In order to answer this question, you need to have a basic understanding of the nuts and bolts of the Human Leukocyte Antigen ("HLA") system. If you are already up to speed on HLA, feel free to just skip ahead to the next paragraph. The HLA system is composed of a group of antigens present on your body's cells and tissues. The body has its own unique make-up of HLA antigens that are the main way that the body defines self (i.e., "I have these antigens, therefore, this is me") versus non-self ("I don't have these other antigens, therefore, this is not me").
HLA genes come in two main types: Class I (HLA-A, HLA-B, and HLA-C genes) and Class II (HLA-D genes of several types). These genes are carried on chromosome 6 and are so close together (i.e., they are "linked") that they are inherited in discrete groups, known as "haplotypes" (in other words, you get one copy of chromosome 6 from one parent containing one complete group of HLA genes, and another copy from the other parent, with another group). The final combination of HLA genes you inherit from your parents defines your HLA "genotype", and the combination of antigens that are present on your cells as a result define your HLA "phenotype", or "this is me." The mode of inheritance of HLA genes is illustrated at left, with each parent giving one copy of chromosome 6 (with its group of HLA genes) to a child; a blue one from Dad and a green one from Mom (note that the child could just as easily have inherited a red haplotype from each parent, or a blue one from Dad and a red one from Mom, etc.).
Still with me? As you can see from the figure above, there are only four different combinations of haplotypes that can be inherited. 
So, siblings would have a one-in-four (25%) chance of being HLA identical (though that is not our main concern here today). This is illustrated in the figure on the left, where we see all four of the possible combinations from two parents. When someone inherits the exact same combination of HLA genes from each parent (i.e., they get two copies of the same haplotype), they are said to be "HLA homozygous. " On the other hand, if they get two haplotypes that are not identical, then they are "HLA heterozygous." Notice that Child 1 in the figure is HLA homozygous, with identical HLA genes coming from both Dad and Mom. The other kids are HLA heterozygous, since they received non-identical HLA genes from each parent.
You will notice that I am not going into any detail about the HLA genes here (for example, describing the actual gene combinations in our hypothetical family). I have avoided those details deliberately, primarily because I am choosing to illustrate the concept in as simple a way as possible. If you want more "meat" on HLA, check out chapter 17 in the 14th edition of the AABB Technical Manual for a great summary.
— Blood Bank Guy
Next, let's re-visit what happens when two people that are not HLA-identical get matched as blood donor and blood recipient. As mentioned in another FAQ, in that scenario, our bodies rely on the recognition of foreign HLA antigens on transfused lymphocytes to mount a "counterattack" against transfused white blood cells and neutralize their effect 
(if you haven't read that other FAQ, by the way, please take a minute to go there and check it out; it will really help you understand this one better!). The concept from the other FAQ that illustrates the body's normal response is illustrated in the top part of the figure on the right. If the body doesn't recognize the transfused lymphs as foreign, then the situation that is illustrated in the bottom part of the figure can occur, where the foreign lymphs mount an immune response against the recipient's tissues. This is a perfect set-up for the horrendous and usually fatal transfusion complication known as "Transfusion-associated Graft-vs-Host Disease", or "TA-GVHD."
If these two concepts (HLA inheritance and the body's response to transfusion) don't make sense, you should go back up to the top and take a few minutes to really understand what I am talking about. The rest of this stuff will be nonsense to you if you don't have a good handle on these concepts. You can also check out the chapter in the AABB Technical Manual that I mentioned. If you are ready to go on, though, let's do so!
— Blood Bank Guy
The scenario I described above relates to what happens when a recipient is immunosuppressed. Obviously, in family member transfusions, immunosuppression is not generally the rule. So, why would we need to irradiate blood coming from a family member? Let's take a look at our family that we showed in the second figure above and imagine two different scenarios.
First, let's imagine what would happen if Child 2's blood was infused into Child 1. In other words, let's describe what would happen if an HLA-heterozygous donor's blood was infused into an HLA-homozygous recipient. This is illustrated in the figure below:
Child 2's transfused lymphocytes are going to "look around" (OK, OK, they don't really "look"!) in Child 1's body and compare his own HLA antigens with that of Child 1. When that happens, all Child 2 sees in the recipient are HLA antigens that he shares! So, these cells will exclaim with joy (in an inaminate, imaginary kind of way), "Hey, this is me!" Or, to put it more scientifically, the transfused lymphocytes will not attempt to mount an immune response against the recipient's tissues. Child 1's white cells, on the other hand, are going to see the foreign HLA antigens on the transfused white cells that are NOT shared (in other words, they will see the HLA antigens coded for by the green version of chromosome 6 in the figure), say, "Hey, this is not me!", and clear those cells from the circulation fairly rapidly. No problem, right? So, when an HLA-heterozygous donor gives blood to an immunocompetent HLA-homozygous recipient, TA-GVHD is not likely.
The second situation is just the reverse. Imagine that the donor is Child 1 this time, with Child 2 the recipient. This is illustrated below:
Let's walk through this one, too. When Child 1's blood goes into Child 2, the transfused white cells look around and see the HLA antigens that are not shared (again, the ones coded by the green colored chromosome 6 in Child 2) and say, "Hey, this is not me!", and begin to mount an immune response against Child 2's tissues. Under normal conditions, that wouldn't be a big deal, because the intact recipient white cells would just destroy the attacking cells based on HLA incompatibility (this is what happens in virtually all "normal" transfusions, as we described above). However, look at the figure again, and you will see that when the recipient's white cells look at those attacking child 1 white cells, they see only HLA antigens that are shared; in other words, they think, "this is me!" So, the normal counterattack of the recipient's white cells is eliminated, and they just sit around watching as the transfused white cells attack! This "benign neglect" is a perfect set-up for TA-GVHD, but it is TA-GVHD that can occur in completely immunocompetent people. To summarize, TA-GVHD is a danger, regardless of the recipient's immune status, when blood from an HLA-homozygous donor is transfused into an HLA-heterozygous recipient who shares one of the donor's HLA haplotypes.
I'm sorry, I know that you are exhausted from reading this incredibly long diatribe! I'm almost done. Go and grab a sandwich or something, OK? If you've made it this far, you have earned it!
— Blood Bank Guy
So, what the heck does this have to do with our question? What was our question, anyway? I'll save you from scrolling all the way back up and pull it back down here for you: "Why does blood from a donor who is related to the recipient need to be irradiated before transfusion?" The reason is that the set-up we have just described, that of the HLA-homozygous donor and the HLA-heterozygous recipient who shares an HLA haplotype with that donor, is more likely to occur in families where parents share one HLA haplotype, as we have illustrated in our imaginary family above. So, even though the vast majority of real world family member transfusions are unlikely to result in this type of interaction, we still irradiate blood from family member donors just to be safe and avoid TA-GVHD. In case you have forgotten, irraditation deactivates transfused lymphocytes and prevents them from mounting the initial "attack" on foreign HLA antigens that we outlined above.
You are a smart person, as evidenced by the fact that you are still suffering through this (either that, or you just really like torturing yourself!). You are probably saying "Joe, couldn't this happen outside of families, too?" Yep, absolutely it could! It is, however, less likely to occur outside of families, so we don't routinely irradiate all transfusions. We are also fortunate that even in the perfect scenario outlined above, TA-GVHD doesn't happen as often as it could (some studies in "genetically limited" populations have shown that).
— Blood Bank Guy
A separate question that I get asked often regarding irradiation is this: "Why does blood that is 'HLA-matched' need to be irradiated?" The answer is similar to what we have outlined above, though not identical. Remember, "HLA-matched" usually really means "HLA-as-close-as-we-could-get." So, the donor may be close enough to the recipient, HLA-wise, that the donor is not recognized as foreign while the recipient does appear foreign to the donor, leading to a possible set-up for TA-GVHD.
Back to FAQ Index.