The immune system defends the body, protecting against foreign invaders like bacteria and viruses. However, this protective response can become exaggerated or misdirected, leading to harmful effects on the body’s own tissues. These inappropriate immune reactions are known as hypersensitivity reactions, causing damage. There are several categories of these reactions, with Type III being one specific type that involves immune complexes.
Immune Complex Formation
Immune complexes are structures formed when antibodies, immune proteins, bind to specific foreign substances called antigens. This binding is a normal and beneficial part of the immune response, as it tags antigens for removal from the body. These complexes are efficiently cleared by scavenger cells like macrophages and by a group of blood proteins known as the complement system.
The complement system plays a role in this clearance process, facilitating the recognition and removal of immune complexes. Red blood cells can bind to complement-coated immune complexes and transport them to the liver and spleen, where they are then removed by phagocytes. This efficient removal mechanism ensures that these complexes do not accumulate and cause harm within the body.
The Development of Type III Hypersensitivity
Type III hypersensitivity reactions occur when immune complexes are not efficiently cleared, or are formed in large quantities. These complexes can then deposit in various tissues, including the walls of blood vessels, kidney glomeruli, and joint capsules. Once deposited, these immune complexes activate the classical pathway of the complement system.
The activation of complement leads to the production of inflammatory molecules, such as C3a and C5a, attracting other immune cells to the site of deposition. Among these attracted cells, neutrophils are notably prominent. When neutrophils arrive, they attempt to engulf the deposited immune complexes. Since the complexes are often bound to tissues, the neutrophils cannot fully engulf them and instead release their lysosomal enzymes and reactive oxygen species into the surrounding area. This uncontrolled release of inflammatory substances causes localized tissue damage and inflammation.
Associated Conditions and Triggers
Type III hypersensitivity contributes to the pathology of several conditions. One classic example is serum sickness, occurring after exposure to certain foreign proteins, like antivenoms or certain medications. In serum sickness, immune complexes deposit in tissues like joints and blood vessel linings, causing symptoms such as fever, rash, and joint pain.
Systemic lupus erythematosus (SLE) is another autoimmune disease where immune complex deposition is a key feature, affecting organs like the kidneys, skin, and joints. Rheumatoid arthritis also involves immune complexes, which deposit in the joints, leading to chronic inflammation and damage.
Certain kidney diseases, like post-streptococcal glomerulonephritis, develop after a streptococcal infection, where bacterial antigens and antibodies form complexes that settle in the kidneys, causing inflammation and kidney dysfunction. Hypersensitivity pneumonitis, often seen in conditions like “farmer’s lung,” arises from inhaling environmental antigens, leading to immune complex deposition and inflammation in the lungs. Triggers for these reactions can include specific drugs such as penicillin, various bacterial or viral infections, and inhaled environmental allergens.
Identification and Management
Identifying Type III hypersensitivity reactions involves recognizing a patient’s symptoms, which can vary widely depending on the affected tissues. Common presentations include skin rashes, joint pain, and signs of kidney problems like proteinuria. Diagnostic approaches involve a clinical assessment alongside laboratory tests.
Blood tests may include measuring complement levels, which are often decreased due to consumption during inflammation. Detecting circulating immune complexes or specific autoantibodies can also aid in diagnosis. A tissue biopsy of the affected organ may be performed to visualize immune complex deposits and inflammatory cell infiltration.
Management focuses on reducing inflammation and suppressing the immune response. Anti-inflammatory medications, such as corticosteroids, are used to alleviate symptoms and reduce tissue damage. In more severe or persistent cases, immunosuppressants may be prescribed. Key management involves identifying and avoiding the specific trigger or antigen if possible.