What role does complement play in tissue damage caused by immune complexes?

In the context of connective tissue disease, the complement system plays a critical role in the tissue damage associated with Type III hypersensitivity, or immune-complex reactions.

When antigen-antibody complexes form in the circulation and are deposited in tissues—such as the blood vessels, kidneys, joints, or skin—they trigger the classical pathway of complement activation. This process leads to several injurious effects:12

• Inflammatory Response: The activation of complement releases small protein fragments that promote inflammation by increasing the permeability of blood vessels and causing mast cells to release histamine.32
• Cellular Recruitment: Complement activation attracts granulocytes and macrophages to the site of deposition.2
• Tissue Destruction: The recruited cells and the complement cascade itself release tissue-damaging substances, including enzymes that locally destroy tissue.2
• Vascular Damage: Complement activation contributes to platelet stickiness and vascular injury, which are characteristic features of conditions like systemic lupus erythematosus and rheumatoid arthritis.12