Immune complex formation is a normal process that removes foreign antigens from the circulation. Removal of immune complexes by phagocytes bearing Fc or complement receptors prevents their deposition at other sites. The efficiency of uptake of immune complexes by either Fc receptors or CR1 is proportional to the number of IgG molecules associated with the complex.
Type III Autoimmune Reactions
(Immune Complex Disease)
Autoantibodies also cause disease by forming network of autoantibodies bound to their antigens (immune complexes). The antigen-antibody complexes can deposit in tissue, causing inflammatory lesions. Studies of serum sickness led to the first description of an immune complex disease. Serum sickeness is manifested by fever, glomerulonephritis, vasculitis, urticaria and arthritis, appearing seven to twenty-one days after primary immunization with a foreign protein. Two consequences of immune complex formation are complement fixation and binding to Fc or complement receptors on phagocytes. Clearance is facilitated by the binding of immune complexes to C3b receptors (CR1) on erythrocytes, which retain the complexes in the circulation until their removal by the reticuloendothelial cells of the spleen or liver.
Type IIB Hypersensitivity: Myasthenia Gravis
Myasthenia gravis is an autoimmune disease caused by inhibitory (antagonistic) autoantibodies that bind and block the acetylcholine receptor (AChR), causing muscular weakness and fatigue. The AChR is found at postsinaptic membranes of neuromuscular junctions and binds acetylcholine released from a nerve ending, transiently opening a calcium channel. The signal is terminated by acetylcholine esterase, an enzyme located in the basal lamina between the nerve ending and the postsynaptic membrane. As in mothers with Graves disease, transplacental passage of IgG autoantibodies from mothers with myasthenia gravis can cause transient neonatal myasthenia gravis. Anti-AChR autoantibodies cause disease by down-regulating expression of the receptor and by complement-mediated lysis of the cells bearing the AChR. Intermolecular cross-linking of AChR by the autoantibodies may lead to antigenic modulation.
Type IIB Hypersensitivity: Graves Disease
Graves disease is an organ-specific autoimmune disease of the thyroid mediated by stimulatory (agonistic) autoantibodies. Autoantibodies to the thyroid stimulating hormone receptor (TSHR) cause hyperthroidism in patients with Graves disease. The pathogenicity of anti-TSHR autoantibodies is demonstrated by the occurence of neonatal Graves disease after passive transplacental transfer of IgG thyroid stimulating autoantibodies in Graves disease inhibit binding of TSH to its receptor by binding to a conformational epitope (the part of the antigen recognized by an antibody) of the extracellular domain of the TSHR. Although the autoantibodies appear to interact with TSHR somewhat differently than the natural ligand, they nevertheles stimulate TSHR signaling, causing increased production of thyroid hormone.
CASE I. AUTOIMMUNE HEMOLYTIC ANEMIA (AIHA)
A. TYPE II AUTOIMMUNE REACTION
COMMENT:
AIHA can occur in a variety of circumstances, including neoplastic diseases (most often lymphomas), connective tissue diseases (such as SLE), and infections (viral, bacterial, or mycoplasma). Or it may be drug induced (classically penicillin). The initial treatment is to diagnose and treat the underlying cause or remove offending agents. If this is not possible, corticosteroid such as prednisone are often used. If patients do not respond, then consideration is given to the use of cytotoxic drugs (eg azathioprine or vincristine) or splenectomy.
CASE I. AUTOIMMUNE HEMOLYTIC ANEMIA (AIHA)
A. TYPE II AUTOIMMUNE REACTION
COMMENT:
AIHA in patients with SLE is usually due to the presence of warm reactive autoantibodies against the Rh antigen. As the autoantibody-coated erythrocytes pass through the spleen, phagocytes bearing Fc receptors remove some of the immunoglobulin on the cell surface along with some of the cell membrane, which subsequently reseals, causing the erythrocyte to take the form of spherocyte. Eventually, the erythrocyte is unable to be repaired and is removed from the circulation. If this occurs faster than new erythrocytes can be produced (normal life span of an erythrocyte is about 120 days) then anemia develops. The elevated indirect bilirubin (a measure of bilirubin before the liver has a chance to process it) is a result of the increased breakdown of hemoglobin.
CASE I. AUTOIMMUNE HEMOLYTIC ANEMIA (AIHA)
A. TYPE II AUTOIMMUNE REACTION
On the basis of these clinical findings, the diagnoses of AIHA and thrombocytopenia were made. She was treated with prednisone. Initially her platelet count improved to 120,000. However, after three months of treatment, her anemia did not improve. She gained twenty pounds and noted easy bruising, fatigue and difficulty sleeping as well as “feeling on edge all the time”. since she had not improved and was experiencing side effects of prednisone, she was given a penumococcal pneumonia vaccination before surgery to remove her spleen. After splenectomy, her anemia, thrombocytopenia, and some of her fatigue resolved. After tapering the prednisone dose, she felt “felt normal”. Two years later, her symptoms recurred and laboratory tests confirmed evidence of active hemolytic anemia. A liver-spleen scan indicated the presence of an accessory spleen (present in 10-30% of normal population), which was removed. She is currently symptom free.
