Antibody

Antibodies, also known as immunoglobulins, are large Y-shaped proteins belonging to the immunoglobulin superfamily. They are central components of the immune system and play a crucial role in identifying and neutralising foreign substances, known as antigens. These antigens may include pathogenic bacteria, viruses and other molecules capable of triggering an immune response. Each antibody is highly specific, binding only to one or a few closely related antigens through a precise lock-and-key interaction.
Antigen refers to any substance that stimulates the production of a specific antibody. Each arm of the antibody’s Y-shaped structure contains a paratope, the binding site that recognises a corresponding epitope on the antigen. This interaction allows antibodies to label pathogens or infected cells for destruction by other immune components or to neutralise them directly, for example by blocking viral entry into host cells.
Antibodies may circulate freely in body fluids or exist as receptors on the surface of B cells. Although antibody often refers to the secreted form and immunoglobulin may refer to both secreted and membrane-bound forms, the two terms are frequently used interchangeably.

Classes and Distribution

To recognise millions of different antigens, antibodies vary extensively at their antigen-binding sites, while the remainder of their structure is comparatively conserved. Humans produce five major antibody classes: IgA, IgD, IgE, IgG and IgM. Some classes have subclasses, such as IgG1–IgG4 and IgA1–IgA2. These classes differ in their effector functions, locations in the body and timing during an immune response. Although the naming of classes is shared across species, functions may differ; for instance, mouse IgG1 functionally resembles human IgG2 rather than human IgG1.
Antibodies in body fluids form part of humoral immunity, distinct from cell-mediated immunity associated with T cells. While typically classified as adaptive immune molecules, some antibodies—particularly natural IgM produced by B1 cells—have features that blur this distinction. Natural IgM is polyreactive and can recognise multiple unrelated antigens, contributing to early immune defence in cooperation with the complement system.
Despite this overlap, antibodies are generally considered products of the adaptive immune system because they exhibit high specificity, are generated through gene rearrangement processes and contribute to immune memory.

B-Cell Differentiation and Immune Memory

During an immune response, B cells differentiate into antibody-secreting cells or memory B cells. Antibody-secreting cells include plasmablasts and plasma cells. Plasmablasts divide rapidly and are short-lived, typically arising early in an immune response outside germinal centres. Plasma cells, in contrast, are terminally differentiated, do not divide and depend on specialised survival niches to persist.
Plasma cells release large quantities of antibodies independently of antigen presence, maintaining baseline immunity as long as they survive. Long-lived plasma cells, often housed in the bone marrow or mucosal tissues, can persist for many years and are key to durable immunity. Their antibody production can be modulated by immune signals, including those induced by adjuvants.
Memory B cells, which may persist for decades, are primed for rapid reactivation upon re-exposure to a familiar antigen. They undergo further affinity maturation and class switching during secondary responses. This adaptive feature helps counter pathogens that mutate frequently: while long-lived plasma cells cannot modify their antibodies, memory B cells generate improved antibodies upon renewed antigen encounter.

Role in Vaccination and Protection

Antibodies are central to the protective effects of most vaccines. Long-term protection depends on sustained antibody levels, supported by long-lived plasma cells. However, pathogens capable of rapid mutation, such as certain viruses, may escape existing antibodies. In such cases, memory B cells enable adaptation to new variants, providing ongoing defence.
Although antibodies are vital, they are not the only essential immune component in all infections. Some diseases rely more heavily on cell-mediated immunity, as seen in viral infections like shingles.

Structure

Antibodies are approximately 150 kilodaltons in mass and about 10 nanometres in size. Each antibody consists of four polypeptide chains: two identical heavy chains and two identical light chains connected by disulphide bonds. These chains are organised into repeating domains of roughly 110 amino acids.
Light chains contain one variable and one constant domain, while heavy chains contain one variable domain and three or four constant domains depending on the class. Structurally, antibodies are divided into two major fragments:

• Fab (Fragment antigen-binding): Contains the variable regions responsible for antigen recognition.
• Fc (Fragment crystallisable): Forms the stem of the Y-shape and mediates effector functions by interacting with immune cells and complement proteins.

A flexible hinge region connects these parts, enabling antibodies to bind antigens positioned at varying distances and to form multi-protein complexes.
In protein electrophoresis, antibodies migrate primarily in the gamma globulin region. Historically, gamma globulin was used synonymously with immunoglobulin, though this terminology is no longer preferred.

Antigen-Binding Site

The antigen-recognition region, known as the Fv region, contains the antibody’s variable domains. Within each variable domain are three hypervariable loops—the complementarity-determining regions (CDRs). These loops form the antigen-binding site and determine specificity. Their shape can form pockets, grooves or extended surfaces, enabling the binding of antigens of diverse shapes and sizes.
Together, the six CDRs from the heavy and light chains create a unique binding site, allowing antibodies to recognise an extraordinary range of molecular structures with exceptional precision.