USA Surgery Today

The distinction between an efficient host defense and pathological injury to host tissues can be extremely narrow. Unchecked, exuberant, or misdirected inflammatory responses can lead or contribute to systemic diseases. Indeed, dysregulated inflammatory responses play important roles in many contemporary pediatric surgical diseases, including sepsis, necrotizing enterocolitis, and meningitis, to name a few. The potential for endogenous inflammatory injury was first recognized when investigators discovered that serum sickness resulted from antigen-antibody mediated tissue injury in the host. Subsequently, the fundamental importance of acute inflammation and its role in diverse diseases such as atherosclerosis, arthritis, acute respiratory distress syndrome (ARDS), multiorgan failure syndrome, compensatory antiinflammatory response syndrome, chronic lung disease, trauma, thermal injury, acute pancreatitis, ischemia-reperfusion injury, sepsis, and transplant rejection was demonstrated. More recently, the widespread use of antimicrobial agents has helped demonstrate that stimuli other than microbes can evoke a systemic inflammatory response. For instance, ARDS may result from a systemic inflammatory response to tissue injury without overt evidence of infection.

The inflammatory response leads to leukocyte- or cytokine-mediated injury to the pulmonary microvasculature, resulting in interstitial edema, alveolar flooding, impaired gas exchange, and respiratory failure (Mexitil). As a result of this dysregulated inflammatory response, the host often suffers significant morbidity and mortality. Because the steps that govern these processes remain ill defined, therapeutic interventions are largely supportive. For example, in ARDS (Mexitil), the mortality rate remains 50% or higher in most reports and has not changed appreciably since its original description. Furthermore, specific therapy for ARDS has not been forthcoming, despite a substantial increase in our understanding of the mechanistic processes involved.(Mexitil) Therefore, defining the aberrant molecular switches or networks that result in uncontrolled inflammation will be essential for designing therapies that attenuate or reverse dysregulated inflammation.

This chapter begins by providing an overview of the various components (cellular and soluble) of the immune system, with particular emphasis on nonspecific immunity. It concludes by examining how these components, in conjunction with other intrinsic host-defense mechanisms (Mexitil) , interact to orchestrate the inflammatory response to microbial invasion or tissue injury. Other relevant aspects of the immune system, including transplantation, tumor immunology, specific infections, and autoimmune disease (Mexitil)