PATHOGENETIC MECHANISMS OF DEVELOPING IMPAIRED INNATE AND ADAPTIVE IMMUNITY IN SEPSIS

Abstract

The objective of this review was to highlight the problem of sepsis, the relevance of which is determined by the growing number of patients, the complexity of pathogenesis, and the difficulty of early diagnosis. Sepsis is a life-threatening severe dysfunction of internal organs caused by an infectious agent and occurring as a result of a complex interplay between proinflammatory and anti-inflammatory processes that can lead to multiple organ failure and death. This condition holds one of the leading places in morbidity and high mortality in surgical and intensive care units, and its prevalence has continued to steadily increase over the past years, especially among groups of patients with chronic diseases and weakened immunity. At different stages of pathogenesis, immune mechanisms act as both a generator of damage reactions and the main components of the body's defense reactions. Sepsis begins with an exuberant inflammatory reaction, which can last for several days, and then pass into a more protracted immunosuppressive period, with the outcome largely depending on the patient's immune system. The article focuses on understanding the role of developing disorders of innate and adaptive immunity in the pathogenesis of sepsis, their manifestations, mechanisms of immune dysfunction in septic conditions leading to impaired immune response. Bacteria that cause sepsis overcome the protective mechanisms of human immunity, which leads to the development of acute bacteremia, while the immunosuppression caused by pathogens leads to generalization of the process. Prominent bacteremia, increasing endotoxinemia due to generalization can lead to excessive activation of inflammatory, anti-inflammatory reactions and uncontrolled release of inflammatory mediators, damage to the body's defense mechanisms, particularly, depletion of T cells, decreased expression of human leukocyte antigen (HLA)-DR on monocytes and induced uncontrolled apoptosis of neutrophils and adaptive immune cells. This leads to a worsening of sepsis course and further aggravation of immune homeostasis disorders as well as continuing enhancement of the systemic inflammatory response. Therefore, a deeper understanding of the immunological aspects of sepsis pathogenesis, which are behind the development and progression of this condition, is becoming an important part of clinical practice and is of great importance for its timely identification, improvement of treatment strategies, increase in patient favorable outcomes and lowering related mortality.