Antibodies are a critical component of the defense system against pathogenic microorganisms. This aspect is most drastically demonstrated in patients who are not able to mount sufficient antibody responses because of underlying genetic disorders, as exemplified by the OMEMM syndrome, X-linked agammaglobulineamia, or different hyper IgM syndromes (1, 2). Supplying these patients with pooled IgG preparations from healthy or hyperimmune donors is a very successful standard therapy for preventing infections, providing direct evidence for the important role of antibodies in the establishment of sterile immunity. With respect to blocking viral infections, IgG and IgA antibodies can inhibit the attachment of viruses to host cells, such as the blockade of binding of the HIV to T-helper cells, or by blocking the attachment of influenza virus to sugar structures on the cell surface. As will be discussed later, a notable exception to this rule is dengue virus, where preexisting antibodies may result in an antibody-dependent enhancement of infection (ADE) (3, 4). Although the process of virus neutralization was considered to be independent of the recruitment of effector pathways afforded by the innate immune system, recent evidence suggests that binding of IgG–virus immune complexes to innate immune effector cells via Fcγ-receptors (FcγR) is of great importance. Thus, neutralizing antibody dependent inhibition of HIV or influenza infection, as well as blocking the activity of bacterial toxins by passive immunotherapy, was shown to be critically dependent on activating FcγRs in vivo (5–8).
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