Chapter 12 - Inhibitory Receptors and Autoimmunity in the Mouse

Abstract

The immune system recognizes and eliminates invading microorganisms. It has evolved a number of complex mechanisms to achieve this goal, which center on an ability to distinguish between self and non-self and to limit autoreactivity. Critical to its function is the capacity to rapidly mount a potentially lethal response to pathogens but yet to limit and terminate the relevant pathways when they are no longer required. Thus, the immune system has evolved activatory mechanisms that facilitate a rapid response that are counterbalanced by inhibitory pathways. Loss of inhibitory signaling pathways is associated with both autoreactivity and excessive inflammatory responses, emphasizing their critical role. The innate and adaptive immune systems utilize a range of inhibitory receptors that control the strength and duration of an immune response. They facilitate the development of a measured response and play an important role in preventing autoreactivity. An increasing number of immune inhibitory receptors are identified in mice and humans. The generation of mice deficient in both inhibitory receptors and molecules downstream in inhibitory pathways has provided compelling evidence that inhibitory mechanism is critical for the prevention of autoimmunity. A better understanding of these pathways also allows the development of therapeutic agents that might modify inhibition and prevent or reduce autoimmune diseases.