In type III hypersensitivity reaction, antigen-antibody complex deposited on host cells induces complement fixation and enhance inflammatory reaction. It is mainly mediated by Ig-G antibodies complement protein and neutrophils.
The reaction of antibodies with the soluble antigens, generates immune complexes. Generally, these reactions facilitate the clearance of antigens by phagocytes But some times the presence of large number of immune complexes can lead to tissue damage and initiate type III hypersensitivity reactions. For this reason, type III hypersensitivity is also known as immune complex mediated hypersensitivity. The soluble antigen involved in these reactions, may be exogenous (produced by the pathogen during the infection) or endogenous (self-antigens such as proteins, glycoproteins etc).
Types: Type III hypersensitivity is mainly two types: A. Localized type III hypersensitivity, in which the immune complex damage a limited area from where they are first deposited. B. Systemic type III hypersensitivity, in which multiple sites are damaged in the body and this reaction is a part of complex autoimmune disease.
Mentioned disorders: The deposition of immune complex in the tissues can give rise to symptoms such as fever, joint pain, lymph node enlargement, vasculitis (if inflammation occurs in the blood vessels), glomerulonephritis (if occurs in kidney), serum sickness etc.
Mediators of Type III hypersensitivity: The main mediator of this hypersensitivity-reaction is Ig-G antibodies but there are also some other co-operators such as mast cells, neutrophils, macrophages and some complement proteins.
Mechanism of reaction: The antibody mainly Ig-G binds to the soluble antigen and form a circulating immune complex, which is a normal part of our adaptive immune response. After that the immune complex binds to the mast cells or macrophages and is recognized by the phagocytes followed by Fc receptor mediated recognition, which engulf and destroy them by complement activation. It triggers the formation of membrane attack complex (MAC) and ultimately results in the lysis of the cells containing immune complex.
But the problem occurs when the immune complexes become more larger or present in a huge number. The binding of the immune complexes to the mast cell or macrophages or neutrophils triggers the release of vasoactive mediator or inflammatory cytokines. These mediators start to interact with the capillary epithelium and increase its permeability. In this condition, the immune complexes may be deposited in the blood vessels or tissues and initiate local inflammatory reaction. Complement fixation results the production of anaphylatoxin chemokines which attract more neutrophils and macrophages. This reaction facilitates the secretion of proinflammatory chemokines and cytokines and also protease. Proteases digest the basement membrane proteins (such as collagen, elastin etc), located bellow the epithelial layer of the vessel wall. The tissue damage is further mediated by some oxygen free radicals released from the activated neutrophils. Through this process type III hypersensitivity occurs.