Explain the structure and functions of IgG immunoglobulin.

Structure of IgG Immunoglobulin

IgG is a Y-shaped molecule composed of four polypeptide chains: two identical heavy chains (approximately 50 kDa each) and two identical light chains (approximately 25 kDa each). These chains are linked together by disulfide bonds.

Heavy Chains

The heavy chains determine the immunoglobulin class (in this case, IgG). There are four subclasses of IgG in humans: IgG1, IgG2, IgG3, and IgG4, each with slightly different structural and functional properties. Each heavy chain consists of four immunoglobulin domains: one variable domain (VH) and three constant domains (CH1, CH2, and CH3). The variable domain is responsible for antigen binding, while the constant domains mediate effector functions.

Light Chains

There are two types of light chains: kappa (κ) and lambda (λ). Each light chain consists of two immunoglobulin domains: one variable domain (VL) and one constant domain (CL). Like the heavy chain variable domain, the light chain variable domain contributes to antigen binding specificity.

Fab and Fc Regions

The antigen-binding portion of the IgG molecule is formed by the variable regions of both the heavy and light chains, collectively known as the Fab (Fragment antigen-binding) region. The remaining portion of the molecule, the Fc (Fragment crystallizable) region, is formed by the constant regions of the heavy chains. The Fc region mediates interactions with immune cells and complement proteins, triggering effector functions.

Functions of IgG Immunoglobulin

1. Neutralization

IgG can neutralize pathogens and toxins by binding to them and preventing them from interacting with host cells. This is particularly important in preventing viral entry into cells. For example, IgG antibodies against SARS-CoV-2 neutralize the virus, preventing it from infecting cells.

2. Opsonization

IgG enhances phagocytosis by coating pathogens, a process called opsonization. The Fc region of IgG binds to Fc receptors on phagocytic cells (e.g., macrophages, neutrophils), promoting the engulfment and destruction of the pathogen. This significantly increases the efficiency of phagocytosis.

3. Complement Activation

IgG can activate the classical pathway of the complement system when it binds to antigens. This leads to the formation of the membrane attack complex (MAC), which lyses pathogens, and the release of inflammatory mediators that enhance the immune response. IgG1 and IgG3 are particularly effective at activating complement.

4. Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC)

IgG can mediate ADCC, where natural killer (NK) cells recognize and kill target cells coated with IgG antibodies. The Fc region of IgG binds to Fc receptors on NK cells, triggering the release of cytotoxic granules that kill the target cell. This is important in eliminating virus-infected cells and tumor cells.

5. Placental Transfer and Neonatal Immunity

IgG is the only immunoglobulin that can cross the placenta, providing passive immunity to the fetus. This protects the newborn from infections during the first few months of life, before their own immune system is fully developed. The FcRn receptor (neonatal Fc receptor) facilitates this transfer.

6. IgG Subclass Specific Functions

IgG Subclass	Complement Activation	Placental Transfer	Fc Receptor Binding
IgG1	Strong	Yes	High affinity for FcγRI, FcγRII, and FcγRIII
IgG2	Weak	Yes	Limited affinity for FcγR
IgG3	Strongest	Yes	High affinity for FcγRI and FcγRIII
IgG4	Minimal	No	Low affinity for FcγR