Type III hypersensitivity, in the Gell and Coombs classification of allergic reactions, occurs when there is accumulation of immune complexes ( antigen- antibody complexes) that have not been adequately cleared by innate immune cells, giving rise to an inflammatory response and attraction of

leukocyte White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...

s. There are three steps that lead to this response. The first step is immune complex formation, which involves the binding of antigens to antibodies to form mobile immune complexes. The second step is immune complex deposition, during which the complexes leave the plasma and are deposited into tissues. Finally, the third step is the inflammatory reaction, during which the

classical pathway Classical may refer to: European antiquity *Classical antiquity, a period of history from roughly the 7th or 8th century B.C.E. to the 5th century C.E. centered on the Mediterranean Sea *Classical architecture, architecture derived from Greek and ...

is activated and macrophages and neutrophils are recruited to the affected tissues. Such reactions may progress to immune complex diseases.

Types

Some clinical examples: Other examples are: *

Subacute bacterial endocarditis Subacute bacterial endocarditis, abbreviated SBE, is a type of endocarditis (more specifically, infective endocarditis). Subacute bacterial endocarditis can be considered a form of type III hypersensitivity. Signs and symptoms Among the signs of ...

*Symptoms of malaria

Signs and symptoms

Type III hypersensitivity occurs when there is an excess of antigen, leading to small immune complexes being formed that fix complement and are not cleared from the circulation. It involves soluble antigens that are not bound to cell surfaces (as opposed to those in type II hypersensitivity). When these antigens bind antibodies, immune complexes of different sizes form. Large complexes can be cleared by

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...

s but macrophages have difficulty in the disposal of small immune complexes. These immune complexes insert themselves into small blood vessels, joints, and glomeruli, causing symptoms. Unlike the free variant, a small immune complex bound to sites of deposition (like blood vessel walls) are far more capable of interacting with complement; these medium-sized complexes, formed in the slight excess of antigen, are viewed as being highly pathogenic. Such depositions in tissues often induce an inflammatory response, and can cause damage wherever they precipitate. The cause of damage is as a result of the action of cleaved complement

anaphylotoxin Anaphylatoxins, or complement peptides, are fragments ( C3a, C4a and C5a) that are produced as part of the activation of the complement system. Complement components C3, C4 and C5 are large glycoproteins that have important functions in the immun ...

s C3a and C5a, which, respectively, mediate the induction of granule release from mast cells (from which histamine can cause urticaria), and recruitment of inflammatory cells into the tissue (mainly those with lysosomal action, leading to tissue damage through frustrated phagocytosis by PMNs and macrophages). The reaction can take hours, days, or even weeks to develop, depending on whether or not there is immunological memory of the precipitating antigen. Typically, clinical features emerge a week following initial antigen challenge, when the deposited immune complexes can precipitate an inflammatory response. Because of the nature of the antibody aggregation, tissues that are associated with blood filtration at considerable osmotic and hydrostatic gradient (e.g. sites of urinary and synovial fluid formation, kidney glomeruli and joint tissues respectively) bear the brunt of the damage. Hence, vasculitis, glomerulonephritis and

arthritis Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In som ...

are commonly associated conditions as a result of type III hypersensitivity responses. As observed under methods of

histopathology Histopathology (compound of three Greek words: ''histos'' "tissue", πάθος ''pathos'' "suffering", and -λογία '' -logia'' "study of") refers to the microscopic examination of tissue in order to study the manifestations of disease. Spe ...

, acute

necrotizing vasculitis Necrotizing vasculitis, also called systemic necrotizing vasculitus, is a category of vasculitis, comprising vasculitides that present with necrosis. Examples include giant cell arteritis, microscopic polyangiitis, and granulomatosis with poly ...

within the affected tissues is observed concomitant to neutrophilic

infiltration Infiltration may refer to: Science, medicine, and engineering *Infiltration (hydrology), downward movement of water into soil *Infiltration (HVAC), a heating, ventilation, and air conditioning term for air leakage into buildings *Infiltration (me ...

, along with notable eosinophilic deposition ( fibrinoid necrosis). Often,

immunofluorescence Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on microbiological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specif ...

microscopy can be used to visualize the immune complexes. Skin response to hypersensitivity of this type is referred to as an

Arthus reaction In immunology, the Arthus reaction () is a type of local type III hypersensitivity reaction. Type III hypersensitivity reactions are immune complex-mediated, and involve the deposition of antigen/antibody complexes mainly in the vascular walls, s ...

and is characterized by local erythema and some induration. Platelet aggregation, especially in microvasculature, can cause localized clot formation, leading to blotchy hemorrhages. This typifies the response to injection of foreign antigen sufficient to lead to the condition of serum sickness. The relevance of the Gell and Coombs classification of allergic reactions is questioned in the modern-day understanding of allergy, and it has limited utility in clinical practice.

References

External links

{{Hypersensitivity and autoimmune diseases Hypersensitivity

Types

Signs and symptoms

See also

References

External links