First of all, the reaction between antibodies (IgG or
IgM) and soluble antigens in the serum resulted in the formation of circulating
antigens-antibody complex (Abbas & Lichtman, 2011). The soluble immune
complex are usually cleared and removed by the phagocytic cells. However, in
some cases, due to large amount of immune complex formed, the immune complex
cannot be easily removed by the phagocytic cell and may be deposited in vessel
walls or extravascular tissues (Rao, 2002). The deposition of immune complex
can lead to tissue damage mainly due to the antibody-mediated complement
activation and release of lytic enzymes from neutrophils (Lydyard, Whelan &
Fanger, 2011). This immune complex-mediated tissue damage is called as Type III
hypersensitivity or also known as Immune complex hypersensitivity.

            The antigen-antibody complex
activates the complement system via the classical pathway which will release the
complement byproducts that recruit leukocytes and induce inflammation. First,
the immune complex will activate the C1 which later will activate the C4 and C2
to produce C4b2b (C3 convertase).The C3 convertase then will convert C3 to C3a
and C3b. The C3b with C4b2b will form C4b2b3b (C5 convertase) which will then
convert C5 into C5a and C5b. The C5b with C6, C7, C8 and C9 will form C5-9
which also known as membrane attack complex (Todd & Spickett, 2010).

            The C3a and C5a acts as the
chemotactic factors that attract the neutrophils to the site of immune complex
deposition (Rao, 2002). Meanwhile, C3b act as opsonin that enhances
phagocytosis (Todd & Spickett, 2010). If the immune complexes bind to cell
such as red blood cells and platelets, the C3b will opsonised the cells. Then,
the cells may be ingested and destroyed by the phagocytes (neutrophils) as the
reactive oxygen species (ROS) and lysosomal enzyme released in the
phagolysosome (Abbas & Lichtman, 2011). However, if the immune complexes
attached to the basement membrane, the phagocytosis process will be interfered.
This causes the neutrophils to release lytic enzyme in the extracellular spaces
due to fail attempt of phagocytosis. The release of the lytic enzyme along with
the membrane attack complex of the complement will then damage the tissues
where the immune complex are deposited and also the adjacent tissues (Rao,
2002). Hence, it can be concluded that the Type III hypersensitivity related to
the tissue damage due to immune complex-mediated reaction.