236 Maternal Antibodies to Fetal Brain Neurons and Autism
maternal circulation [1–3]. The programmed cell death is an essential part
of embryogenesis and normal functioning of life. This is a huge subject by
itself and beyond the scope of this book. Of note, cellular death is akin to
carving a statue by a sculptor, where a chisel is used to remove the unwanted
pieces of a stone, and apoptosis is similar, where unwanted cells are removed
by a highly orchestrated system and at the end there is a “perfect offspring”.
In this process there is no antigenic residue left behind to confuse the
immune system. However, in the case of the extraordinary killing of brain
cells by harmful chemicals or sometimes in utero infection, the apoptosis
mechanism is saturated and reaches a threshold, and the cells are not com
pletely processed. This results in a larger than normal amount of neuroan
tigens that would spill out into the maternal blood circulation (if the fetal
antigens cross the placenta and reach the maternal circulation). In such a
situation, the mother’s adaptive immune system would produce antibodies
in response to those antigens. These antibodies can enter the fetal circula
tion and can damage the fetus and sometimee even kill the fetus.Are there Examples of Such an Immune Mechanism?
A prime example is a disease called “erythroblastosis fetalis”. There are two
main causes of erythroblastosis fetalis: Rh incompatibility; and ABO incom
patibility. Human red blood cells have specific chemicals that determine our
blood group: A, B, AB, and O. In addition, blood can be either Rh positive
(Rh+) or Rh negative (Rh−). If a person is type A and Rh+, then he or she is A+.
Similarly, if a person is AB−, then he or she has both A and B antigens on the
surface of the red blood cells but lacks the Rh antigen [4,5].Rh Incompatibility
Rh incompatibility occurs when an Rh− mother conceives from an Rh+ father.
The result can be an Rh+ baby. In such an event, the baby’s Rh antigens will
leak into the maternal blood circulation during the birth process and the
mother’s adaptive immune system recognizes the Rh antigen as foreign antigen,
similar to the way pathogenic viruses or bacteria are recognized by the
immune system. If the mother gets pregnant with another baby who is also
Rh+ then antibodies to the Rh antigen would enter the fetal blood circulation
and begin to destroy the fetal red blood cells. This second Rh+ fetus is in
danger of developing fetal anemia and may be stillborn. Therefore, Rh incom
patibility is not as much of a concern for the first baby but may cause fetal
anemia in subsequent Rh+ babies. Figure 8.1 illustrates this concept and the
immune mechanism that can be applied in the case of fetal antigen release
into the maternal blood [6].