Human blood can be typed into Type A, Type B, Type O or Type AB blood because of the existence of similar molecules embedded in the membrane of the red blood cells.  This section of the online activity explains how those blood types arise.  By the way - for testing purposes, I will use the terms antigens and antibodies (vs. agglutinogens & agglutinins).  

The Antigens (agglutinogens):    The different blood types in the ABO system arise from the existence of similar molecules on the RBC membrane (see Figure 1).   In each type (A, B, or O), the "base unit" is the same - a protein with a lipid known as ceramide  associated with it. Four sugars  extend from the ceramide into the extracellular fluid.  These sugars (in order from the ceramide) are galactose- N-acetylgalactosamine -galactose.  The last galactose also has a fucose at right angles to it (in Figure 1, the fucose is indicated by the yellow triangle).   This base unit is referred to as the "H-antigen" and is the unit present on Type O blood.  Type A and Type B blood are distinguished by the addition of a fifth sugar (Type A blood has an additional N-acetylgalactosamine on the end, while Type B blood has an galactose as the fifth sugar).  

Regarding the function of these proteins/sugars: We currently do not know for a fact what the A, B and O antigens do. Interestingly enough, the percentage of the population that expresses the different blood types is very different in different parts of the world, which has been taken to indicate some degree of selection pressure one way or another. In Caucasian populations (the US and Northern Europe), about 90% of the population is either type O or type A, while in Asian populations, the distribution is more even and only somewhat more than 50% of the population is types O or A (so there are many more people with type B blood or type AB).


Figure 1:  The ABO system of blood types results from the presence of different sugars on the extracellular end of a ceramide molecule embedded in the membrane of the RBC.   The presence and identity of the added sugar  is determined by the type of enzyme produced in the red blood cell. 


Creating these antigens:  The blood type you have is determined by the genes encoding the enzymes which build this unit.  The gene in question resides on human chromosone 9. The gene encodes an enzyme (transferase) responsible for placing a fifth sugar moeity onto the ceramide backbone. People with type A blood have a transferase that puts that last N-Acetylgalactosamine in place, while type B blood is the result of a transferase that positions the galactose there.  It appears that people with Type O blood have a single-base deletion in the gene encoding for the transferase that results in an open reading frame and the production of protein that has no transferase activity.   The latter is a recessive gene, while the genes encoding the transferases leading to type A or Type B blood are both dominant in inheritance.  Type AB blood results from the inheritance of both transferases  - since they are co-dominant, both enzymes are expressed in the cell and lead to the appearance of both the A and B antigens on the erythrocyte membranes.   

The following table lists the blood antigen present and the genotypes that can produce them:  

Phenotype (Blood type) Genotype
H antigen (Type O) OO
A antigen (Type A) AA or AO
B antigen (Type B) BB or BO
Both A & B antigens (Type AB) AB


The Antibodies (agglutinins)

We have now discussed the antigens (agglutinogens) which gave each of us our blood types.  The other half of the blood typing story is that each of us will also have antibodies (agglutinins) in our plasma.  These antibodies appear at or shortly after birth and are directed towards the antigens that are not found on our cells (that is, they are directed at the foreign molecules).

The difference in the terminal sugars for Type A and Type B antigens is sufficient for the immune system to recognize these molecules as foreign.  It is important to note that type O blood (the presence of the H-antigen) is not recognized as foreign by the immune system since all three molecules share that common base.  The following table lists the blood types (antigens on the cells) and the corresponding antibodies you would find in their plasma: 

Antigen (Blood type) Antibody in plasma
H antigen (Type O) Anti-A, Anti-B
A antigen (Type A) Anti-B
B antigen (Type B) Anti-A
A & B antigens (Type AB) none


Take, for example, the case illustrated below (Figure 2).   

Figure 2:  The red blood cell illustrated has the A antigen present on the cell membrane, indicating that this person's blood type is Type A.  That means that the B antigen is recognized as foreign - therefore antibodies directed against the B antigen are found in this person's plasma. 

As alluded to at the beginning of this section, there is some debate as to why these antibodies appear in the blood so early in life (even though the fetus probably has never been exposed to another blood type - the vast majority of antibodies appear only after an initial exposure (e.g. chicken pox)).  One theory maintains that these antibodies are genetically coded to be produced even though the body has never been exposed to that antigen before.  Another possibility is that the immune system is responding to the presence of very similar proteins on the cell membranes of the bacteria that colonize the G.I. tract.  The bacterial protein that is similar to the blood type (in this case, the A molecule) is recognized as self and therefore does not cause the production of antibodies, while the protein that is dissimilar (the B molecule) is recognized as foreign and causes antibody production.   Both of these theories have their strengths and weaknesses.  There will be no test questions that ask about the stimuli which leads to the production of antibodies directed against the ABO system. 

Test yourself:  Look at Figure 3  and determine what antibodies would be found in this person's plasma.  Click on the correct antibody (in the picture) to check yourself.  

Figure 3:  Identify which antibodies are found in the plasma of this person, then click on the choice (in the picture) that matches your answer.   


    • The ABO system of blood types results from the presence of three different molecules on the membrane of the red blood cell.  
    • The base unit for these molecules is ceramide with four sugars extending from it.  This base unit (aka the H antigen) is found on the cells of a person with Type O blood. 
    • Type A blood results when an enzyme that attaches an additional sugar (N-acetylgalactosamine) is produced in the red blood cell. 
    • Type B blood results when the enzyme produced attaches a galactose to the base unit.  
    • The enzymes that lead to the production of type A and Type B blood are co-dominant. Therefore, the presence of both genes will lead to Type AB blood.  
    • Type O blood is inherited when the person receives two copies of the truncated gene.  This leads to the presence of the H-antigen on RBC.  The H antigen does not lead to the production of antibodies against it.  
    • Your plasma contains antibodies directed against the ABO molecules you DO NOT have on your red blood cells.  If you have type O blood, you recognize both the A and the B antigens are foreign and have antibodies directed against them.  If you have type AB blood, you recognize both antigens as "self" and do not have antibodies directed against either antigen. 
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