Sepsis syndromes: Understanding the role of innate and acquired immunity

An Intact innate and acquired immune response are essential for defeating s ystemic microbial infections. Recognition molecules, inflammatory cells, an d the cytokines they produce are the principal means for host tissues to re cognize Invading microbes and to initiate intercellular communication betwe en the innate and acquired immune systems. However, activation of host Inna te immunity may also occur in the absence of microbial recognition, through expression of internal "danger" signals produced by tissue ischemia and ne crosis. When activation of the innate immune system is severe enough, the h ost response itself can propel the patient into a systemic inflammatory res ponse syndrome (SIRS), or even multiple system organ failure (MSOF) and sho ck. Although most patients survive the initial SIRS insult, these patients remain at increased risk of developing secondary or opportunistic Infection s because of the frequent onset of a compensatory anti-inflammatory respons e syndrome (CARS). The Initial activation of the Innate Immune response oft en leads to macrophage deactivation, T-cell anergy, and the rapid apoptotic loss of lymphoid tissues, which all contribute to the development of this CARS syndrome and its associated morbidity and mortality. Initial efforts t o treat the septic patient with anticytokine therapies directed at the SIRS response have been disappointing, and therapeutic efforts to modify the im mune response during sepsis syndromes will require a more thorough understa nding of the innate and acquired Immune responses and the increased apoptos is in the lymphoid tissue.