The high catalytic activity of IgM compared to IgG is not explained by the effects of avidity, since the multivalent binding of IgM prevents the low substrate concentrations used in the reaction. inflammatory, autoimmune diseases == 1. Introduction == Immunoglobulins (Igs) are involved in numerous molecular mechanisms of both innate and Vandetanib HCl adaptive immune systems due to the presence of two functional centers (antigen binding sites (Fab) and fragment crystallizable region (Fc)), as well as a combination of their unique Vandetanib HCl structural and functional properties. Generally, Igs combine the Fab domain-mediated antigen recognition process with the activation of various innate responses mediated by the involvement of various receptors, protective proteins and immune cells by the Fc domain [1]. For a long time, it was believed that the hosts immune system generates only highly specific antibodies (Abs) against pathogens [2]. However, the development of experimental methods and animal models made it possible to determine the extreme heterogeneity of the Igs pool, reflecting a wide variety of biological functions of Abs. Igs have been shown to exhibit their effector functions both in normal and pathological conditions, especially in inflammatory and autoimmune diseases (AIDs). The pathological role of Abs is well documented in the literature (e.g., [3]). At the same time, natural Igs are powerful immunomodulators that both induce and suppress immune responses and inflammatory processes [4]. However, much less attention is paid to the study of Ab effector functions beyond the classical concepts of immunology. Evidence of a significant functional diversity of Abs is the various identified therapeutic effects of intravenous Igs (IVIg) [5]. IVIg preparations are widely used to treat various immunological pathologies. A better understanding of these Ab functions can enrich existing therapeutic strategies. In this review, we circumstantially describe recent findings concerning the canonical and non-canonical functions of Igs. We discuss the broad diversity of naturally occurring Abs that explain the wide variety of Ab functions. In CHUK addition, we pay special attention to catalytic Abs, because they are associated with autoimmune and inflammatory disease states. For the first time, we systematically Vandetanib HCl summarize the diversity of catalytic Abs in normal and pathological conditions. Translational perspectives of knowledge about natural Abs for IVIg therapy are also considered. == 2. Canonical and Non-Canonical Functions of Immunoglobulins == The human Ab repertoire is created by somatic evolution in B cell populations, which allows the immune system to recognize and eradicate almost any antigen [6]. State-of-the-art immune repertoire next-generation sequencing technologies have allowed a deeper understanding of the diversity of Abs and B cell receptors and thus the immune status of the individuals [7,8,9]. The Ab repertoire is flexible and changeable throughout life. Flexibility is achieved due to the presence of an extensive repertoire of native Abs, the diversity of which is increased by somatic hypermutation after exposure to the antigen. Each of the approximately estimated 5 109B cells produces a specific B cell receptor or Ab through somatic recombination of variable (V), diversity (D), joining (J) and constant (C) gene segments (V(D)J recombination) [8,9]. The V(D)J recombination process results in a light (L) chain, assembled from V, J and C gene segments from one of the light chain loci, and a heavy (H) chain, assembled from V, D, J and C gene segments from the heavy chain locus [8]. Pairs of H and L chains combine to form the following Ab isotypes: monomeric IgG, IgE and IgD; dimeric IgA; and pentameric IgM. Fab contains the variable segments of H and L chains (VH and VL) that bind to a specific surface on the antigen (epitope). Each of the VH and VL segments contains three complementarity-determining regions (CDRs) and four framework regions. The CDRs contain the amino acid residues responsible for antigen binding (paratope). The process of somatic hypermutation after exposure to antigens introduces mutations, primarily in CDRs [8]. Moreover, Abs have constant domains involved in the formation of Fc, which is responsible for interacting with diverse Vandetanib HCl receptors or complement. Thus, a broad Abs repertoire, a unique structure and processes of affinity maturation determine the variety of practical activities of Abs. Ab-mediated biological functions should be considered according to practical level [10]. The simplest functional level indicates the elementary connection of the Fab website with the antigen to.