Fc receptor

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Fc receptor is a receptor on hemopoietic cells such as macrophages, neutrophils and mast cells. They will bind to the constant end of immunoglobulin after the antibodies have bound to antigens. The Fc receptors therefore increase the affinity phagocytic cells have for microbes. This causes phagocytosis and subsequent killing of the pathogen.

There are seven different types of Fc receptors. All of those are stimulating Fc receptors, except for the inhibiting Fcγ RII-B1 and B2. These two receptors contain immunoreceptor tyrosine based inhibition motifs (ITIMs) in their cytoplasmic tail, which activate inhibitory cellular responses.

Receptor	Fcγ RI (CD64)	Fcγ RII-A (CD32)	Fcγ RII-B2 (CD32)	Fcγ RII-B1 (CD32)	Fcγ RIII (CD16)	Fcε RI	Fcα RI
Relative binding	IgG1 ~200	IgG1 ~4	IgG1 ~4	IgG1 ~4	IgG1 ~1	IgE ~20,000	IgA1, IgA2 ~20
Cell type	Macrophages Neutrophils Eosinophils Dendritic cells	Macrophages Neutrophils Eosinophils Platelets Langerhans cells	Macrophages Neutophils Eosinophils	B Cells Mast cells	NK cells Eosinophils Macrophages Neutrophils Mast cells FDCs	Mast cells Eosinophils Basophils FDCs	Macrophages Neutrophils Eosinophils
Effect of ligation	Uptake Stimulation Activation of repiratory burst Induction of killing	Uptake Granule release (eosinophils)	Uptake Inhibition of stimulation	No uptake Inhibition of stimulation	Induction of killing (NK cells)	Secretion of granules	Uptake Induction of killing

[edit] Other actions

When IgG molecules, specific for a certain antigen or surface component, bind to the pathogen with their Fab region (fragment binding region), their Fc regions are pointed outwards, in direct reach of phagocytes. Phagocytes can now bind those Fc regions with their Fc receptors. On contact, a lot of loose bindings are formed, but together this is a tight system. This low individual affinity prevents Fcs from binding Fc receptors in the absence of antigen. This also prevents clotting of IgG on phagocytes when there is no antigen.

After the pathogen has been bound, interactions between Fc and Fc receptors result in engulfment of the pathogen. This engulfment is an active process of binding and releasing of the Fc:Fc receptor complex, in which the cell membrane of the phagocyte gradually encloses the pathogen.

Fcε RI has a different function. As indicated in the table above, its relative binding is much greater than the other ones. Fcε RI is the Fc receptor on granulocytes, essential for acting in allergic reactions and parasitic infections. In normal situations, in absence of an allergic antigen or parasite, these receptors are loaded with immonoglobulin IgE. In case of an antigen or parasite, it has to at least cross link two IgE molecules and their subsequent receptors on the surface of a mast cell. If the antigen succeeds in doing that, the mast cell is triggered to release its granules filled with inflammatory mediators. This method of releasing is pretty fast, since the granules were prepackaged and ready for release.

Pathogens that can not be ingested by phagocytes, like parasites such as Schistosoma mansoni, are covered with IgE and activated eosinophils will bind them with their Fcε RI and will literally pour its granules onto the parasite.

NK cells also have Fc receptors. These cells play an important role in innate immunity, so it is in some paradoxical that they bear Fc receptors, since those are structures that need immunoglobulins: proteins produced during adaptive immunity. And since they are part of innate immunity they need preformed antibody. This is only available in a secondary respons, in which one encounters the same pathogen/antigen again.