Immune complex

An immune complex, sometimes called an antigen-antibody complex or antigen-bound antibody, is a

The ratio of antigen to antibody determines size and shape of immune complex.[3] This, in turn, determines the effect of the immune complex. Many innate immune cells have FcRs, which are membrane-bound receptors that bind the constant regions of antibodies. Most FcRs on innate immune cells have low affinity for a singular antibody, and instead need to bind to an immune complex containing multiple antibodies in order to begin their intracellular signaling pathway and pass along a message from outside to inside of the cell.^[3] Additionally, the grouping and binding together of multiple immune complexes allows for an increase in the avidity, or strength of binding, of the FcRs. This allows innate immune cells to get multiple inputs at once and prevents them from being activated early.^[3]

Immune complexes may themselves cause illness when they are deposited in organs, for example, in certain forms of vasculitis. This is the third form of hypersensitivity in the Gell-Coombs classification, called type III hypersensitivity.^[4] Such hypersensitivity progressing to disease states produces the immune complex diseases.

Immune complex deposition is a prominent feature of several autoimmune diseases, including

Immune complexes, particularly those made of IgG, also play a variety of roles in the activation and regulation of phagocytes, which include dendritic cells (DCs) and macrophages. Immune complexes are better at inducing DC maturation than an antigen on its own.^[10] Again, the low affinity of many FcγR for IgG means that only immune complexes, not single antibodies, can induce the FcγR’s signaling cascade. When compared to single antibodies binding to FcγRs, immune complexes binding to FcγRs cause significant changes in internalization and processing of antigen, maturation of the vesicles containing the internalized antigen, and activation in DCs and macrophages.^[11] There are multiple classes of macrophages and DCs that express different FcγRs, which have differing affinities for single antibodies and immune complexes.^[11] This allows the response of the DC or macrophage to be tuned precisely, subsequently tuning the level of IgG. These diverse FcγRs cause different responses in their DCs or macrophages by initiating different signaling pathways that can either activate or inhibit cellular functions.^[11] The binding of the immune complex to the DC’s membrane-bound receptor and internalization of the immune complex and receptor begins the process of antigen presentation, which allows the DC to activate T cells. Via this process, immune complexes cause enhanced T cell activation.^[11]

Elimination of opsonized immune complexes

Type I FcγRs, another type of IgG constant region receptor, can bind to IgG immune complexes and lead to the elimination of the opsonized complex. Immune complexes bind to multiple type I FcγRs, which cluster on the cell surface and begin the ITAM signaling pathway. This signaling pathway involves the phosphorylation of specific amino acids within a sequence of proteins and eventually leads to elimination of opsonized immune complex.^[9]

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