All Types of Antibody Isotypes Explained: IgG, IgA, IgM, IgE, and IgD

Key Takeaways

• IgG is the most abundant, long-lasting antibody isotype. Also, it is able to cross the placenta for facilitating fetal immunity.
• IgA dominates in mucosal secretions, protecting entry points like the gut and lungs.
• IgM is the first responder in infections, forming pentamers for strong complement activation.
• IgE is vital for allergy responses and defense against helminths, despite low serum levels.
• IgD functions mainly as a receptor on immature B cells and aids respiratory immunity.
• Each isotype has a unique structure, distribution, and half-life.
• Specific subclasses (IgG1–4, IgA1/2) refine functions further.
• Isotype diversity ensures balanced systemic and mucosal immunity.

Immunoglobulins (Ig), known more commonly as “antibodies“, are glycoproteins that are produced by the body’s B lymphocytes and plasma cells as part of the body’s “adaptive immune system”. They are mainly needed to identify and neutralize antigens, be it pathogens such as viruses/bacteria, allergens, or toxins.

All antibodies have a common structural backbone, but vary in terms of the kind of heavy chain constant region that defines the specific isotype.

Human beings have five main isotypes of antibodies: IgG, IgA, IgM, IgE, and IgD. Although all perform the task of antigen recognition, each of the isotypes has specific structural aspects, patterns of distribution, half-lives, interaction with receptors, and immune activity.

We will break each isotype down into specific details, focusing on structure, function, location, and immunological significance.

Immunoglobulin: An Overview

An antibody is comprised of two light chains and two heavy chains, all of which are identical, and forms a Y-shape. The top tips of the Y has variable regions, which are the parts that bind to/recognize antigens, and the constant regions, which make the lower “stem” of the Y and determine the isotype of the antibody.

Key Parameters Differentiating Isotypes

Isotype	Heavy Chain Type	Serum %	Average Half-Life	Primary Location	Notable Function
IgG	γ (gamma)	~75%	21 days (IgG1, IgG4), ~7 days (IgG3)	Serum, extracellular fluids	Secondary immune response, opsonization, placental transfer
IgA	α (alpha)	~15%	6 days	Mucosal secretions, breast milk, saliva	Mucosal defense, neutralizing pathogens at entry points
IgM	μ (mu)	~10%	5 days	Blood, initially released in the lymphoid tissues	First antibody produced, complement activation
IgE	ε (epsilon)	<0.01%	2 days	Bound to mast cells and basophils	Allergy, parasitic infection immunity
IgD	δ (delta)	<1%	3 days	Surface of immature B cells, respiratory tract	Acts as a B-cell receptor and modulates activation

IgG: The Workhorse of The Immune System

The predominant antibody in serum and in extracellular fluid is IgG. It constitutes approximately 75% of all immunoglobulins in the body at any one time.

Structural Features

• Monomeric with two antigen-binding sites.
• Four subclasses: IgG1, IgG2, IgG3, IgG4. All of them differ in the length of the “hinge” region and their capacity to induce complement system or bind Fc receptors.
• The longest hinge region is IgG3, which also has the shortest half-life (approximately 7 days).

Major Functions

• Dominance of secondary response: IgG is produced in huge amounts when the body is exposed to the same antigen in subsequent exposures.
• Opsonization: Attaches Fc receptors to phagocytes in order to encourage ingestion.
• Complement activation: IgG1 and IgG3 in particular activate the classical complement pathway.
• Antiviral and antibacterial activity: Neutralizes toxins and prevents pathogen adherence.
• Placental transport: Passive immunity of the baby only via its ability to cross the placenta (through neonatal Fc receptor, FcRn).

Subclass Specialization

Subclass	Serum Proportion	Half-Life	Complement Activation	Role
IgG1	~65% of IgG	21 days	Strong	Response to protein antigens
IgG2	~23%	21 days	Weak	Response to polysaccharide antigens (e.g., bacterial capsules)
IgG3	~7%	~7 days	Very strong	Excellent complement activator
IgG4	~4%	21 days	None	Involved in chronic exposure, allergen tolerance

IgA: The Mucosal Guardian

IgA constitutes approximately 15% of serum antibodies; however, more significantly, it is the predominant immunoglobulin in the body’s mucosal secretions.

Structural Features

• Exists in monomeric (serum IgA) and dimeric (secretory IgA, sIgA) forms.
• The secretory component (SC) shields IgA against enzymatic destruction in severe mucosal environments.
• Two subclasses: IgA1 (dominant in serum) and IgA2 (dominant in secretions like intestine, saliva).

Critical Functions

• Mucosal defense: Neutralizes pathogens at entry sites (gut, respiratory tract, urogenital tract).
• Non-inflammatory response: Does not cause severe stimulation of complement; does not cause much damage to tissues in the mucosa.
• Immune exclusion: Prevents microbial adhesion to epithelial cells.
• Neonatal immunity: Acquired through the transfer of breast milk to infants, which coats the gut surfaces in infants.

IgM: The First Responder

Approximately 10% of total serum antibodies is composed of IgM, but it is actually the first antibody isotype that is produced upon exposure to the antigen.

Structural Features

• Exists as a pentamer in circulation, with 10 potential antigen-binding sites.
• J-chain links monomers in a pentameric structure.
• IgM is limited to the intravascular compartment largely by its large size.

Major Functions

• Primary response preeminence: First antibody isotype produced upon infection.
• Firm complement activation: Excellent triggering of the classical pathway, which is made possible by the pentameric structure.
• Agglutination: Valency is high, so the pathogens can be properly “clumped”.
• B cell receptor (BCR): IgM is membrane-bound and monomeric before the class switching stage of immature B cells.

IgE: The Allergy and Parasite Mediator

The least prevalent is IgE (<0.01% of serum immunoglobulins, approximately 50-200 ng/mL), but disproportionately important in allergic disease and parasite resistance.

Structural Features

• Monomeric structure
• Mast cells and basophils have high-affinity Fc epsilon RI receptor binding, resulting in prolonged tissue half-life (although plasma half-life is relatively short, ~2 days).

Critical Functions

• Allergic reaction: Binding of the allergen to IgE on the mast cell causes cross-linking of IgE, releasing histamine, leukotrienes, and cytokines

Cynthia

Cynthia Lee is the President of AAA Biotech and specializes in understanding highly validated and characterized monoclonal/polyclonal antibodies, recombinant proteins, and ELISA kits.