For the first time, scientists have documented an organ-specific innate immune system. In research published in the April 18 edition of the journal Immunity, scientists at the University of California, San Diego (UCSD) School of Medicine outline the unique mechanism by which the lung shapes its defensive strategies against microbial invasion.
"This innate immune response is specific to the lung, and was probably designed to minimize collateral damage to lung tissue caused by unchecked inflammation," said Eyal Raz, M.D., Professor of Medicine at UCSD School of Medicine.
The body's respiratory tract is constantly exposed to inhaled particles or microorganisms. The alveola tiny air sacs in the lung where exchanges of gases between the respiratory and circulatory systems takes place are protected from invading microbes by the alveolar macrophage.
Macrophages are white blood cells involved in the inflammatory response throughout the body, cells normally on the alert for invaders to kill. Alveolar macrophages are unique among macrophages in the body, because their activation is inhibited by TGFb, a compound expressed in the lung by epithelial cells.
"Because the microenvironment of the alveola is a delicate one, it would be damaged if the macrophage immune system was in a constant battle-ready status," said Raz. "This could readily lead to the type of inflammation we see in autoimmune diseases of the lung such as asthma."
Therefore, the alveola possess a complex immune system in which the macrophage is repressed in its steady state, activated when called upon to fight invading microorganisms, and then re-repressed, in a circuit that is unique to this microenvironment.
"Dissecting this immune mechanism provides us with the knowledge of how we might prolong the activation status of alveolar macrophages. This knowledge could prove to be essential in combating any novel microbial agents that could infect the lower airways, such as a new flu strain or bioterrorist agents," said Raz.