IMMUNOGLOBULINS: STRUCTURE, TYPES AND FUNCTIONS - ANATOMY AND PHYSIOLOGY - 2025

The immunoglobulins are molecules produced B cells and plasma cells which assist the defense of the organism. They consist of a glycoprotein biomolecule belonging to the immune system. They are one of the most abundant proteins in blood serum, after albumin.

Antibody is another name for immunoglobulins, and they are considered globulins due to their behavior in the electrophoresis of the blood serum that contains them. The immunoglobulin molecule can be simple or complex, depending on whether it is presented as a monomer or is polymerized.

The common structure of immunoglobulins is similar to the letter "Y". There are five types of immunoglobulins that present morphological, functional and location differences in the body. The structural differences of antibodies are not in shape, but in composition; each type has a specific objective.

The immune response promoted by immunoglobulins is highly specific and a highly complex mechanism. The stimulus for its secretion by cells is activated in the presence of foreign agents to the body, such as bacteria. The role of the immunoglobulin will be to bind to the foreign element and eliminate it.

Immunoglobulins or antibodies can be present both in the blood and on the membranous surface of organs. These biomolecules represent important elements within the human body's defense system.

Structure

The structure of antibodies contains amino acids and carbohydrates, the oligosaccharides. The predominant presence of amino acids, their quantity and distribution is what determines the structure of the immunoglobulin.

Like all proteins, immunoglobulins have primary, secondary, tertiary and quaternary structures, determining their typical appearance.

Regarding the number of amino acids they present, immunoglobulins have two types of chain: heavy chain and light chain. Also, according to the amino acid sequence in its structure, each of the chains has a variable region and a constant region.

Heavy chains

The heavy chains of immunoglobulins correspond to polypeptide units made up of sequences of 440 amino acids.

Each immunoglobulin has 2 heavy chains, and each of these has in turn a variable region and a constant region. The constant region has 330 amino acids and the variable 110 sequenced amino acids.

The structure of the heavy chain is different for each immunoglobulin. There are a total of 5 types of heavy chain that determine the types of immunoglobulin.

Heavy chain types are identified by the Greek letters γ, μ, α, ε, δ for immunoglobulins IgG, IgM, IgA, IgE, and IgD, respectively.

The constant region of the heavy chains ε and μ are formed by four domains, while those corresponding to α, γ, δ have three. So each constant region will be different for each type of immunoglobulin, but common to immunoglobulins of the same type.

The variable region of the heavy chain is made up of a single immunoglobulin domain. This region has a sequence of 110 amino acids, and will be different depending on the specificity of the antibody for an antigen.

In the structure of heavy chains, an angulation or bending can be observed - called a hinge - which represents the flexible area of ​​the chain.

Light chains

Immunoglobulin light chains are polypeptides made up of about 220 amino acids. There are two types of light chain in humans: kappa (κ) and lambda (λ), the latter with four subtypes. The constant and variable domains have sequences of 110 amino acids each.

An antibody can have two κ (κκ) light chains or a pair of λ (λλ) chains but it is not possible for it to possess one of each type at the same time.

Fc and Fab segments

As each immunoglobulin has a shape similar to a "Y" it can be divided into two segments. The "lower" segment, the base, is called the crystallizable fraction or Fc; while the arms of the «Y» form the Fab, or fraction that binds to the antigen. Each of these structural sections of immunoglobulin performs a different function.

Segment Fc

The Fc segment possesses two or three constant domains of the immunoglobulin heavy chains.

Fc can bind to proteins or a specific receptor on basophils, eosinophils, or mast cells, thereby inducing the specific immune response that will eliminate the antigen. Fc corresponds to the carboxyl terminus of immunoglobulin.

Fab segment

The Fab fraction or segment of an antibody contains the variable domains at its ends, in addition to the constant domains of the heavy and light chains.

The constant domain of the heavy chain is continued with the domains of the Fc segment forming the hinge. Corresponds to the amino-terminal end of immunoglobulin.

The importance of the Fab segment is that it allows binding to antigens, foreign and potentially harmful substances.

The variable domains of each immunoglobulin guarantee its specificity for a given antigen; this characteristic even allows its use in the diagnosis of inflammatory and infectious diseases.

Types

By Alejandro Porto, via Wikimedia Commons

The immunoglobulins known up to now have a specific heavy chain that is constant for each of these and differs from the others.

There are five varieties of heavy chains that determine five types of immunoglobulins, whose functions are different.

Immunoglobulin G (IgG)

Immunoglobulin G is the most numerous variety. It has a gamma heavy chain and occurs in unimolecular or monomeric form.

IgG is the most abundant both in blood serum and in tissue space. Minimal changes in the amino acid sequence of its heavy chain determine its division into subtypes: 1, 2, 3 and 4.

Immunoglobulin G has a sequence of 330 amino acids in its Fc segment and a molecular weight of 150,000, of which 105,000 correspond to its heavy chain.

Immunoglobulin M (IgM)

Immunoglobulin M is a pentamer whose heavy chain is μ. Its molecular weight is high, approximately 900,000.

The amino acid sequence of its heavy chain is 440 in its Fc fraction. It is found predominantly in blood serum, representing 10 to 12% of immunoglobulins. IgM has only one subtype.

Immunoglobulin A (IgA)

It corresponds to the heavy chain type α, and represents 15% of the total immunoglobulins. IgA is found in both blood and secretions, even in breast milk, in the form of a monomer or dimer. The molecular weight of this immunoglobulin is 320,000 and it has two subtypes: IgA1 and IgA2.

Immunoglobulin E (IgE)

Immunoglobulin E is made up of the ε-type heavy chain and is very scarce in serum, around 0.002%.

IgE has a molecular weight of 200,000 and is present as a monomer primarily in serum, nasal mucus, and saliva. It is also common to find this immunoglobulin within basophils and mast cells.

Immunoglobulin D (IgD)

The heavy chain variety δ corresponds to immunoglobulin D, which represents 0.2% of total immunoglobulins. IgD has a molecular weight of 180,000 and is structured as a monomer.

It is related to B lymphocytes, attached to their surface. However, the role of IgD is unclear.

Change of type

Immunoglobulins can undergo a structural type change, due to the need to defend against an antigen.

This change is due to the role of B lymphocytes in making antibodies through the property of adaptive immunity. The structural change is in the constant region of the heavy chain, without altering the variable region.

A type or class change can cause an IgM to change to IgG or IgE, and this occurs as a response induced by interferon gamma or interleukins IL-4 and IL-5.

Features

The role that immunoglobulins play in the immune system is of vital importance for the body's defense.

Immunoglobulins are part of the humoral immune system; that is, they are substances secreted by cells for protection against pathogens or harmful agents.

They provide an effective means of defense, effective, specific and systematized, being of great value as part of the immune system. They have general and specific functions within immunity:

General functions

Antibodies or immunoglobulins fulfill both independent functions and activating cell-mediated effector and secretory responses.

Antigen-antibody binding

Immunoglobulins have the function of binding antigenic agents specifically and selectively.

The formation of the antigen-antibody complex is the main function of an immunoglobulin and, therefore, it is the immune response that can stop the action of the antigen. Each antibody can bind two or more antigens at the same time.

Effector functions

Most of the time, the antigen-antibody complex serves as the initiator to activate specific cellular responses or to initiate a sequence of events that determine the elimination of the antigen. The two most common effector responses are cell binding and complement activation.

Cell binding depends on the presence of specific receptors for the Fc segment of the immunoglobulin, once it has bound to the antigen.

Cells such as mast cells, eosinophils, basophils, lymphocytes, and phagocytes possess these receptors and provide the mechanisms for antigen elimination.

The activation of the complement cascade is a complex mechanism that involves the beginning of a sequence, so the end result is the secretion of toxic substances that eliminate antigens.

Specific functions

First, each type of immunoglobulin develops a specific defense function:

Immunoglobulin G

- Immunoglobulin G provides most of the defenses against antigenic agents, including bacteria and viruses.

- IgG activates mechanisms such as complement and phagocytosis.

- The constitution of IgG specific for an antigen is durable.

- The only antibody that the mother can transfer to her children during pregnancy is IgG.

Immunoglobulin M

- IgM is the antibody with a rapid response to harmful and infectious agents, as it provides immediate action until it is replaced by IgG.

- This antibody activates cellular responses incorporated into the lymphocyte membrane and humoral responses such as complement.

- It is the first immunoglobulin synthesized by humans.

Immunoglobulin A

- It acts as a defense barrier against pathogens, by being located on the surfaces of the mucous membranes.

- It is present in respiratory mucosa, digestive system, urinary tract and also in secretions such as saliva, nasal mucus and tears.

- Although its complement activation is low, it can be associated with lysozymes to kill bacteria.

- The presence of immunoglobulin D in both breast milk and colostrum allows a newborn to acquire it during breastfeeding.

Immunoglobulin E

- Immunoglobulin E provides a strong defense mechanism against allergy-producing antigens.

- The interaction between IgE and an allergen will cause inflammatory substances to appear responsible for the symptoms of allergies, such as sneezing, coughing, hives, increased tears and nasal mucus.

- IgE can also attach itself to the surface of parasites through its Fc segment, producing a reaction that causes their death.

Immunoglobulin D

- The monomeric structure of IgD is linked to B lymphocytes that have not interacted with antigens, thus they play the role of receptors.

- The role of IgD is unclear.

References

1. (sf) Medical definition of immunoglobulin. Recovered from medicinenet.com
2. Wikipedia (nd). Antibody. Recovered from en.wikipedia.org
3. Grattendick, K., Pross, S. (2007). Immunoglobulins. Recovered from sciencedirect.com
4. Iáñez, E. (sf). Immunoglobulins and other B cell molecules. Course in general immunology. Recovered from ugr.es
5. (sf) Introduction to Immunoglobulins. Recovered from thermofisher.com
6. Buddiga, P. (2013). Immune system anatomy. Recovered from emedicine.medscape.com
7. Biochemistryquestions (2009). Immunoglobulins: structure and functions. Recovered from biochemistryquestions.wordpress.com
8. (sf) Immunoglobulins - structure and function. Recovered from microbiologybook.org