Immunoglobulin G (IgG) is the most abundant class of Ig in nature, contributing 75%–80% of total immunoglobulins. It has two antigen-binding sites. After a secondary immunization, B lymphocytes secrete predominantly IgG molecules. IgG, unlike other immunoglobulins, can cross the placenta barrier and impart immunity to the foetus and also can penetrate into extravascular areas. IgG molecules are able to react with Fcγ receptors present on the surface of macrophages and some other cells. The interaction with Fc receptors initiates various effector reactions and particularly facilitates the destruction of potentially harmful germs recognized by IgG antibodies. IgG molecules can also activate complement by the classical pathway. 

IgG molecules play a central role in the humoral immune response providing protection from pathogens and their toxic products. They do so through their ability to recognize and bind to an immeasurable number of antigens via their variable domains and through their ability to interact with effector molecules and effector cells via their constant domains. Protection by IgG is mediated through three distinct mechanisms. Firstly, IgG neutralizes pathogens such as viruses and bacteria by binding to key pathogen surface proteins and preventing interaction of the pathogen with host cells. In doing so, the antibody neutralizes the ability of the pathogen to enter host cells and replicate. IgG similarly binds to toxins and blocks their ability to enter cells. A second means of confirming protection is through opsonization of pathogens that replicate outside of cells. In this instance, IgG binds to and coats the surface of the pathogen and through interaction with IgG–Fc receptors (FcγR) of phagocytic cells (e.g., macrophages and neutrophils) mediates ingestion by the phagocytic cell and pathogen destruction. The third mode of protection is through activation of the complement system. In the classical pathway of complement activation, pathogens bound by IgG are recognized by the C1q protein, triggering the complement cascade and resulting in pathogen phagocytosis and lysis.

IgG deficit may be due to a congenital primary disturbance (immunodeficiency congenital and acquired) and is a special risk in children. Polyclonal hyperimmunoglobulinemia is the normal response to infections, especially in hepatitis and cirrhosis as well as autoimmune diseases. Increases of monoclonal IgG are found in multiple myeloma, lymphocytic leukaemia, and Waldenström’s macroglobulinemia.