biologics are larger and are therefore noticed by the immune system. This results in a response that affects the biologics activity"
Answers
To date, it is known that the complicated sepsis syndrome may lead to both widespread activation and dysfunction of the innate immune system (Souza and others 2010). The innate immune system is to coordinate a defensive response, including both humoral and cellular components. Through recognition of invading microbes or microbial products, the innate immune system responds with a generalized response pattern, which is mediated in large part by the release of secretory proteins or cytokines (Oberholzer and others 2001; Efron and Moldawer 2003). However, activation of host innate immunity may occur not only after a microbial invasion, but also subsequent to exposure to internal “danger” signals produced by cell injury, tissue ischemia, hypoxia, and necrosis (Oberholzer and others 2001). As the innate immune system activates severely enough, the host response itself can drive the patient to manifest SIRS, or even shock and MODS/MOF. Although some patients survive the initial SIRS insult, these patients remain at an increased risk of developing secondary or opportunistic infections because of the frequent onset of a compensatory anti-inflammatory response syndrome (CARS). At the initial stage of sepsis, there is a release of large quantities of pro-inflammatory mediators, including TNF-α, IFN-γ, IL-33, and IL-2 (Hirsiger and others 2012), whereas, with the progression of disease condition, immunosuppression would be elicited, including macrophage deactivation, reduced antigen presentation, suppression of reproductive activity of lymphocytes, and the release of a number of anti-inflammatory cytokines, such as IL-10, IL-13, and IL-27. Further, a shift in the T-helper cell (Th) pattern to a Th2 cells, accompanied by apoptosis of a large number of lymphocytes, might lead to an increase in susceptibility to infection (Luan and others 2012). A growing body of evidence shows that innate immune cells (including Tregs, regulatory DCs, and invariant NKT [iNKT]) from patients with severe sepsis are able to promote an upsurge in anti-inflammatory cytokines and reverse the Th2 type response, rendering the patient to enter a state of immune depression and CARS. Therefore, both innate immunity and inflammation must be considered in the development of severe sepsis.