Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
Antibodies consist of four polypeptide chains: two identical heavy chains of approximately 440 amino acids each, and two identical light chains composed of roughly 220 amino acids each. These chains are arranged in a Y-shaped structure that is held together by a combination of covalent disulfide bonds and noncovalent bonds. Furthermore, most antibodies carry sugar residues. The process of adding sugar side chains to a protein is called glycosylation.
Both the light chain and heavy chain contribute to the antigen binding site at each of the tips of the Y structure. These 110-130 amino acids are highly variable to allow recognition of an almost unlimited number of antigens. This region is also called the variable region and is part of the antigen binding fragment.
Each arm of the Y-shaped unit carries an identical antigen binding site. Antibodies can crosslink antigens: when one arm binds to one antigen and the other arm binds to a second, structurally identical antigen. Crosslinking is facilitated by the flexible hinge region that connects the antibody’s arms to the stem and allows variable distances between antigen binding sites. Large lattices of crosslinked antigens are subsequently engulfed more quickly and easily by macrophages, removing larger amounts of the antigen at once.
The stem region of the antibody is also called the fragment crystallizable (Fc) region and determines the effector function of the antibody. Via the Fc domain, the antibody can interact with Fc receptors on other immune cells, such as B cells, macrophages, and mast cells. The Fc region is often glycosylated, hindering or allowing Fc receptor access. Altering the glycosylation state of the antibody, therefore, allows rapid modulation of antibody function.
Antibodies are classified by their number of Y-shaped structures and type of heavy chains. Antibodies of the class IgD, IgE and IgG have a single Y-shaped structure, providing two identical antigen binding sites at the tips of their arms. In more scientific terms: they have a valency of two. IgD, IgE, and IgG differ, however, in the composition of disulfide and noncovalent bonds between their two heavy chains. IgA can occur as a monomer or as a dimer, resembling two Ys that are joined at their base. As a dimer, IgA has four identical antigen binding sites—a valency of four. IgM can occur as a monomer but is more often encountered as a pentamer, giving it a valency of 10.
IgG antibodies are the most abundant antibody molecules in blood and are secreted in large volumes when a specific pathogen is encountered for the second time. IgGs contribute to pathogen elimination in several ways. They opsonize pathogens to trigger phagocytosis by macrophages or neutrophils. The activity of these phagocytic cells is enhanced by the complement system, a cascade of enzymatic proteins. The complement system is itself triggered by IgG. Furthermore, IgGs are the only antibodies that can cross the placenta from the mother to the fetus. They are also secreted into the mother’s milk, thereby offering passive immunity that protects the infant from infections.
IgA protects mucosal surfaces such as the gastrointestinal, respiratory, and urogenital tracts. It foremost neutralizes bacteria, preventing their movement across epithelia. IgA is also secreted into mucus, tears, saliva, and colostrum (the antibody-rich secretion of a mother’s breast for the first days after giving birth). IgA occurs as a dimer when it is secreted and as a monomer in body fluids.
Monomers of the IgM class are the first to appear on naive B cells. IgMs are the major class of antibodies that are secreted by B cells in response to the first exposure to an antigen—the primary antibody response. When an antigen binds to an IgM molecule, it activates the complement system and neutralizes pathogens.
The functions of IgD antibodies are not well understood but seem to resemble those of IgM.
IgE is challenging to study due to their low levels in body fluids and are mostly known for their negative impact on human well-being: allergies. During an allergic reaction, IgE binds to its cognate antigen. Subsequently, the Fc region of IgE binds to mast cells and basophils, a type of white blood cell. The interaction of IgE and the Fc-receptor on the cell surface elicits the release of histamines and interleukins, which in turn causes allergic symptoms such as sneezing and itching.
Antibodies are an important tool in many research disciplines as well as in the diagnosis, and sometimes treatment of disease. To produce antibodies, an antigen is injected into a farm or laboratory animal, often rabbits, chickens, hamsters, or goats, and is later isolated from the animal’s blood.
