Goodbye SIRS? Innate, trained and adaptive immunity and pathogenesis of organ dysfunction

Area of Science:

• Immunology
• Critical Care Medicine
• Pathophysiology

Background:

• The Sepsis-3 criteria represent a paradigm shift in sepsis diagnosis, emphasizing host response and organ dysfunction over systemic inflammation.
• Effective infection control necessitates a coordinated immune surveillance, effector, and resolution system, alongside immunological memory.

Purpose of the Study:

• To explore the novel concepts within the Sepsis-3 criteria.
• To examine the dysregulated immune responses in sepsis, including innate and adaptive immune system abnormalities.
• To identify gaps in understanding unifying organ failure mechanisms and immunomodulation strategies in sepsis.

Main Methods:

• Review and synthesis of current literature on Sepsis-3 criteria.
• Analysis of immune system alterations in sepsis, focusing on neutrophil, macrophage, T-cell, and B-cell function.
• Discussion of proposed mechanisms linking immune dysregulation to organ failure.

Main Results:

• Sepsis-3 criteria incorporate dysregulated host responses, remove SIRS criteria, utilize SOFA scores for organ dysfunction, and define septic shock as a sepsis subset.
• In sepsis, both innate (neutrophil, macrophage) and adaptive (lymphocyte, T/B cells) immune systems exhibit profound functional and numerical abnormalities.
• Epigenetic changes and altered lymphocyte populations in sepsis survivors may elevate risks of rehospitalization and mortality.

Conclusions:

• Significant gaps remain in understanding the unifying mechanisms of organ failure in sepsis.
• Further research into the immune response trajectory and modifiable mechanisms is essential for developing successful immunomodulation therapies.
• The current understanding highlights the complexity of sepsis pathophysiology and the need for advanced diagnostic and therapeutic approaches.