Deposition of Immune Complexes. In the next phase, the circulating antigen-antibody complexes are deposited in various tissues. The factors that determine whether immune complex formation will lead to tissue deposition and disease are not fully understood, but the major influences seem to be the characteristics of the complexes and local vascular alterations. In general, complexes of medium size that are formed when antigen is in slight excess are the most pathogenic. Organs where blood is filtered at high
Fig. 5.15 Immunecomplexdisease.Thesequentialphasesintheinductionofsystemicimmunecomplex–mediateddiseases(typeIIIhypersensitivity).
http://ebooksmedicine.net pressure to form other fluids, like urine and synovial fluid, are sites where immune complexes become concentrated and deposit; hence, immune complex disease often affects glomeruli and joints.
Inflammation and Tissue Injury. Once deposited in tissues, immune complexes initiate an acute inflammatory reaction via complement activation and engagement of leukocyte Fc receptors. Typically, the antibodies are IgG or IgM. Deposition of complement proteins can be detected at the site of injury. Consumption of complement during the active phase of the disease decreases serum levels of C3, which can be used as a marker for disease activity. During this phase (approximately 10 days after antigen administration), clinical features such as fever, urticaria, joint pain (arthralgia), lymph node enlargement, and proteinuria appear. Wherever complexes deposit, the tissue damage is similar. The resultant inflammatory lesion is termed vasculitis if it occurs in blood vessels, glomerulonephritis if it occurs in renal glomeruli, arthritis if it occurs in the joints, and so on.
MORPHOLOGYTheprincipalmorphologicmanifestationofimmunecomplexinjuryisacute vasculitis, associatedwithfibrinoidnecrosisofthevesselwallandintenseneutrophilicinfiltration(Fig.3.12,Chapter3).Whendepositedinthekidney,thecomplexescanbeseenonimmunofluorescencemicroscopyasgranulardepositsofimmunoglobulinandcomplementandonelectronmicroscopyaselectron-densedepositsalongtheglomerularbasementmembrane(see
Fig.5.24
In acute serum sickness induced by administration of a single large dose of antigen, the lesions tend to resolve as a result of phagocytosis and degradation of the immune complexes. A form of chronic serum sickness results from repeated or prolonged exposure to an antigen. This occurs in several diseases, such as systemic lupus erythematosus (SLE), which is associated with persistent antibody responses to autoantigens. In many diseases, the morphologic changes and other findings suggest immune complex deposition, but the inciting antigens are unknown. Included in this category are membranous glomerulonephritis and several vasculitides.
A model of local immune complex diseases is the Arthus reaction, in which an area of tissue necrosis appears as a result of acute immune complex vasculitis. The reaction is produced experimentally by injecting an antigen into the skin of a previously immunized animal with preformed antibody. Immune complexes form as the antigen diffuses into the vascular wall at the site of injection, triggering the same inflammatory reaction and histologic appearance as in systemic immune complex disease. Arthus lesions evolve over a few hours and reach a peak 4 to 10 hours after injection, when the injection site develops edema and hemorrhage, occasionally followed by ulceration.
Antibodiescancoat(opsonize)cells,withorwithoutcomplementproteins,andtargetthesecellsforphagocytosisbyphagocytes(macrophages),whichexpressreceptorsfortheFctailsoflgGandforcomplementproteins.Theresultisdepletionoftheopsonizedcells.