The long-time consequences of systemic inflammation and sepsis on t-cell immunity

Markwart, Robby

Systemic Inflammatory Response Syndromes (SIRS), including sepsis, describe a broad spectrum of immunological disorders with a very heterogeneous clinical manifestation. A SIRS caused by infectious triggers is defined as sepsis and with mortality rates exceeding 30% and totally 56000 deaths per annum, septic syndromes are the third most common causes of death after cardiovascular diseases and cancer in Germany. Acute episodes of SIRS and sepsis are characterised by an excessive and de-regulated inflammatory host response leading to organ and tissue damage and most fatally to death. The uncontrolled release of pro- and anti-inflammatory immune mediators is the root of immune suppressive states in patients at acute and post-acute stages of the disease. Malfunction of T-cells, a major component of adaptive immunity, has been shown to contribute to acute disease-induced immunosuppression but very little is known about the functional state of T-cells at post-acute and late stages of SIRS and sepsis. The present thesis provides an in-depth analysis of T-cell immunity at post-acute of SIRS and sepsis. Four different murine disease models were employed to account for the large clinical heterogeneity of the syndromes. The data presented here show that SIRS and sepsis lead to protracted systemic loss of T-cells but do not induce persistent cellular defects in adaptive T-cell function. T-cell activation and responses were intensively characterised by the examination of activation marker up-regulation, T-cell proliferation capacity and detailed T-cell receptor signalling studies. T-cell analyses were extended by the employment of secondary infection models allowing to investigate antigen-specific effector T-cell responses on multiple levels, including cytokine production and activation marker up-regulation. Ex vivo and in vivo effector T-cell studies in background of secondary infections confirm that SIRS and sepsis do not induce protracted inherent alterations in T-cell function.

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Markwart, Robby: The long-time consequences of systemic inflammation and sepsis on t-cell immunity. 2015.

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