Immunoglobulins, or antibodies, are proteins produced by the immune system to identify and neutralize foreign invaders like bacteria and viruses. Immunoglobulin G (IgG) is the most abundant type found in human blood serum, making up a significant portion of plasma proteins. IgG is categorized into four distinct subclasses, each with specialized roles in the body’s defense. These subclasses contribute to a strong immune response against various threats.
Understanding the Four IgG Subtypes
IgG is divided into four subclasses: IgG1, IgG2, IgG3, and IgG4. While highly conserved, they differ structurally, particularly in their hinge regions and upper CH2 domains, which are segments of the antibody’s constant region. These structural variations influence how each subclass interacts with other immune components.
IgG1
IgG1 is the most prevalent subclass, accounting for about 65% of total IgG in human serum. It is predominantly generated in response to protein antigens, such as those found on viruses or bacterial toxins. Its structure allows it to efficiently engage with various immune pathways.
IgG2
IgG2 accounts for about 25% of total IgG and responds to bacterial capsular polysaccharide antigens. These antigens are sugar-based molecules found on the surface of certain bacteria. IgG2 has a more rigid hinge region compared to IgG1, which influences its functional capabilities.
IgG3
IgG3 makes up about 6% of total IgG and has a unique structure. It features a significantly longer and more flexible hinge region than the other subclasses, containing up to 62 amino acids. This extended hinge provides greater flexibility, allowing it to bind to multiple targets simultaneously.
IgG4
IgG4 is the least abundant subclass, accounting for about 4% of total IgG. It is often observed during chronic antigen exposure, such as long-term immunotherapy or certain parasitic infections. IgG4 has a unique ability to undergo “Fab arm exchange,” where it swaps half-molecules with other IgG4 antibodies, creating hybrid antibodies.
How IgG Subtypes Defend the Body
Each IgG subclass has distinct characteristics regarding immune complex formation and effector cell triggering. Their unique structures dictate how effectively they neutralize threats and activate downstream immune processes. These functional differences allow the immune system to tailor its response to different types of pathogens.
IgG1
IgG1 is effective at activating the complement system, a cascade of proteins that helps clear pathogens and damaged cells. It also binds strongly to Fc receptors (FcγRs) found on various immune cells, such as macrophages and natural killer cells. This binding initiates effector functions like antibody-dependent cellular cytotoxicity (ADCC), targeting infected cells for destruction.
IgG2
IgG2 weakly activates the complement system. It also exhibits a lower affinity for some FcγRs compared to IgG1 and IgG3. This reduced binding capacity means it is less effective at triggering certain cellular effector functions, focusing its role more on direct neutralization.
IgG3
IgG3 is a strong activator of the complement system and binds strongly to Fc receptors. Its extended hinge region contributes to its enhanced ability to form large immune complexes and engage effector cells. IgG3 antibodies are often associated with robust effector responses to foreign antigens and parasitic infections, and can be among the first antibodies to appear during viral infections.
IgG4
IgG4 does not activate the complement system. It has a low affinity for activating FcγRs but a higher affinity for the inhibitory FcγRIIb. This characteristic suggests a role in modulating or preventing excessive immune responses, reducing inflammation and tissue damage during chronic antigen exposure.
IgG Subtypes and Their Role in Health and Disease
The distinct properties of IgG subclasses mean that imbalances or specific responses involving these antibodies can significantly impact health. Understanding their roles helps in diagnosing and managing various conditions, from protecting against infections to contributing to allergic reactions and autoimmune diseases.
Deficiencies
Deficiencies in specific IgG subclasses can lead to increased susceptibility to certain infections. For example, an IgG2 deficiency can predispose individuals to recurrent infections caused by encapsulated bacteria like Streptococcus pneumoniae.
Allergic and Immune-Mediated Conditions
IgG subtypes are also implicated in allergic responses and other immune-mediated conditions. IgG1 plays a major role in anaphylactic and allergic reactions, often with IgE antibodies. Elevated IgG4 levels are a recognized marker for IgG4-related diseases, a group of chronic inflammatory conditions that can affect various organs.
Placental Transfer
The ability of IgG antibodies to cross the placenta is another significant aspect of their role in health. IgG1 is the principal IgG subclass actively transported across the placenta from mother to fetus, providing passive immunity to newborns during their first few months of life.
Therapeutic Applications
In therapeutic applications, the unique characteristics of IgG subclasses are harnessed for treatments like immunotherapy. Monoclonal antibodies are often engineered to be of specific IgG subclasses to achieve desired effects, such as enhancing tumor cell killing or modulating immune responses in autoimmune diseases.