Antigen-Induced Immunomodulation in the Pathogenesis of Atherosclerosis

Figure 1

Inflammatory basis of atherosclerotic plaque formation. Led by inflammatory signals derived from the damaged endothelium, monocytes and lymphocytes migrate into the vessel wall. Monocytes differentiate into macrophages that recognise and phagocytiose oxidised LDL particles. The protein component of the LDL particle is processed and presented in the form of peptides by macrophages (also by dendritic cells) to T-lymphocytes in the context of the major histocompatibility complex class II (MHC-II). Other self or foreign antigens that may gain access to the vascular wall can also trigger similar mechanisms. It is believed that most of these lymphocytes differentiate in situ, under the influence of the specific antigen stimulation, into effector T-cells, but this has yet to be demonstrated. Upon activation, both macrophages and lymphocytes release a range of proinflammatory molecules including chemokines which stimulate the migration of smooth muscle cells (SMCs) from the media. SMCs contribute to foam cell and fibrous cap formation. This process is facilitated by cytokines such as IFN𝛾 and TNFα secreted by proatherogenic Th1 cells and also IL-12 secreted by macrophages and foam cells. Eventually foam cells die by apoptosis in situ leaving nondegradable cholesterol crystals that form the lipid core of the plaque.