How does granulomatosis affect the immune system?

Granulomatosis, particularly in the context of granulomatosis with polyangiitis (GPA), previously known as Wegener's granulomatosis, has several effects on the immune system:

Abnormal Immune Response: In GPA, there is an overactivation and dysregulation of the immune system, leading to the production of autoantibodies, specifically antineutrophil cytoplasmic antibodies (ANCA), particularly c-ANCA directed against proteinase 3 (PR3). These autoantibodies target and damage small blood vessels, especially in the lungs and kidneys, causing inflammation and tissue destruction.

ANCA-mediated Vasculitis: The interaction of ANCA with their target antigens, such as PR3, activates neutrophils and induces inflammation within the blood vessel walls. This leads to vasculitis, characterized by the destruction and inflammation of small blood vessels, resulting in tissue damage in various organs.

Immune Complex Deposition: ANCA and immune complexes containing ANCA and PR3 can deposit in the affected tissues, particularly the kidneys and lungs. This deposition activates the complement system, a part of the immune response that normally helps clear infections, but in this case, it contributes to tissue damage and inflammation.

Granuloma Formation: Granulomas are collections of immune cells, including macrophages and lymphocytes, that form in response to foreign substances or chronic inflammation. In granulomatosis, granulomas can develop in various organs, such as the lungs, kidneys, and upper respiratory tract. These granulomas may cause tissue destruction and contribute to the symptoms of the disease.

Impaired Wound Healing: The excessive inflammation and tissue damage caused by granulomatosis can impair normal wound healing processes. This can lead to complications such as chronic ulcers, infections, and delayed healing of surgical wounds.

Overall, granulomatosis affects the immune system by causing dysregulated immune responses, ANCA-mediated vasculitis, immune complex deposition, granuloma formation, and impaired wound healing, resulting in damage to various organs and tissues. Understanding these immunological mechanisms is essential for developing effective treatments and managing the disease.