Structural Biochemistry/Carbohydrates/Blood Type

Definition of Blood

- A type of complicated and living tissue which holds numerous proteins and cell types.

- Blood is important in our bodies due to its functions: defend, regulate, and transport. It is also known as fluid tissue present in blood vessels

Structure

Human blood groups depends on the functioning of glycosyltransferases, enzymes that catalyze the formation of glycosidic bond between the Structure and function of the human blood. Specific oligosaccharide antigens attach to the proteins and lipids on the surface of erythrocytes. Those attached to proteins have a serine or threonine residue or ceramide lipid intermediate. The most basic oligosaccharide attached is called the O antigen (also referred to as the H antigen). This O antigen is the base oligosaccharide found in all three blood types AB, A, and B. The O antigen is of the form (—Lipid—Glucose—Galactose—N-acetylglucosamine—Galactose—Fucose). Blood type O only has the O antigen attached to the red blood cells. Blood type A is formed through the addition of the A antigen, which has N-acetylgalactosamine (GalNAc) glycosidically bonded to the O antigen. Similarly for blood type B, the B antigen has an additional galactose forming a glycosidic bond to the O antigen. In both the A and B blood types, the new antigen forms an α-1,3 linkage to the outermost galactose component of the O antigen through the help of glycosyltransferases. GalNAc transferase adds the extra N-acetylgalactosamine for the A antigen while Gal transferase adds the extra galactose for the B antigen. Genes in a person’s DNA code for the specific glycosyltransferases to allow for the addition of antigens A and/or B to the O antigen. If a person’s genes do not allow for the coding of type A or B transferase, then that person will have type O blood. The genes that code for GalNAc and Gal transferases are exact, but for three amino acids. This strong similarity between the two enzymes shows they are related through divergent evolution.

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Functionality

The importance of glycosyltransferases is most prominent when a person needs a blood transfusion. Type O blood can be given to anyone because everyone has the ability to recognize the O antigen. However, a person with type A or type O blood cannot recognize the B antigen while another with type B or O blood cannot recognize the A antigen. Antibodies against the B and A antigens are also present in the serum of one’s blood for those who lack the B and A antigens, respectively. Therefore, if a person were transfused with the wrong type of blood, one’s immune system will see the antigen as foreign, therefore attacking those transfused red blood cells. It is because of this process that people with type AB blood can accept transfusions of any blood type, since they have all three antigens already present in their bodies. It should be noted that in reality, transfusions are complicated by the Rhesus factor.

Proteins & Blood Types

• We can categorize our blood types into 4 groups: A, B, AB, & O

These four groups are considered to be the four phenotypes that one may posses. These four phenotypes can produce six different genotypes that each person can be: AA, AO, BB, BO, AB, and OO.

• On the surface of red blood cells, there are 2 types of antigen: A & B (each type has its own properties)

If a blood cell is type A, the surface of the cell contains Antigens for type A and the body will produce antibodies for type B and vice versa for type B. Type AB contains both antigens on the surface and has neither antibodies. Blood type O has no antigens and thus have both A and B antibodies in its system. In this regard, blood type O may be the universal donor and blood type AB is the universal recipient.

• We can also look at the property of Rh protein whether it's absence or presence in our blood.

- If a blood type has Rh protein, then it is positive.

- If a blood type does not have Rh protein, then it is negative.

- For example, blood type "B negative" means that the person has type B without Rh protein on the surface of the red blood cells.

The RH factor is more important if the mother is to have a second child. This is because if the mother is RH – and her first child is RH + (has present of RH protein), the mother will produce antibodies (specific immunogenic proteins) for the RH protein. This will not affect the first child since the mother will only produce this antibody after the child is born. However, if the mother is to have a second child with an RH+ trait as well, the antibodies in the mother will cross the placenta and attack the child. This is because the antibodies for the RH protein are specific proteins called memory cells that are small enough to pass the placenta. This will result in a miscarriage.

One way around this is to give the mother Rhogam after birth. This is a synthetic protein antibody that will destroy the left over fetal cells before it has a chance to interact with the mother's immune system. This inhibit protein antibody production towards the RH factor in the mother and will allow subsequent RH+ children to be born from that mother.

Mixing Different Blood Types

• Our body generates antigens or antibodies to protect us from the unfamiliar molecules. They will then recognize this difference and clash with the molecules to get rid of them.

• For blood transfusion, it is very important to make sure that both the recipient and the donor match in blood type.

- If surface molecules from the donor blood cells signals any difference than the recipient's, then the antibodies from the recipient’s blood will consider it as foreign.

- The immune response will take place if there is a difference in blood type, which results in blood clots in the vessels.

Universal Donors and Universal Recipients

• Blood type O is the universal donors due to its versatility of having no molecules on the red blood cell surfaces, which will not trigger any immune response. Therefore type O blood can be donated to any of the other four blood types earning its name.

• Blood type AB is the universal recipients due to its lack of antibodies that recognize type A or B surface molecules. AB can receive blood from any of the other four blood types earning its name as the universal receiver. AB however also tends to be the most rare blood type out of the four.

AB+ is the true universal receiver able to receive all types of blood regardless of type and Rh antigen.

However O- is only compatible with itself but able to donate to everyone.

The exception to these rules are people with the hh antigen system also called the Bombay blood type. These individuals cannot express the H antigen which is present in group O. They cannot make A antigen or B antigen since they are made from the H antigen. Therefore the people who have this blood type can donate to any other member of any blood type but can only receive blood from other Bombay blood type individuals. However this blood type is extremely rare occurring in only .0004% of the population. Therefore people with this blood type are at a great risk in finding compatible blood for a blood transfusion.

Rhesus Antigen

Not only do the different blood types have to be considered due to the existence of antigens but the rhesus blood group system is secondly important after the ABO system of blood type antigens. The most important antigen from the five main rhesus antigens is RhD since it is the most immunogenic. It is common for RhD negative people to have no anti-RhD IgG or IgM antibodies. The Rhesus antigen is usually depicted by a plus or a negative after the type of blood type. Rh positive is more prevalent than Rh negative blood types. Especially in East Asia the percentage of Rh negative people are extremely rare. Since people with Rh negative blood type cannot receive blood from Rh positive special care must be taken when receiving blood transfusions.

Testing for Rhesus Antigen

Test can be carried out to determine whether one's blood contains the Rh antigen. Since Rh factors are antigens there are corresponding antibodies that can be used to bind. Rh antibodies are commonly used to bind to such antigens in the blood. The structure of the antibody is oriented in a fashion so that there are two main chains, a heavy chain and light chain. The two heavy chains are located on the inner side of the antibody while the light chains are located on the outer. The domains are exactly the same pertaining to all antibodies except for the last domain the N terminus of both the heavy and light chain located on each side of the antibody. It is the variable domain that is different from antibody to antibody and contains differential amino acid sequences with their constituent residues that provide complementarity in the binding site to the specific substrate. If Rh antibodies are mixed with ones blood and aggregation occurs, then the person would be Rh positive, if no aggregation occurs, then the person is Rh negative. Aggregation occurs due to the antibody-substrate complex that forms when the Rh antigen locks into the binding site of the antibody.

Red Blood Cells Vs Blood Plasma

Like red blood cell compatibility recipients can receive blood plasma from the same blood type. However unlike with red blood cells the plasma has a converse compatibility. Blood type O can receive plasma from every other blood type while blood type AB can donate blood plasma to any blood type.

Blood Types Genetics

• Blood types A & B co-dominate

• Blood type O is recessive

• We can see the patterns of the possible combination of alleles versus the blood types:

AB = blood type AB

BB = blood type B

AA = blood type A

OO = blood type O

BO = blood type B

AO = blood type A

Blood type A can receive both type A and type O blood. Similarly, blood type B can receive both type B and type O blood. However, blood type AB can receive type A and type B blood, as well as, type O blood, making them the universal recipients. Blood type O is rare in that it can only receive type O blood, but can donate to any of the other three blood types, making them the universal donors.

References

Nelson, David L. Principles of Biochemistry, 4th ed. W. H. Freeman, 2004.

http://www.ncbi.nlm.nih.gov/books/bv.fcgi?indexed=google&rid=mcb.section.4816