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Type II Hypersensitivity

Type II Hypersensitivity

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Type II Hypersensitivity reactions occur 1-3 hours after antigen exposure.

Mediated by IgG antibodies and have cytotoxic and complement-activating effects. Recall that the complement cascade produces various proteins that promote inflammation, phagocytosis, and cell lysis.

Three mechanisms of antibody-mediated hypersensitivity:
Opsonization, inflammation, and, cellular dysfunction.

Opsonization

Mechanisms

Coats cells in antibodies, leads to phagocytosis and/or complement activation.

IgG binding of cell-bound antigens initiates the complement cascade, which generates active proteins.
Some of these proteins, including C3b, are deposited on the cell surface.

Thus, neutrophils can recognize the opsonized cell via two mechanisms:
The high-affinity Fc receptor can bind with the Fc region of the IgG antibody.
The C3b receptor can bind with the deposited complement on the cell's surface.

In both cases, binding promotes phagocytosis of the host cell.

Examples:

Transfusion reactions
Occur when host IgG antibodies bind donor cell antigens and C1 proteins, initiates complement cascade.
The complement cascade ultimately produces a Membrane Attack Complex (MAC); the MAC allows massive water influx into the cell, causing its lysis.

Hemolytic disease of the fetus and newborn
Maternal anti-Rh+ antibodies attack fetal Rh+ red blood cells.
The maternal antibodies were produced in response to prior pregnancy with a Rh+ fetus; upon subsequent exposure to a another Rh+ fetus, the maternal antibodies readily react.

Autoimmune blood cell destruction
Occurs when one's own blood cells are targeted:

  • Anemia can result when red blood cells are destroyed.
  • Agranulocytosis, when granulocytes, such as neutrophils, are targeted.
  • Thrombocytopenia, when platelets are removed.

Drug hapten
These reactions occur when haptens adhere directly to the cell surface.
IgG antibodies bind the hapten and activate complement system, phagocytosis occurs. Penicillin is an example of a drug that can cause type II hypersensitivity reactions.

IgG-induced inflammation

Inflammation occurs when antibodies are deposited in the tissues.

Neutrophil Fc receptor binding and complement activation leads to recruitment of additional leukocytes, including macrophages and additional neutrophils.

The released inflammatory products, including enzymes and reactive oxygen species, cause local tissue injury.
IgG antibodies specific to host tissues can cause severe destruction.

Examples

Vasculitis
Anti-neutrophil cytoplasmic antibodies (ANCAs) can induce vasculitis, which is inflammation of the blood vessels. This may show up as small reddish purple lesions in the skin, or larger bruise-like patterns of decay.

Treatments include methotrexate, prednisone, and cyclophosphamide, which suppress the immune response.

Goodpasture's syndrome
Caused by antibodies that attack the basement membranes of renal glomeruli and/or respiratory alveoli; specifically, the antibodies attack type IV collagen in the tissues.

In a histological sample of an affected glomerulus, we would see the characteristic crescent-shaped area formed by excessive fibrin and cellular material.

In a sample of lung tissue, we would see hemorrhaging in the inflamed alveoli.

Goodpasture's syndrome may be treated with corticosteroids and cyclophosphamide, or plasmapheresis, which removes the attacking antibodies.

Cellular Dysfunction
Antibodies bind cellular receptors and cause dysfunction; two classic examples are myasthenia gravis and Graves' disease.

In Myasthenia gravis, IgG binds the acetylcholine receptors on the muscle tissue; thus, acetylcholine released from the nerve cell cannot bind and stimulate muscle contraction.

For example, eyelid drooping, called ptosis, is common in individuals with myasthenia gravis. Drooping occurs because antibodies block or destroy the acetylcholine receptors, thus inhibiting eyelid muscle contraction.

Immuno-suppressive steroids may reduce circulating IgG antibodies to treat muscle weakness.

Graves Disease
Caused by binding of thyroid-stimulating antibody to the TSH receptor; as its name suggests, this has a stimulatory effect, and induces excessive thyroid hormone production.

Excessive thyroid hormone production in periorbital tissues can produce Graves' opthalmopathy, which is characterized by proptosis caused by swelling and adipose deposition.

Enlargement of the thyroid gland, called goiter, is caused by chronic thyroid stimulation. However, be aware that goiter can be indicative of hyper- or hypo-thyroidism; both states can involve overstimulation of the thyroid gland.

Hypothyroidism
TSH-stimulating blocking antibody can inhibit thyroid hormone production.

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Images:
Histology (Mark Braun, MD: http://medsci.indiana.edu/c602web/602/c602web/toc.htm)
Goiter - External Neck (Arkiv for Ringsaker, Hamar, Vang, Stange og Loten, Hedmarksmuseets fotoarkiv, HHB-00185)
Goiter - Thyroid (Ed Uthman)