ABO Genetic Pathway

I've been pondering how to add stuff to this site and thought that the best way is to talk about the new images that I produce as and when I make them for lectures and whatnot.

Let's start at the beginning then. The ABO blood goup system. I'm still amazed to think that it all stems down to three genes and a few sugars - people die every year when we get it wrong yet so few peoplw understand the ABO blood group system. You've got your three genes A, B and H (note the itlaics for genes) and everything depends on how these come together.

A lot of it depends on having this precursor substance changed to the H antigen which is done by sticking a fucose sugar on it - simple but effective. This means that the structure can now be recognised by the "A transferase" (galNAc transferase) or the "B transfersase" (galactose transferase) which stick on an extra sugar from a carrier molecule onto the the H gene and turn it into an A antigen or a B antigen respectively. These enzymes are doing this all over the red blodd cell with all of the H antigens they can find. This means that there will always be some unchanged H antigen on the cells as well as A / B antigens - A transferase is a "better" enzyme than "B transferase" so more H is converted to A than H converted to B antigen. Those of us who are group O (hurrah for us) don't have the A transferase or the B transferase so all of our H remains unconverted - when he discovered the groups Landsteiner called this group "0" (zero) because it didn't react and this became our modern group "O". The smaller number of people who have both the A and B genes, make A transferase and B transferase, have both enzymes converting some H antigen into A antingen and some H antigen into B antigen - they therefor have both A and B (and a tiny bit of H) on each cell - they are group AB. Please note that each cell has A and B antigens on it - group AB people do not have some red cells which are A and others which are B.

Just a quick note for those very few people around the world who don't have the H gene. These people cannot change the presursor substance into the H antigen so it doesn't matter whwther or not the have the A transferase or B tranferase - the enzymes will not recognise the unchanged precursor substance as a substrate so can't trasform it into A or B antigens - everything stops at the presursor substance. this blood group is called Bombay and has serious implications in the transfusion of blood - they can't receive group A, B, AB or O blood!

Note
H isn't really in the ABO blood group system because it's genes are located on a different chromosome which is against one of the definitions of antigens in a blood group ststem - they shaild all be together on the same chromosome. This is a bit ripe though because the genes should code for the antigens to make it a blood group system - in the case of ABO the genes code for the transferases which change H into A and/or B so that doesn't fit either!

Size Doesn't Matter!

One of the things I come across is that IgM antibodies can't cross the placenta.

True!

But why does everybody think that it is because it is too big?

Think about it - how do all of those really big fat molecules (that's molecules of fat rather than obese molecules) or hormones or any other large molecules get across the placenta if IgM can't because of its size? It's all to do with receptors and transporters on the placenta.

IgM can't cross the placenta because there are not the recptors on the placenta.

Compartmentalisation

Wow! Big word to start off on.

I was speaking with a group today and one of the main problems in learning anything (including Transfusion Science) is that we compartmentalise eveything - we split up all of our learning into neat little (one-hour) bundles of knowledge.

What we don't do is generalise things - we know about antibody classes because we learned that in the Basic Immunology class but we then have to re-learn it when we are talking about Haemolytic Disease of the Fetus and Newborn or discussing the clinical significance of red cell antibodies. This is too simplistic - we don't have to learn everything de novo each time but we do fail to grasp that the properties of antibodies learned in one class realtes to topics covered in other classes.

This is a huuuuge waste of time and effort!

Windy's Advice

When you get home from classes / lectures read your notes and try and generalise a bit more - have a guess where the things you've learned may pop up in future learning - you could well be wrong but it won't hurt to try - sometimes you'll be right! Then you'll have a jump start on the rest of the class!
Incidentally, by doing this you'll be automatically reflecting on your learning - we all hate doing that but this is a way of reflecting which can obviously benefit you!