The second type of hypersensitivity reaction, known as a cytotoxic reaction, uses the mechanism of IgG and IgM antibodies directed against antigens on the cell surface or extracellular matrix, and the antigen can be internal or external. Antibody binding to antigens leads to cell lysis through complement activation or antibody-dependent cell-mediated cytotoxicity (ADCC, leading to inflammation and tissue damage (Gülsen et al., 2020). An example is hemolytic anemia, in which antibodies bind to red blood cell antigens, which leads to their destruction by the complement system.
The third type of hypersensitivity reaction, mediated by the immune complex, has a slightly different mechanism. It involves immune complexes (antigen-antibody complexes) formed in circulation and subsequently deposited in various tissues. Deposited complexes activate the complement system, which recruits neutrophils and other inflammatory cells (Jutel et al., 2023). An example is systemic lupus erythematosus, in which immune complexes are deposited in the kidneys, joints, and other tissues, causing inflammation and organ damage.
Differences are observed in three main parameters. First, the location of antigens in the second type, where they are associated with cells, makes the immune response highly specific to cells, while in the third type, the antigens are soluble. They form complexes that can circulate and be deposited in various tissues, causing widespread damage. The participation of antibodies also distinguishes the second type: IgG or IgM, which bind directly to antigens on cell surfaces, leading to direct damage (McCance & Huether, 2019). In the third, complex formation with soluble antigens precipitates, causing tissue damage. Finally, a key difference lies in the effector mechanisms: the second type activates complement and ADCC, which cause direct lysis and phagocytosis, and the third carries out similar activation through the deposition of immune complexes, thereby promoting the recruitment of neutrophils that secrete enzymes that cause tissue damage.
References
Gülsen, A., Wedi, B., & Jappe, U. (2020). Hypersensitivity reactions to biologics (part II): classifications and current diagnostic and treatment approaches. Allergo Journal International, 29, 139-154.
Jutel, M., Agache, I., Zemelka‐Wiacek, M., Akdis, M., Chivato, T., Del Giacco, S. & Akdis, C. A. (2023). Nomenclature of allergic diseases and hypersensitivity reactions: Adapted to modern needs: An EAACI position paper. Allergy, 78(11), 2851-2874.
McCance, K. L., & Huether, S. E. (2019). Pathophysiology: The biologic basis for disease in adults and children. Mosby.