16th January 2024

Pathophysiology

HP is a result of complex genetic predisposition and environmental factors. Differences in susceptibility to HP are related to polymorphisms of the major histocompatibility complex (MHC) class II molecules (mainly HLA-DR and DQ). These are responsible for presentation of processed exogenous antigens to T-lymphocytes, which initiate the antigen-specific immune response.

A combination of type III (immune complex-mediated) and type IV (delayed) hypersensitivity reactions are implicated in HP. Exposure to the causative agent triggers a type III reaction after initial sensitisation. Repetitive exposure leads to a delayed hypersensitivity (Type IV) reaction, triggering activation of CD8 cytotoxic T cells. This leads to macrophage activation and granuloma formation. Disease progression, such as in fibrotic HP, is linked to an exaggerated T-cell immune response, specifically the TH2 response, which is believed to promote collagen deposition and fibrosis of the lung.