Antibody diagram
Diagram of an Antibody
An antibody molecule consists of two heavy protein chains (blue and light blue) combined with two light chains (green and light green).The two heavy chains are identical to one another and the two light chains are identical to one another, also. (An exception would be NovImmune’s kappa lambda-body.)

The chemical structure of the protein chains is divided into 12 areas, or domains (pale blue and pale orange ovals).

The heavy chains each consist of three constant domains (CH1,CH2, and CH3) and one variable domain (VH). The light chains each consist of a constant domain (CL) and a variable domain (VL).

The Fc (Fragment crystallisable) region, or “tail,” of the antibody is the part of the molecule which binds to receptors on the surface of cells like macrophages, neutrophils, and NK-cells.

The antibody attaches itself to a complementary, or matching, antigen at its antigen binding sites, located at the ends of either of its two arms, or Fab regions (Fragment antigen binding).

While shown outside of the domain areas for purposes of this illustration, the amino acid loops making up the Complementary Determining Regions (CDRs) are actually part of the variable domains (VL and VH).

There are three CDR loops per variable domain (L1L2L3 on the light chains and H1H2H3on the heavy chains), for a total of 12 loops for the antibody as a whole.

These loops act similarly to the fingers of a hand to grab and hold antigens. The specific size and shape of the CDRs determines to which antigens the antibody can and will bind.



On the front line of human immune defense

Antibodies are large Y-shaped protein molecules created by the immune system to identify and neutralize foreign objects and pathogens, such as bacteria, viruses, fungi, parasites, and toxins. Also known as immunoglobulin, antibodies are manufactured by white blood cells called B-lymphocytes, or B-cells.

During prenatal and neonatal stages of life, antibodies are provided to the fetus or infant through passive immunization by the mother. The ability for the infant’s immune system to independently develop antibodies then develops during the first one or two years of life.

It is estimated that humans are capable of generating about 10-billion different kinds of antibodies, primarily by varying the amino acid composition of the protein molecule. Each type of antibody defends the body against a specific type of antigen.

While most antibodies are created in response to particular antigens, the immune system also produces “natural antibodies” that have not been in response to antigen exposure, immunization, or vaccination. These natural antibodies travel through the blood and react mainly to carbohydrates found on the surfaces of bacteria, beginning an immune response without having to activate the adaptive immune system.

How Antibodies Work

Antibodies function in three distinct ways. They bind directly to antigens, effectively coating the surface of the invader, in order to prevent pathogens from entering or damaging healthy body cells. Antibodies can also stimulate other parts of the immune system (e.g. complement proteins) to destroy the pathogens. And, antibodies can mark pathogens through a process called opsonization so that the pathogens can be identified and neutralized by other immune cells.


A principal way that pathogens are destroyed is through phagocytosis. In this process, white blood cells like macrophages, neutrophils, and dendritic cells destroy invading micro-organisms by surrounding them, drawing them inside their own membranes, and then neutralizing them with enzymes. They are said to literally “eat” the invaders.

The problem is that the membranes of phagocytes and invading cells both carry a negative charge, so they naturally repel one another. The antibody bridges that gap by attaching (“binding”) itself to the antigen with one of its antigen binding sites, and linking to the phagocyte with its “tail,” or Fc region. This serves to neutralize the charge and bring the antigen and phagocyte into proximity. The antibody can also activate the phagocyte, making it a much more hungry and effective eater.

Antigen binding

The antigen binding site of an antibody is located at the top of each of the two outstretched arms. Each site is defined by 6 loops called Complementary Determining Regions (CDR). Three are found on the heavy chain (H1, H2, and H3) and 3 on the light chain (L1, L2, and L3). These protein loops mirror, or complement, the shape of specific antigens. As a result, they determine to which specific antigens the antibody can and will bind.

Antibody Classes

There are five classes, or isotypes, of antibodies — IgA, IgD, IgE, IgG, and IgM. Each isotype is uniquely suited to defend against different types of invaders. The constant region of the antibody determines both its class and function.

Immunoglobulin alpha (IgA) is found in mucosal areas of the body including the digestive, respiratory, and reproductive tracts. IgA is also present in saliva, tears, and breast milk, where its function is to coat the baby’s intestinal mucosa to protect it from pathogens.

Immunoglobulin delta (IgD) appears in very small amounts in the blood, but is mainly found as receptors on B-cells which have not yet encountered antigens, where its function is to activate the B-cell.

An antigen is a foreign molecule which triggers the production of antibodies by the immune system (antibody generator).

An allergen is an antigen that can cause an allergic reaction.

When an antibody stimulates a immune cell to be a more effective killer, the process is calledantibody-dependent cellular cytotoxicity, or ADCC.

T-helper (Th) cells are white blood cells which activate and mediate the activities of other immune system cells.Immunoglobulin epsilon (IgE) is involved in defending the body against parasites and allergens. Consequently, it is often found attached to mast cells and basophils, although eosinophils, monocytes, macrophages, and blood platelets also have IgE receptors.

Immunoglobulin gamma (IgG) makes up about 75% of the antibodies found in the blood. IgG can bind with many types of pathogens, including bacteria, viruses and fungi. It is the only antibody that can pass through the placenta from mother to fetus, providing in uteroprotection.

Immunoglobulin mu (IgM) helps complement proteins to attack invaders by providing a bridge to which the proteins can attach themselves to an invader in order to begin their complement cascade.

Class switching

Initially, B-cells express only IgD and IgM antibodies. The class is determined by the the constant region (Fc) of the heavy chain. As B-cells mature, they can switch to one of the other classes of antibody (IgA, IgE, or IgG) by replacing the tail region of the antibody. The type of class switching happens in response to the chemical messengers, or cytokines, which the B-cell encounters in its environment.

Somatic hypermutation

In addition to changing the Fc region through class switching, B-cells can also change the antigen-binding (Fab) sections of their receptors through a process called somatic hypermutation. This ess
entially fine-tunes the B-cell to have a higher affinity for binding to its cognate antigen. Somatic hypermutation occurs in response to cytokines presented by T-helper (Th) cells.


Sometimes, the immune system mistakenly recognizes the body’s own healthy tissues as harmful substances and produces antibodies in response. These antibodies, known asautoantibodies, have been implicated in a number of autoimmune disorders including lupus erythematosus, Grave’s disease, and Hashimoto’s thyroiditis, among others.


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