Wednesday, September 7, 2011

Antibody dependent cell mediated cytotoxicity


Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) is a mechanism of cell-mediated immunity whereby an effector cell of the immune system actively lyses a target cell that has been bound by specific antibodies. It is one of the mechanisms through which antibodies, as part of the humoral immune response, can act to limit and contain infection. Classical ADCC is mediated by natural killer (NK) cellsneutrophils and eosinophils can also mediate ADCC. For example, eosinophils can kill certain parasitic worms known as helminths through ADCC. ADCC is part of the adaptive immune response due to its dependence on a prior antibody response.

ADCC by NK cells

The typical ADCC involves activation of NK cells by antibodies. An NK cell's Fc receptor recognizes the Fc portion of an antibody, such as IgG, which has bound to the surface of a pathogen-infected target cell. The most common Fc receptor on the surface of an NK Cell is called CD16 or FcγRIII. Once the Fc receptor binds to the Fc region of IgG, the Natural Killer cell releases cytokines such asIFN-γ, and cytotoxic granules containing perforin and granzymes that enter the target cell and promote cell death by triggering apoptosis. This is similar to, but independent of, responses by cytotoxic T cells (CTLs).

ADCC by eosinophils

Large parasites like helminths are too big to be engulfed and killed by phagocytosis. They also have an external structure or integument that is resistant to attack by substances released by neutrophilsand macrophages. However, an antibody called IgE can coat these parasites. The Fc receptor (FceRI) of an eosinophil can then recognize IgE. The interaction between FceRI and the Fc portion of helminth-bound IgE causes the eosinophil to degranulate.

Antibody-dependent cellular cytotoxicity

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