Content Reviewers:Rishi Desai, MD, MPH
The immune response is highly specific for each invader, and that’s because the cells of the adaptive immune response have unique receptors that are able to differentiate friendly bacteria from potentially deadly pathogens from their unique parts - called antigens.
The key cells of the adaptive immune response are the lymphocytes - the B and T cells.
The B cell receptor is essentially an antibody except that has a transmembrane part that goes through the membrane attaching the receptor to the surface of the B cell.
The B cell receptor, has two heavy chains and two light chains, and the region or fragment of the B cell receptor that binds the antigen is called the fragment-antigen binding or Fab region.
The Fab region is where the ends of the heavy and light chains meet, and there are two Fab fragments on each B cell receptor.
The remainder of the heavy chain makes up the constant region or constant fragment region, also called Fc.
The two heavy chains are linked to one another by disulfide bonds and each heavy chain is also linked to a light chain by a disulfide bond.
Each B cell receptor, has two identical heavy and light chains, resulting in two identical antigen binding sites.
As the B cell develops into a plasma cell, the B cell receptor gets secreted as an antibody with the exact same antigen specificity.
However, the heavy chain actually changes as the B cell develops.
These five are encoded by heavy chain genes which are referred to by the greek letters mu, delta, gamma, alpha, and epsilon.
Each of these immunoglobulins has a different function, shape, and consequently valence.
The valence of an antibody is the amount antigen binding or Fab fragments it has.
Immunoglobulin M, or IgM, is the first antibody response made in all immune responses.
It makes up approximately 4% of the immunoglobulin found in the serum.
This is because it serves as the the B cell receptor, and like a transformer, it has two completely different conformations.
When it’s serving as the B cell receptor it’s a monomer, and it has a valence of 2 meaning that it has two Fab regions.
When IgM is secreted from a plasma cell it joins up with four other identical IgM antibodies, making a total of 5 antibodies that form a pentamer that’s held together by a J or joining chain.
The J chain is a 15 kDa polypeptide chain that promotes the polymerization of the pentamer by covalently linking to the cysteines of the tails of the Fc regions of the IgM molecule.
Because it’s a pentamer, secreted IgM has a valence of 10.
IgM is the first type of antibody produced in a primary immune response, meaning the first time you see a pathogen.
Finally, IgM is the most effective antibody at activating the complement pathway which is particularly helpful in fighting bacterial infections.
IgG is the most abundant immunoglobulin, making up 75% of the immunoglobulin found in serum!
The IgG molecule is a monomer made up of two gamma heavy chains and two light chains, so its valence is 2.
The most important role of IgG is to serve as an opsonin, and in general opsonins are terrific because they help phagocytes get a firm grip on bacteria.
Normally, bacteria have an antiphagocytic capsule which makes them slippery and hard to grab.
Opsonization is the process by which pathogens are coated with molecules so that they can be more easily picked up and eaten by phagocytes.
Imagine trying to pick up a slippery meatball with your fingers versus stabbing it with a fork and then just having to pick up the fork. Opsonization also makes it easier to eat meatballs faster too.
In this case, IgG is serving as that fork, and the phagocyte has a receptor for IgG, knows as Fc gamma receptor, which allows it to bind to - or hold the fork.
IgG is also great at activating the classical complement pathway, which helps destroy extracellular pathogens like bacteria.
For intracellular pathogens, like viruses, IgG works with natural killer cells to perform antibody dependent cell mediated cytotoxicity, or ADCC.