Immunology and pathophysiology

Sarcoidosis is considered the archetype of immune granulomatous disorders, since immunoregulatory mechanisms that play a part in the development of the sarcoid granuloma may modulate pathogenetic events leading to granuloma development in other granulomatous diseases [1]. Remarkable advances have been made in understanding general immunological and molecular aspects of the mechanisms leading to granuloma formation and the development of fibrosis in sarcoidosis. In particular, the sarcoid granuloma is considered to be the consequence of a crippled immunological response against an unidentifed antigen that has persisted at sites of disease involvement, perhaps because of its low solubility and degradability. Indeed, although hypersensitivity reactions commonly resolve, the balance between events that mediate resolution or perpetuation of inflammatory responses may be altered in patients with chronic sarcoidosis. The persistence of the aetiological agents and/or an imbalance of mechanisms for the removal of inflammatory cells and their by-products ultimately lead to an ongoing inflammatory response. As a result, cytokines with pro-inflammatory destructive biological functions are locally produced; overall, these cytokines set the stage for the development of irreversible remodelling of lung tissue, progression toward pulmonary granuloma formation, and, in some individuals, irreversible development of pulmonary fibrosis. The aim of the present chapter is to provide an overview of the available knowledge concerning the mechanisms leading to the inflammatory processes that occur at common sites of involvement in sarcoidosis. A detailed description of the cellular interactions that govern the dynamics of granuloma formation is also included.