The body’s immune system defends against various harmful invaders such as bacteria, viruses, and toxins. Antibodies, also known as immunoglobulins, are specialized proteins produced by this system to identify and neutralize these foreign substances. Among the different types of antibodies, Immunoglobulin G (IgG) is the most abundant, making up about 75-80% of all antibodies in human blood. IgG plays an important role in providing long-term protection, circulating widely throughout the body’s fluids and tissues to protect against threats.
The Structure of IgG
IgG antibodies possess a distinctive Y-shaped structure, which is important for their function. Each IgG molecule is composed of four polypeptide chains: two identical heavy chains and two identical light chains. These chains are held together by disulfide bonds. The heavy chains, also known as gamma (γ) chains, weigh approximately 50 kilodaltons each, while the light chains are about 25 kilodaltons.
Each heavy and light chain contains both variable and constant regions. The variable regions, at the tips of the “Y” arms, are diverse in their amino acid sequences, allowing IgG to bind specifically to many antigens. The constant regions, which make up the rest of the antibody, interact with other immune components. The hinge region connects the upper arms (Fab regions) to the lower stem (Fc region), allowing flexibility to bind multiple targets.
Humans have four subclasses of IgG: IgG1, IgG2, IgG3, and IgG4. While they share a similar overall Y-shaped structure, these subclasses exhibit subtle structural differences, particularly in their hinge regions. These variations influence how effectively each subclass interacts with the immune system. IgG1 is the most prevalent subclass, accounting for 60-65% of total IgG, followed by IgG2 (20-25%), IgG3 (5-10%), and IgG4 (less than 4%).
Diverse Functions of IgG
IgG antibodies perform several functions in the immune system. A primary function is neutralization, where IgG binds directly to pathogens or toxins, blocking their ability to interact with host cells. For example, IgG can prevent viruses from attaching to and entering cells, disarming them. It also renders bacterial toxins harmless.
IgG also acts as an opsonin, tagging pathogens for destruction. When IgG binds to antigens on pathogens, it marks them for engulfment and elimination by phagocytic cells like macrophages and neutrophils. The Fc region interacts with specialized Fc receptors on these phagocytes, facilitating their uptake and degradation. This enhances pathogen clearance.
Certain IgG subclasses can activate the classical complement pathway, a protein cascade that helps eliminate microbes and damaged cells. Upon binding to antigens, IgG can trigger this pathway, leading to the formation of a membrane attack complex that can lyse pathogens. The complement system also contributes to opsonization and the promotion of inflammation, aiding immune defense.
Another function of IgG is antibody-dependent cell-mediated cytotoxicity (ADCC). In this mechanism, IgG antibodies bind to antigens on infected or abnormal cells (e.g., virus-infected or tumor cells). The Fc region of the bound IgG then recruits and engages effector cells, such as natural killer (NK) cells. Once bound, the NK cells release cytotoxic substances like perforin and granzymes, inducing target cell destruction.
An important function of IgG is its ability to cross the placenta from mother to fetus. This transfer of maternal IgG provides the fetus and newborn with passive immunity, protecting them from infections before their own immune system is fully developed. This placental transfer is mediated by the FcRn receptor in the placenta. Transfer efficiency varies by IgG subclass, with IgG1 and IgG3 transferring more readily than IgG2 and IgG4.
IgG in Health and Disease
IgG plays a role in preventing and combating infections and long-term immunity. Following an initial exposure to a pathogen, the immune system mounts a primary response, producing antibodies, including IgG, to fight infection. Upon subsequent exposure, the immune system rapidly generates a stronger secondary immune response with higher levels of specific IgG, quickly neutralizing the threat. This immunological memory explains vaccine effectiveness.
While IgG defends the body, it can also contribute to disease. In autoimmune diseases, the immune system mistakenly produces IgG antibodies that attack healthy tissues. Examples include systemic lupus erythematosus (SLE) and vasculitis, where IgG can cause inflammation and tissue damage. Understanding these responses is important for developing autoimmune treatments.
IgG’s involvement in allergic reactions is less prominent than that of IgE, which is primarily associated with immediate hypersensitivity reactions (e.g., hay fever, asthma). However, IgG can be involved in less common allergic responses or desensitization therapies. For instance, in certain food allergies, IgG antibodies may be present, though their direct role in acute allergic symptoms is debated.
Beyond its natural roles, IgG is an important tool in medicine. It is used in diagnostic tests to detect past infections by identifying specific IgG antibodies, indicating previous exposure or vaccination. Measuring IgG levels also assesses overall immune status. Therapeutically, intravenous immunoglobulin (IVIG) therapy involves administering pooled IgG from healthy donors to patients with compromised immune systems or autoimmune conditions. IVIG provides replacement antibodies for primary immunodeficiencies or modulates the immune system in inflammatory and autoimmune disorders (e.g., Guillain-Barré syndrome, Kawasaki’s disease).