provocative test with 0.001 % solution of metal salts: NiCl₂, CrCl₃, CoCl₂. It was found that an increase in the level of peroxidase activity in the oral fluid was observed in patients with intolerance to dental materials after an oral-buccal provocative test, but not in patients of the control group. It was shown that the oral-buccal provocation test with a solution of metal salts in patients with intolerance to dental materials after the removal of prosthetic constructions caused the release of myeloperoxidase from neutrophils in the oral fluid. The increase in the total level of peroxidase activity in the oral fluid was due to myeloperoxidase, but not lactoperoxidase. The method for determining the total oral peroxidase activity in a tetramethyl benzidine test can be used to detect intolerance to dental materials due to hyperreactivity of neutrophils.