Immune complexes are structures formed when antibodies encounter and bind to foreign substances, known as antigens. This binding creates a larger, clustered structure that tags the invader for disposal. The formation of these complexes is a necessary part of a healthy immune response, allowing the body to neutralize and efficiently clear pathogens from circulation.
The primary function of these structures is to facilitate clearance, as their size makes them easier for specialized cells like phagocytes to recognize and engulf. If clearance fails, however, these complexes accumulate and deposit in various tissues. When this process is overwhelmed, the complexes trigger damaging inflammation, moving from a beneficial role to a source of disease.
How Immune Complexes Are Formed
Immune complex formation relies on the direct chemical interaction between an antibody and its specific antigen. Antibodies, typically IgG or IgM, recognize and attach to antigens in the blood or other body fluids. This binding forms a lattice structure, where multiple antibodies bridge several antigen molecules together, creating the complex.
The ratio between antigen and antibody determines the complex’s fate. Complexes formed at the zone of equivalence, where concentrations are balanced, tend to be the largest and most insoluble. These large, insoluble complexes are difficult to clear from the bloodstream and are the most likely to cause pathology.
Smaller complexes formed in states of high antibody or high antigen excess are generally more soluble and cleared more easily. The complement system, a cascade of plasma proteins, is instrumental in normal clearance by binding to and solubilizing the complexes. This complement coating allows specialized receptors on red blood cells to transport the complexes to the liver and spleen, where macrophages dismantle them.
When Immune Complexes Cause Disease
Disease arises when circulating immune complexes are not efficiently removed and become trapped in the small blood vessels of various organs. This deposition triggers an intense, localized inflammatory reaction known as Type III Hypersensitivity. The trapped complexes activate the complement cascade, which releases chemical signals that attract and activate inflammatory cells like neutrophils.
The accumulation of neutrophils at the deposition site leads to the release of destructive enzymes and reactive oxygen species. This localized damage is an unintentional consequence of the immune system’s attempt to eliminate the trapped complex. The clinical manifestation depends entirely on the tissue where the deposition occurs.
Common sites for deposition include the kidney, where complexes can become lodged in the glomeruli, causing glomerulonephritis. This can severely impair the kidney’s filtering function, a condition often seen in systemic lupus erythematosus (SLE) and post-streptococcal infections. Deposition in the synovium of joints can lead to arthritis, while lodging in the walls of small blood vessels causes vasculitis, characterized by inflammation and damage to the vessel wall. Serum sickness, a classic example of systemic immune complex disease, presents with fever, joint pain, and rash due to widespread complex deposition.
Identifying Immune Complexes in the Body
The detection of immune complexes or the evidence of their activity is an important step in diagnosing systemic inflammatory conditions. A direct approach involves laboratory assays designed to measure circulating immune complexes (CIC) in blood serum. Tests like the C1q binding assay rely on the complexes’ ability to bind components of the complement system.
Another diagnostic tool is the measurement of specific complement proteins, particularly C3 and C4, in the serum. When immune complexes activate the classical complement pathway, they consume these proteins in large quantities. Depressed levels of C3 and C4 in the blood often indicate ongoing, systemic immune complex consumption.
For diagnosis and to identify the exact location of damage, clinicians may use tissue biopsy followed by immunofluorescence microscopy. A sample of the affected organ is stained with fluorescent antibodies that bind to human antibodies and complement proteins. Under the microscope, immune complex deposition appears as a characteristic granular pattern along the filtration membranes, visually confirming the pathological process.