Chimeras and Autoimmunity
Written by Vicky Diep
Edited by Justin Gambill
Jan 23rd 2022
Edited by Justin Gambill
Jan 23rd 2022
In 1865, Gregor Mendel, an abbot who is known today as the “father of genetics,” published his findings on the mechanisms of inheritance. However, it was not until after his death that his ideas gained more traction within the scientific community. Today, Mendel's laws of segregation and independent assortment are an essential component of any genetics curriculum. Thanks to him, we know that every individual receives half of their genes from each parent, and the combination of genes we receive is unique due to the way that the chromosomes in our parents’ reproductive cells independently become allocated to egg and sperm cells that would later combine during fertilization. All of the cells in our body arise as mitotic copies of this original fertilized egg cell. These principles imply two fundamental things: (1) all of the cells in our bodies contain exactly the same genes, so we would expect a heart cell and a skin cell from the same person to have the same genetic makeup, despite both cells having unique functions and appearances; and (2) half of the genes in a person's cell would match with their mother's, while the other half would match up with their father's. These two basic principles form the foundation of DNA testing and paternity tests.
Nice and clear, right? However, all rules have exceptions. The exception to these rules are special organisms known as genetic chimeras, named after a mythological creature that is said to have the body of a lion, the tail of a snake, and the head of a goat. Similar to how this mythological creature of Greek lore contains body parts of different animals, genetic chimeras have cells that contain different genes (Yunis et al, 2007). If you took two different cells from the body of a chimera and compared them, you wouldn't know that they belong to the same person! Besides being a cause of confusion in paternity and maternity tests, chimeras are an interesting topic of research due to the implications of having two different cell genotypes in one body; for example, people who receive blood transfusions or organ transplants from other people are considered "temporal chimeras” because of the presence of allogeneic cells, which may be problematic if the body recognizes and reject these cells as foreign entities (Yunis et al, 2007). So how do the cells of chimeras make this distinction and avoid attacking their compatriots who differ in genetic makeup?
For organ transplants, a set of proteins called the major histocompatibility complex (MHC) are usually the proteins that are targeted by immune cells. Because of this, MHC matching is crucial to prevent the organ acceptor’s immune cells from attacking newly implanted donor cells because immune cells are trained to ignore self-MHCs and to recognize MHCs that differ from their own. Thus, immune cells who fail this “training” are destroyed. This is the basis of central tolerance in immunology, and failure to recognize self-MHC underlies autoimmune disease. Studies of chimeric mice suggest that chimeras have tolerance to their own cells due to blocking factors and a reliance on peripheral tolerance mechanisms that maintain T cell unresponsiveness (Yunis et al, 2007). Therefore, genetic chimeras are interesting subjects of research that can provide insight on autoimmune diseases.
Works Cited
Yunis, E. J., Zuniga, J., Romero, V., & Yunis, E. J. (2007). Chimerism and tetragametic chimerism in humans: Implications in autoimmunity, allorecognition and tolerance. Immunologic Research, 38(1-3), 213–236. https://doi.org/10.1007/s12026-007-0013-3