Basically, type III hypersensitivity is mediated by accumulation of immune complexes formation which may elicit inflammation. These reactions can be systemic or localized. Formation of immune complexes are originated from many infections and it is essential for antigen clearance. Their emergence can be stimulated by both endogenous and exogenous antigens. Example of endogenous antigens are bacteria and virus meanwhile exogenous antigens such as DNA can be seen in systemic lupus erythematosus (SLE). Under certain circumstances, immune complexes may escape from clearance phase leading to their deposition at tissue sites such as kidneys, joints, and blood vessels. The pathological potential of immune complexes can be determined by their size, solubility, net charge and ability to fix complement.
When immune complexes deposited in tissues, they may trigger inflammatory responses by activating the complement and release biologically active fragments such as anaphylotoxins C3a and C5a. Complement system is part of innate immune defense and mediates humoral and cellular interactions within immune response. It can be activated by classical pathway, alternative pathway and lectin pathway. Immune complexes in type III hypersensitivity activates the classical pathway. C1 binds to Fc region of immune complexes and their binding cleaves the C4- and C4b-bound C2 to generate the C3 convertase, C4b2b. C3 convertase then converts C3 to C3b and C3a. The C3b molecules act as opsonin in which they bind covalently to pathogen, mark it as target for pathogen destruction by phagocytes. C3b binds to C3 convertase to form C5 convertase which cleave C5 into C5a and C5b.
C3a and C5a plays important role in inflammation and activate immune cells and non-myeloid cells. These anaphylatoxins induce respiratory or oxidative burst in macrophages, eosinophils, and neutrophils. Also, C3a, C4a and C5a induce histamine production by basophils and mast cells which cause vasodilation. Increased vascular permeability increases the emigration of leukocytes which eventually cause tissue damage. Thus, symptom of hypersensitivity such as skin rashes appear. Furthermore, the complement proteins can act as chemoattractant for inflammatory cells such as neutrophils. The recruitment of neutrophils to the inflammation area functioned to destroy pathogens by phagocytosis or release bactericidal agents. Moreover, activated complement system may stimulate membrane attack complex by C5b, C6, C7, C8 and C9 proteins. This complex forms transmembrane channels and disrupt phospholipid bilayers of target cells, leading to cell lysis and death.
