type 111 Gell and Combs

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Type III Immune Complex Hypersensitivity

A. Reactions occur when soluble antigen and corresponding antibody unite and

activate complement. The Ag-Ab complexes form in blood and tissue spaces and

are deposited in the walls of blood vessels, in basement membranes, and in joint

synovia.

B. Arthus reaction demonstrated by Maurice Arthus in 1903.

1. Artificially induced in laboratory.

2. Induced localized inflammatory skin reaction in previously sensitized rabbit

(to horse serum) by intradermal injection of cognate Antigen.

Inflammation grossly visible after several hours

a. Longer time than Type I, but shorter than Type IV. Classified as immediate

because responsible antibodies can be passively transferred via serum.

b. Ag-Ab complexes form and adhere to vascular endothelium; complement system

activated and some of its chemotactic intermediates attract neutrophils to site.

Anaphylatoxins degranulate mast cells with resultant release of histamine that

causes constriction of arterioles and retards blood supply to area. Platelets

stimulated by the immune complex initiate the coagulation cascade, resulting in

fibrin deposits. Eventually vessels become clogged with thrombin and

accumulated cells, causing an exudate into the surrounding tissue (edema).

Deprivation of blood supply to area results in ischemic necrosis.

c. Only precipitating (multivalent) antibodies can elicit the Arthus reaction

(mainly IgG). Relatively large amounts of antigen required.

d. Reverse passive Arthus possible (Ab from sensitized animal injected

intradermally, Ag IV or at site).

C. Human lung hypersensitivities (Immune complex pneumonitis, allergic

pneumonitis, hypersensitivity pneumonitis)

1. Natural counterpoint of artificially induced Arthus reaction

2. Farmers lung, pigeon breeder's lung, mushroom workers lung etc.

3. Inhalation of allergen (fungal spores, animal danders, excretory products

etc.) sensitizes. Further exposure elicits IgE and IgG

D. Serum Sickness

Occurs in patients receiving large doses of foreign serums (horse

antitoxin against tetanus, antilymphocyte serum for immunosuppression of tissue

transplant, serum therapy for pneumococcal infection pre-antibiotics). 7-10

days following initial exposure to foreign serum patient develops malaise,

fever, nausea, vomiting, edema, lymphadenopathy, muscle and joint pains and

hives. Massive dose of antigen serves as challenging dose to stimulate Ab

production and as reactive dose. More chronic and less lethal than IgE mediated

anaphylaxis.

In general, findings of cryoglobulinemia (abnormal globulin that

precipitates at 4 degrees C and redissolves on warming) and/or decreased

complement levels suggest presence of immune complexes.