Fc receptors: Cell activators of antibody functions

Abstract

At the onset of an infection early defense systems, such as complement, get into action. Specialized leukocytes (white blood cells) of the innate immune sys tem, including monocytes, macrophages, and neutro phils also participate as a first line of defense against infections. These early responses are rapid but not very specific and are usually not enough to clear completely many infections. The adaptive immune system is also needed to finish the job against many microorganisms. Antibody molecules, produced during the adaptive immune response, are crucial for preventing recurrent infections. Although, IgG antibodies are essential for controlling infections, these molecules do not directly damage the microorganisms they recognize. Today, it is established that leukocytes of the innate immune system are responsible for the protective effects of these antibodies. IgG molecules bind to their cognate antigens and are in turn recognized by specific receptors (Fc γ receptors) on the membrane of leukocytes. Crosslinking these receptors on the surface of leukocytes leads to activation of several effector cell functions. These effector functions are geared toward the destruction of microbial pathogens and the induction of an inflammatory state that is beneficial during infections. However, in autoimmune diseases, antibodies can direct these effector functions against normal tissues and cause severe tissue damage. In recent years, several factors that can modulate the IgG-Fc γ R interaction have been elucidated. In this review, we describe the main types of Fc γ receptors, and our current view of how antibody variants interact with these receptors to initiate different cell responses. In addition, new findings on the signaling role of individual Fc γ receptors are also discussed.