Summary of Selective immunoglobulin A deficiency
Transcript for Selective immunoglobulin A deficiency
Selective immunoglobulin A deficiency
Selective immunoglobulin A deficiency is a condition where there’s a lack of immunoglobulin or antibody A, called IgA for short.
It’s called “selective” because all the other antibody classes, IgM, IgG, IgE and IgD are produced normally.
IgA is in charge of protecting the mucosal surfaces of the body against foreign invaders, so without it, there’s a higher risk of mucosal infections.
B cells make antibodies, and normally, B cells are “born” in the bone marrow, the spongy tissue inside some bones of the body.
This is where they develop their B cell receptors on their surface which eventually can get released - and when they’re freely floating in the blood they’re called antibodies.
Antibodies are Y- shaped protein molecules, formed by two heavy and two light chains, each of which has a variable region, at one end, and a constant region (C region) at the other end.
Variable regions are unique to each B cell and they are designed to bind to a very specific antigen, whereas C regions determine the antibody class.
Initially all of the B cells, have IgM and IgD class antibodies on their surface, with each B cell recognizing and binding to its own unique antigen.
Mature B cells leave the bone marrow and migrate to peripheral lymphoid organs, like the spleen, lymph nodes or mucosa-associated lymphoid tissue, which is also called MALT.
MALT is composed of clusters of lymphoid tissue scattered under the mucous membranes lining the mouth, airways, and digestive tract.
This is a really strategic position, because a variety of antigens are constantly being picked up and filtered from these body tissues.
As a result, B cells are likely to encounter an antigen they recognize.
A bit like spending time at a train station during rush hour to look for someone that catches your eye.
If two of a B cell’s receptors bind to the same antigen, they can cross-link - meaning that two adjacent receptors on the B cell surface can get pulled close together.
When that happens the B cell will often take in the antigen, digest it, and present pieces of it on a another cell surface protein called a major histocompatibility class II molecule, or MHC class II.
If a nearby T cell receptor recognizes this antigen bound to an MHC class II molecule, the T cell begins to get activated.
The specific set of cytokines received by the B cell determine how it class-switches, meaning whether it switches from making IgM and IgD to making IgG, IgE or IgA.
In class switching, what changes is only the constant region, and not the variable region of the antibody, meaning that the antigen specificity remains the same.
IgA is primarily produced when B cells are stimulated by interleukin- 5 (IL-5) or transforming growth factor- β or TGF- β.
Class switching to IgA usually happens in mucosa-associated lymphoid tissue, or MALT, from where IgA is secreted into the saliva, sweat, or intestinal juices.
When IgA is secreted, it’s called secretory IgA, and it’s a dimer, meaning that two IgA molecules are joined together by a joining chain or J chain.
This J chain is recognized by a poly-Ig receptor on the basolateral side of the mucous membrane, which helps it move across the epithelial cells and into the lumen.
Since that’s a very hostile environment, a portion of this receptor, known as secretory component, wraps around IgA like a protective armor and keeps it from getting broken down by degradative enzymes.