Type III hypersensitivity

Antibodies binding to equivalent amounts of soluble antigens give rise to immune complex formation. The antigens involved in inducing the pathogenic immune response can be either foreign or self, and the antibodies either IgG or IgM. When complexes are formed, they usually activate complement and then bind to C3b receptors on erythrocytes. The erythrocytes are then responsible for removing complexes from the plasma and transporting them to the sinusoids of the liver and spleen, where they are removed by macrophages. However, if immune complexes are formed in great excess of antigen, or if the complex is very small and soluble, the reticuloendothelial system will not be able to degrade them efficiently. These complexes will circulate in the blood and subsequently deposit in various tissues of the body, inducing local inflammation. The resulting pathogenic features depend on the sites of immune complex deposition.

Factors that influence immune complex deposition

1. Size: larger immune complexes fix complement more efficiently and are removed more quickly than those of medium size.

2. Isotype: IgA complexes do not bind efficiently to erythrocytes, thus they tend to deposit to a greater extent.

3. Defective phagocytosis and/or complement binding systems which allow immune complexes to bind to the endothelial wall.

4. Biochemical properties of the antigen and antibody: altered glycosylation of IgG has been found in rheumatoid arthritis and this may hamper phagocytosis.

5. Hemodynamic factors: the plasma goes through the capillary walls of the glomeruli and synovia at high hydrostatic pressure, thus facilitating immune complex deposition at these sites.

Immune complexes mediate the inflammatory reaction through several mechanisms:

1. Activation of complement components, with production of C3a and C5a fragments (anaphylatoxins) which bind to complement receptors on:

(a) basophils and mast cells, causing the release of preformed and newly formed mediators, such as histamine, PGD,, PAF, leukotrienes and cytokines. This results in the series of events already described for mast cell degranulation following cross-linking by antigen of mast cell-bound IgF., i.e. increase in vascular permeability, which facilitates the deposition of immune complexes in the blood vessel wall and further production of complement, recruitment of inflammatory cells and smooth muscle contraction;

(b) polymorphonuclear leukocytes, causing increase in their adherence to the vessel walls, in their ability to ingest particles and in their attraction to the affected areas.

2. Binding to Fc receptors on basophils and platelets, triggering, on the one hand, the release of vasoactive amines, which leads to increase in vascular permeability and hemorrhage, and, on the other, platelet aggregation and microthrombosis.

3. Stimulating macrophages to produce proinflammatory cytokines.

Diseases caused by immune complexes generally follows:

1. Persistent bacterial or viral (low-grade) infections: streptococcus, leprosy, syphilis, viral hepatitis. Acute post-streptococcal glomerulonephritis is due to immune complex deposition on the basement membrane of the glomeruli. In lepromatous leprosy and secondary syphilis, the mycobacterium and the treponema antigens, respectively, can cause deposition of complexes in the joints, skin and kidney, with consequent local damage.

2. Persistent exposure to and inhalation of environmental antigens, i.e. moulds and animal danders. Examples are the extrinsic alveolitis found in farmers' lung and pigeon fanciers' lung. The antibody involved is IgG, not IgF.

3. Persistent autoantibody formation in autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). SLE is characterized by autoantibodies against nuclear constituents, such as DNA and nucleoprotein antigens. Large numbers of immune complexes are produced, tending to deposit in the small vessel walls of the glomeruli, joints and brain and causing injury. In RA, IgG

Table 1 Continued




mRNA size (kb)/tissue


Protein size


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  • Abraham
    Why immune complex bind basement membrane hypersensitivity 3?
    2 years ago
  • LENA
    How is rhemtoid arthritis related to type 3 hypersensitivity?
    3 months ago

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