Formation and Deposition of Immune Complexes
The pathology begins when an antigen meets an antibody. They can bind directly in the bloodstream or extravascularly (in situ), forming circulating immune complexes (CICs).
Two types of antigens serve as sources of the problem:
- Exogenous: foreign proteins, viruses, or bacteria.
- Endogenous: the body's own tissues, against which autoantibodies are mistakenly produced.
The pathological effect of CICs manifests when they deposit in tissues. The walls of blood vessels and filtering systems (such as the renal glomeruli) are most frequently targeted. Depending on the affected areas, diseases are classified as generalized (affecting multiple organs) or local (affecting specific structures—joints, kidneys, or skin).
Mechanisms of Tissue Injury
The deposition of immune complexes beneath the vascular endothelium triggers a potent inflammatory cascade. The complement system acts as the primary driver of destruction:
- The C3b fraction acts as an opsonin, stimulating phagocytosis.
- Factor C5 attracts monocytes and band neutrophils to the site (chemotaxis).
- Anaphylatoxins (C3a, C5a) induce smooth muscle contraction and increase vascular permeability.
- The C5b-9 complex (membrane attack complex) directly disrupts cell membranes, causing cytolysis.
Recruited neutrophils bind to CICs via Fc receptors. Attempting to clear the complexes, leukocytes release lysosomal enzymes, prostaglandins, and reactive oxygen species, which literally digest surrounding tissues. Concurrently, Hageman factor is activated and platelet aggregation is triggered. As a result, microthrombosis occurs, the vascular lumen becomes occluded, and ischemia develops.
Systemic Immune Complex Diseases
A classic example of a generalized reaction is acute serum sickness, which occurs following repeated administration of large doses of foreign serum. Its pathogenesis includes three phases: formation of CICs in the blood, their deposition in tissues, and subsequent inflammation.
The severity of the process depends on the state of the mononuclear phagocyte system and the size of the complexes. Large CICs (when antibodies are in excess) are rapidly cleared by macrophages and cause virtually no damage. In contrast, small and medium complexes are highly pathogenic: they circulate in the blood for a long time and easily become trapped in tissues.
The clinical presentation (fever, urticaria, arthralgia, proteinuria, and lymphadenopathy) unfolds approximately 10 days after antigen exposure. Morphologically, this manifests as acute necrotizing vasculitis, arthritis, and glomerulonephritis (characterized by swelling and proliferation of endothelial and mesangial cells in renal glomeruli, accompanied by monocyte and neutrophil infiltration). If the antigen remains constantly present in the blood (antigenemia), the disease transitions into a chronic form.
The antigen is known in certain systemic conditions (e.g., autoantigen persistence in systemic lupus erythematosus). However, in rheumatoid arthritis, polyarteritis nodosa, and membranous nephropathy, the antigen often remains unidentified.
Local Reaction: The Arthus Phenomenon
When immune complexes form and act locally, a localized reaction occurs—the Arthus phenomenon. This is an acute immune complex vasculitis leading to localized tissue necrosis.
The reaction develops rapidly, with peak injury observed within 4 to 10 hours after antigen injection or contact. Macroscopically, this appears as an area of pronounced edema with areas of hemorrhage. Light microscopy clearly demonstrates fibrinoid necrosis of the vessel wall. The ultimate outcome of such injury is either vascular rupture with local hemorrhage or thrombosis (more common), leading to tissue ischemia.