Distinguished by particular cell membrane surface antigens (protein markers) on red blood cells (RBCs), there have been over 35 different blood groups identified thus far. Although these include groups such as MNSs, Duffy, Lewis and so on, the ABO and Rh blood groups play the most significant role in blood transfusions. The frequency and stability of these blood groups in human population not only enhances our knowledge of human migration but have also been found to play a vital role in many applications of medicine including blood transfusion, transplantation, disease, and other physiological processes.
Immune System and Blood Group Compatibility
A blood transfusion involves the transfer of blood from one individual to another to restore the RBC levels and their ability to carry sufficient oxygen throughout the body. Our blood is composed of plasma (liquid portion) and formed elements, which consist of RBCs, white blood cells, and platelets. On the surface of the RBCs are antigens (substances that induce an immune response), which when bound by specific antibodies (plasma protein markers) cause agglutination or cell clumping to occur. In addition, the interactions between antibodies and antigens may lead to the destruction of RBCs, called hemolysis.
On the whole, medicine has come a long way in understanding the importance of blood group compatibility and biological mechanisms associated with blood transfusions and graft rejection. Today, matching the blood groups to prevent destruction of the donor RBCs is a relatively easy and successful procedure. As efficient as this system may be, it quickly becomes challenging due to the large numbers of blood groups and antibodies. It becomes extremely difficult when matching the various antigens that are present on tissues and organs. As a result, even after matching ABO and Rh blood groups between donor and recipient, transfusion reactions and transplantation rejection may still occur.
Whether it is a microorganism, bacterial infection, or donor blood that enters our body, our immune system has the remarkable ability to distinguish self from nonself in fighting off foreign material. This provides an explanation for unsuccessful blood transfusions of the past, where the antibodies of a recipient would combine with blood antigens from the donor, causing the transfusion reaction. The first recorded blood transfusions took place in Italy in 1628; however, the procedure was quickly banned due to the large number of deaths. It was not until the mid-19th century that human blood transfusions were again being performed in an attempt to fight against severe hemorrhages that were killing many infants after birth. This led to Leonard Lalois, a physiologist, discovering that blood cells from different species would clump together when mixed.
ABO Blood Group
The ABO blood group system was discovered in 1900 to 1902 by Karl Landsteiner and his fellow students. According to the presence or absence of antigens on the surface of RBCs, four different blood groups were determined: type A, B, AB, or O.
In the ABO system, type A blood has the A surface antigen with the ability to produce B antibodies in its blood plasma against type B antigens, which makes it compatible with type A and O. Type B has the B antigen on its surface with the ability to produce A antibodies against type A antigens, making it compatible with type B and O. Furthermore, Type AB, known as the universal acceptor, has both A and B surface antigens and cannot produce A nor B antibodies against other ABO blood antigens. Last, type O blood, which is known as the universal donor, has neither A nor B surface antigens and has the ability to produce both A and B antibodies against type A and B antigens.
Thus, if a person with type A blood were transfused into a person with type O blood, antibodies would be produced in the plasma against the A antigen on the RBC, leading to its destruction and possible death of the patient. If type O blood is transfused into an individual of type A blood, no reaction occurs between RBC antigens from the donor and antibodies of the recipient.
In the United States today, the Caucasian population has a distribution of 47% type O, 41% type A, 9% type B, and 3% type AB. The African American population has a distribution of 46% type O, 27% type A, 20% type B, and 7% type AB.
Rh Blood Group
The Rhesus or Rh blood groups were first discovered in 1940 by Landsteiner and Wiener, who found that the RBCs in the Rhesus monkey and the majority of humans would clump together when exposed to rabbit antibodies made against Rhesus RBCs. Further evidence was shown when an Rh mother showed a strong reaction against her ABO compatible, Rh+ husband during a blood transfusion. The clumping of the husband’s blood demonstrated that her body had antibodies against the Rh antigen and that it was not due to ABO incompatibility. Human blood that does not have the Rhesus antigen, 15% of the population, is Rh negative, whereas 85% of the population do possess the antigen and are Rh positive. The common types of Rh antigens, C, D, and E, are named because of their specific loci (locations) along the chromosome. Overall, there are over 45 different antigens in the Rh blood groups system, making it the most polymorphic of them all.
For antibodies to develop against the Rh antigen, an Rh- individual must be exposed to Rh+ blood via blood transfusion or pregnancy. Furthermore, with 1 in 1,000 births being diagnosed with anemia, a deficiency of RBCs, Rh blood compatibility becomes extremely important during pregnancy. During pregnancy or child birth, because the IgG antibody (one type of antibody) is capable of crossing the placenta, the RBCs from an Rh+ fetus may enter the blood of an Rh- woman. Now that this Rh- individual has become sensitized and produced anti-Rh antibodies, a subsequent blood transfusion or pregnancy of Rh+ blood would cause a reaction. There would be sufficient anti-Rh antibodies produced by the mother because she has already been sensitized, which would cause agglutination and hemolysis of fetal RBCs.
This would result in hemolytic disease of the newborn (HDN), the destruction of fetal red blood cell, causing decreased oxygen transport and jaundice due to the breakdown of hemoglobin (oxygen-carrying molecule). However, treating the mother with an anti-Rh antibody mixture (RhoGAM) within 72 hours may prevent this from occurring. This treatment is successful by preventing sensitization and allowing antibodies to bind to Rh antigens of any fetal RBCs that have entered the mother’s blood.
For almost an entire century, ABO blood typing was used in forensic laboratories, until enhanced knowledge and technology made it a procedure of the past. Looking into the genetic aspect, there are two alleles in every human that determine blood type, one from each parent. Thus, there is a total of six different possibilities of blood types: AA, AO, BB, BO, AB, and OO. However, although it is easier to distinguish between type O and type AB, it becomes impossible to distinguish types AA from AO and BB from BO. This is because the blood groups are codominant (both alleles being expressed at the same time); thus, blood typing would identify them both as type A or type B accordingly.
Population Frequencies and Historical Studies
Physical anthropologists of antiquity have agreed that distinguishing factors for humans must have the ability to remain stable while being transferred to the genes of an individual. Researcher A. E. Mourant has explained how in contrast to physical characteristics of an individual, the blood groups antigens maintain more stability in the formation process and therefore are not as easily influenced. There are exceptions to this, which include the diseases such as sickle cell anemia and thalassemia. With any complex system in nature, there are many influences that affect the frequency of a gene through generations such as mutations, natural selection, or mixing of populations. With natural selection, these influences have the ability to select for genes that would be advantageous for the individual. For example, researchers that find a higher-than-normal frequency of a particular blood group will attempt to determine possible explanations for this occurrence. If a gene undergoes mutation, the resulting effects will be determined by the selective value of the effect on the individual. If the effects bring about minimal value, the mutation will eventually die out through generations. Last, human procreation brings together the intermixing of genes, resulting in new possibilities for the next generation. Thus, these may affect specific gene frequencies throughout different populations.
One classic example of tracing migration of populations can be understood by studying the blood group frequencies of the Gypsies. Mourant describes how the Gypsies who are scattered throughout Europe are composed of approximately 20% type A, with higher type B frequencies. Researchers are able to compare different blood group frequencies along with other data of populations to try and determine where they migrated from. These findings along with other blood group studies have provided strong support for their migration from northern India.
During World War II, Professor Fleure and Mrs. Hirszfeld were the first to discover a variation in blood group frequencies between different populations. It has been primarily the research of Professor Boyd and Fleure that has provided a basis for understanding the distribution of blood groups throughout the world.
By using gene frequencies of the four blood groups, McArthur and Penrose had estimated the total population to be O 62.3%, A 21.5 %, and B 16.2%. These statistics were found to be different from present studies of Caucasian populations in the United States. A high frequency of type O has been found to exist in North Western Europe, some areas in Australia, South West Africa, and other isolated regions. The researchers made a significant finding when they discovered that most of the Native tribes of Central, South, and North America are almost entirely composed of type O. Although no strong patterns were found to exist with type A, researchers found its existence to be rare in Aboriginal populations of the world. Similarly, type B was found to be extremely rare throughout Native Americans and Australian Aborigines, and it is likely that no type B existed before the arrival of White men. In addition, type B existed in higher frequency in central Asia and northern India, while showing lower occurrences in Egypt and central Africa. During these historical studies, Fleure discovered that although frequencies varied among populations, blood groups have been shown to have a minimal impact on their survival.
So, how did humans evolve to possess different blood groups? One interesting fact that has been discovered is that certain anthropoid apes have the same A and B blood groups that are found in humans. Does this mean that the apes were the common source for human ABO blood groups? On the contrary, many Native American tribes have been found to possess almost all group O blood, with minimal type A and B. Further research has shown that the Native Americans already possessed the type A blood before the presence of White men. Researchers continue to find rare similarities that bring an additional twist to existing theories on human blood groups. For example, the blood group distributions between Greenlanders and Australians are tremendously similar. A number of examples have been found where certain “unrelated populations” have identical blood group distributions. Thus, Wyman and Boyd feel that this supports the theory that blood groups are older than the present races.
A professor of genetics, Bryan Sykes, analyzes historical blood group studies to find a common principle evident today. Through genetics and evolution, there is a greater chance of populations being related if they share similar gene frequencies than if their frequencies greatly differ.
To think that humanity has only begun over the last century to understand the importance of blood group compatibility is incredible. From blood transfusions and organ transplants to a greater understanding of diseases, medical advances have saved millions of human lives. This allows one to appreciate the miracles of modern medicine that we have today. Although the efficacy of transplantation has increased tremendously, graft rejection still occurs, and further research is essential. With the advances in science and technology along with the help of immunosuppressive therapies, various organ and tissue transplants have become common and successful procedures. With further research, new discoveries and innovative treatments will continue to enhance the future of the medical field.
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