The immune system is responsible for fighting pathogens and the diseases they cause. To do this, it basically uses two types of mechanisms, one is innate immunity and the other is acquired immunity.
Innate immunity encompasses the action of cells and immune mechanisms that defend the body against infections in a non-specific way. In contrast, acquired immunity encompasses cells and specific defense mechanisms against a particular pathogen or group of related pathogens.
Within acquired or specific immunity, there is cell-mediated acquired immunity, carried out by specific lines of lymphocytes or T cells, and acquired antibody-mediated immunityalso called humoral immunity.
The antibodies are protein molecules of the family of immunoglobulins (Ig) which are produced by B lymphocytes mature and differentiated into plasma cells plasma cells.
Each antibody is produced to specifically recognize a molecule present in a certain pathogen, which is why it is considered a specific immune response. In addition, the production of the antibody requires prior contact with the pathogenic agent, hence it is said to be a type of acquired immunity.
In the human immune system there 5 major types of antibodies (isotypes) which differ at the molecular and structural level, but also in the type of immune response they produce and at the time they intervene during the period of fighting a disease.
In alphabetical order, the five types of antibodies are:
- IgA
- IgD
- IgE
- IgG
- IgM
These five types of antibodies are shared by all mammals, they are not exclusive to the human species, but other types of immunoglobulins can be found in other animals. For example, IgY in birds and reptiles, or IgW in elasmobranchs (sharks and rays).
Next we will see what is the general structure of immunoglobulins and what are the most important characteristics and differences of each type of antibody.
General structure of antibodies
Although there are several classes of antibodies, they all share a similar general structure. Chemically they are glycoproteinssince they have a protein part and a carbohydrate part, which can exceed 150 kDa in mass and 10 nm in length.
The protein part is a globulin in the form of Y formed by four chains, two heavy and two lightwhich in humans can be several types:
- light chains (2): lambda (λ) and kappa (κ).
- Heavy chains (5): alpha (α), delta (δ), epsilon (ε), gamma (γ), and mu (μ).
The chains are linked together by disulfide bonds and depending on the combination of light and heavy chains, different types of antibodies are formed, but each Ig always has two identical heavy chains and two identical light chains.
In both light and heavy chains there is a zone that remains constant within the same type of antibody, and another zone that is variable, sometimes called hypervariable zone. The variable area or domain is the one that interacts with the antigen, and that is precisely why it is so variable, in order to be able to synthesize specific molecules for each antigen.
In light chains there is a variable domain and a constant domain, while in heavy chains there may be two or more constant domains. For example, the ε-type heavy chain has 1 variable domain and 4 constant domains.
The described molecule would form a monomer or immunoglobulin unit, but the active form of some types of antibodies are polymers made up of several units. For example, IgA usually forms dimers and IgM usually forms pentamers.
Regions
In addition to the light and heavy chains, and the constant and variable domains within each chain, other structural and functional regions are distinguished in each immunoglobulin unit:
- Fab Region: encompasses the variable domains and constant domains that form the arms of the “Y”. Also known as antigen binding region (antigen bindinghence the name "ab").
- Fv Region: is formed by the combination of a light chain variable region and the adjacent heavy chain variable region. It includes only the variable domains located at the ends of the arms of the «Y».
- FC Region: the tail of the "Y" is formed and includes only heavy chain constant domains. It does not include the constant domains of the Fab region.
Types of antibodies
The antibodies of our immune system are classified into 5 classes or isotypes. Some isotypes have multiple subtypes.
Each isotype is named with the acronym “Ig”, for immunoglobulin, and a certain letter depending on the type of heavy chain they have:
- IgA type heavy chains alpha (α)
- IgD type heavy chains delta (δ)
- IgE delta-type heavy chains epsilon (ε)
- IgG delta-type heavy chains gamma (γ)
- IgM mu-type heavy chains (μ)
IgA
The IgA It's formed by alpha-type heavy chains and has four antigen-binding sites. There are two structural subtypes, IgA1 and IgA2. In IgA2, the alpha heavy chains are not linked by disulfide bonds, but rather through noncovalent molecular interactions.
IgA is mucosal characteristic such as the digestive, respiratory, and urogenital tracts, and in secretions such as saliva, tears and breast milk. Here it is known as Secretory IgA (sIgA) and most of it is found in polymeric form of between 2 and 4 monomers, but the most abundant is dimerwith two IgA bound.
In circulation it is known as serum IgA and it occurs mainly in the form of monomers. IgA1 and IgA2 can be present in both serum and secretions, but IgA1 is usually the predominant subtype. The difference between serum IgA and secretory IgA is that secretory IgA has an oligosaccharide added by mucosal epithelial cells during secretion.
Under normal conditions, serum IgA represents approximately 13% of all serum antibodies. 80% of serum IgA is type IgA1 and 20% type IgA2. In mucous membranes and secretions, IgA2 can reach 35%.
Function
Secretory IgA plays a crucial role in the function of the mucosal immune system, where it acts as a first line of defense against infection. By passing through the milk, IgA contributes to the baby's immune system while your immune system matures.
In circulation, IgA interacts with CD89 effector T cell receptors to initiate an inflammatory response involving antibody-dependent cytotoxicity, eosinophil and basophil degranulation, monocyte, macrophage, and neutrophil activation, and increased polymorphonuclear activity in the respiratory system.
IgD
The IgD It is made up of immunoglobulins delta-type heavy chains and occurs in the form of monomers of approximately 185 kDa.
IgD stands for less than 1% of total serum antibodies and almost all of it is found as a membrane receptor in B cells that have not been activated. IgD is usually coexpressed on the surface of these lymphocytes together with membrane IgM.
In free form in the serum it hardly represents 0.25%.
Function
Its exact function is not well understood, but it seems to be related to the activation and differentiation of B lymphocytes into plasma cells. IgD has also been found bound to receptors on basophils and mast cells, so it could participate in the activation of these cells.
IgE
The IgE It's formed by epsilon-like heavy chains. It is produced in the form of monomers of approximately 200 kDa.
It is the type of antibody least abundant of all, only represents 0.02% of serum immunoglobulins under normal conditions. It is found in greater quantity in the mucous membranes of the respiratory and intestinal systems.
Function
IgE offers immune protection against potential pathogens in gastrointestinal and respiratory mucosaespecially against parasitic worms, for example against helminths.
Also known as reaginic antibody for being involved in hypersensitivity reactions and allergic reactions.
The antigen binding sites bind to membrane receptors on basophils and mast cells, the immune cells that produce the typical symptoms of hypersensitivity reactions, specifically the type 1 hypersensitivity reaction that manifests in diseases such as allergic asthma, sinusitis, or allergic rhinitis.
IgG
The IgG It is made up of immunoglobulins gamma-like heavy chains. It is produced in the form of monomers with a molecular weight of around 150 kDa.
It is the type of antibody most abundant of all, representing between 75 and 80% of the antibodies in the blood serum. It is also the majority in the extracellular fluid.
There are four subtypes, IgG1, IgG2, IgG3 and IgG4. The most abundant of all is IgG1. Types IgG3 and IgG4 are the only two antibodies capable of cross the placenta and provide protection to the fetus.
Function
IgG, being the majority in circulation, offers protection against pathogens in almost all tissues and organs. It is also the only antibody that protects the fetus.
IgG activates the classical pathway of complement system, a part of the immune system that enhances antibody and phagocytic cell responses against pathogens and damaged cells. It is also one of the most active antibodies in the opsonizationwhich consists of coating pathogens with antibodies to attract macrophages.
It has an important role in Antibody-mediated cytotoxicity and antibody-mediated intracellular proteolysis. Furthermore, IgG is associated with type II and type III hypersensitivity reactions.
IgM
The IgM is the immunoglobulin formed by mu-type heavy chains. It is the largest antibody produced by the human immune system, as the most abundant free form is a pentamer of 5 units of IgM which can exceed 900 kDa molecular weight.
It is also produced as membrane immunoglobulin in the form of monomers, only secreted IgM form the pentamers.
Function
IgM is co-expressed with IgD on non-activated B lymphocytes. assist in antigen recognition. It also intervenes in the opsonization and agglutination of pathogens and activates the complement system.
It is the type of antibody that occurs faster after contact with a pathogen, which is why it is the main antibody in the primary humoral response. Depending on the type of stimulus, active B lymphocytes will switch to IgG, IgA or IgE isotypes, in the secondary humoral response.