Surely a mother’s immune system cannot attack her own, unborn child. A child is part of its mother, it shares her nutrients, her blood supply, her oxygen. How could it be possible?

figure 1. Pregnancy

Actually, each child is genetically distinct from their mother. While a baby does share 50% of its genome with the mother, there is another 50% which is different. This means a baby could have a different blood type as well as many other critical proteins and molecules. Left unchecked and unguarded a child could be considered a pathogen (disease causing foreign organism) by the immune system. The mother would be at war with her baby, attacking and rejecting it, much like a failed organ transplant.

Fortunately, this does not occur. There are many mechanisms that down-regulate and override this reaction. This includes the physical barrier to the mother’s T cells (white blood cells which recognise any foreign organisms) and immunosuppressive enzymes that dampen the immune response, similar to taking immunosuppressive drugs during organ transplantation. Examples include α-fetal protein and IDO.

What is Resus disease?

Under particular circumstances, the protection of an unborn baby against its mother’s immune system can be overcome. One of these instances is rhesus disease.

It is caused by the rhesus D antibody (RhD). If, during a pregnancy the baby is RhD+ (has the rhesus D antigen) and the mother is RhD- (does not have the rhesus D antigen), then some of the RhD+ cells will leak into the mother’s circulation at birth. The mother, recognising a foreign protein within her blood, will mount an immune response and produce antibodies against the RhD+ antigen.

Luckily for this first baby, it has already been born and these RhD+ antibodies cannot affect it. The problem arises when the mother has a second baby which is also RhD+. During a second pregnancy, some of the RhD+ antibodies are able to cross from the mother’s blood to the child’s. The RhD+ antibodies will begin to destroy the RhD+ cells within the baby. A summary of the mechanisms of rhesus disease is shown in figure 2.

figure 2. Summary of Rhesus disease

RhD is found on red blood cells, meaning the child’s red blood cells get killed by the mother’s immune system causing haemolytic disease of the newborn, as well as jaundice. This can be a potentially life threatening condition for the newborn baby.

How is Rhesus disease treated?

In many cases the rhesus reaction is mild and the newborn baby is simply monitored. However, there are instances where treatment to either the newborn or unborn baby is required. More detail of the treatment processes can be found here.

The rhesus reaction can be prevented completely by giving the mother specific antibodies against the rhesus protein in repeated injections. This crosslinks with the receptor on B cells that detects the RhD protein preventing its activation and production antibodies when encountering the RhD from the unborn child. However, this must be done before the mother is exposed to any RhD antigen to begin with, so must be administered during the first pregnancy.

This highlights the imperfections of the immune system. While it is superb at dealing with many pathogens encountered in every day life, it is by no means infallible. There are many ways that it can be tricked, confused and even overcome, with rhesus disease being just one of these examples. It is these imperfections that make medicine, in my view, so important.

References:
Immune tolerance in pregnancy
Rhesus disease
Haemolytic disease of the newborn
Antigens