Immunoglobulin G (IgG) is the most abundant type of antibody in the human body, making up approximately 75% of all antibodies found in the bloodstream and other bodily fluids. IgG antibodies circulate throughout the body, identifying and neutralizing harmful substances like bacteria, viruses, and toxins. Produced by plasma B cells, they are especially important in the body’s secondary immune response, targeting previously encountered pathogens.
Diverse Mechanisms of IgG Action
IgG employs several distinct mechanisms to combat infections and protect the body.
Neutralization
One primary function of IgG is neutralization, where it directly binds to pathogens or toxins to prevent them from causing harm. For instance, IgG can attach to viral particles, blocking their ability to bind to and enter host cells, stopping infection from spreading. Similarly, IgG can bind to bacterial toxins, rendering them inactive and preventing them from damaging body tissues.
Opsonization
IgG also facilitates the removal of pathogens through a process called opsonization, often described as “tagging” for destruction. When IgG antibodies coat the surface of a pathogen, they make it more recognizable and appealing to phagocytic cells, such as macrophages and neutrophils. These immune cells have specialized receptors that bind to the Fc portion of the IgG molecule, enabling them to engulf and digest the tagged pathogen more efficiently. This mechanism significantly enhances the clearance rate of microbes from the bloodstream.
Complement Activation
Another defense mechanism initiated by IgG is the activation of the complement system. This system involves a cascade of proteins that, once triggered, can directly destroy pathogens or amplify other immune responses. When IgG antibodies bind to antigens on a pathogen’s surface, they can form clusters recognized by C1, the first component of the classical complement pathway. This binding activates C1, initiating a series of enzymatic reactions leading to the formation of a membrane attack complex (MAC) that creates pores in the pathogen’s membrane, causing it to lyse and die.
Antibody-Dependent Cell-mediated Cytotoxicity (ADCC)
IgG also plays a role in Antibody-Dependent Cell-mediated Cytotoxicity (ADCC). In ADCC, IgG antibodies bind to antigens on the surface of infected or abnormal cells, such as virus-infected cells or cancer cells. Once bound, the Fc portion of the IgG molecule is recognized by specific receptors, particularly FcγRIII (CD16), found on immune effector cells like Natural Killer (NK) cells. Upon this binding, the NK cell releases cytotoxic substances, such as perforin and granzymes, which induce the target cell to undergo programmed cell death.
Unique Contributions to Immunity
IgG stands out among other antibody types due to its distinctive and long-lasting roles in immunity, providing sustained protection and early life defense.
Long-Term Immunological Memory
IgG is a primary contributor to long-term immunological memory, which is the immune system’s ability to “remember” previously encountered pathogens. After an initial infection or vaccination, plasma B cells produce IgG antibodies that persist in the bloodstream for extended periods, sometimes years or even decades. This persistence allows for a faster and more robust immune response upon subsequent exposure to the same pathogen, often preventing the development of disease symptoms. This rapid recall response is the fundamental principle behind how vaccines provide lasting protection.
Maternal Passive Immunity (Placental Transfer and Breast Milk)
IgG is the only antibody class capable of crossing the human placenta from mother to fetus. This transfer, mediated by specialized neonatal Fc receptors (FcRn) on placental cells, provides the newborn with passive immunity during the first months of life when their own immune system is still developing. This maternal IgG offers protection against a range of infections the mother has encountered. Additionally, IgG, along with IgA and IgM, is present in colostrum and breast milk, providing continued immune support to the infant’s gut and respiratory tract.
IgG in Health and Medical Contexts
The widespread presence and specific functions of IgG make it a valuable tool in various health and medical applications.
Diagnostic Tool
Measuring IgG levels in blood tests serves as a valuable diagnostic tool, providing insights into a person’s immune history and status. Elevated IgG levels can indicate a past exposure to an infection, confirming immunity to diseases like measles or chickenpox. These tests can also help diagnose chronic infections or certain autoimmune conditions.
Therapeutic Applications
Purified IgG antibodies are administered in a therapeutic approach known as Intravenous Immunoglobulin (IVIG) therapy. This treatment is used for patients with certain immune deficiencies, where their bodies do not produce enough functional IgG, to boost their immune system. IVIG is also employed to modulate an overactive immune response in individuals with autoimmune diseases, where the immune system mistakenly attacks the body’s own tissues. The mechanisms of IVIG involve blocking activating Fc receptors on immune cells and neutralizing pathogenic autoantibodies.
Role in Disease
Dysregulation of IgG can contribute to various health conditions. In autoimmune diseases, IgG antibodies can mistakenly target the body’s own cells and tissues, leading to inflammation and damage. Examples include rheumatoid arthritis and lupus, where autoantibodies contribute to disease progression. Conversely, in primary immunodeficiencies, the body may not produce enough functional IgG, making individuals more susceptible to recurrent infections. Low IgG levels can also be a symptom of certain acquired conditions.