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Blood Type: Antigens, Antibodies and Transfusions

Blood transfusions in humans were risky procedures until the discovery of the major human blood groups by Karl Landsteiner, an Austrian biologist and physician, in 1900. Until that point, physicians did not understand why death sometimes followed blood transfusions when a donor’s blood infused into the patient was incompatible with the patient’s own blood. We now know that blood groups are determined by the presence or absence of specific marker molecules on the plasma membranes of erythrocytes. With their discovery, it became possible for the first time to match patient-donor blood types and prevent transfusion reactions and deaths.



  • Blood type is determined by which antigens present on red blood cells.
  • Antigens are macromolecules (usually proteins) that can elicit an immune response and help the body determine ‘self’ vs. ‘foreign’.
  • Antibodies recognize antigens and target them for degradation.
  • A person will never have an antibody that recognizing the antigen on their own red blood cells.


What are Antigens?

An antigen is a foreign or “non-self” macromolecule (typically a protein) that reacts with cells of the immune system. However, not all antigens will provoke a response. For example, each of us produce a large number of self-antigens. Each of us has a unique set of self-antigens that do not trigger an immune response within ourselves. The absence of this immune response very important and highly regulated,  it prevents scenarios where the immune cells begin to attack host cells. In the presence of foreign atnigens, proteins called antibodies attach to the antigens on the plasma membrane of the cell containing the antigen.

Antigens and ABO Blood Types

Like other cells, our red blood cells may or may not have self-antigens present on their cell membrane. The ABO blood typing is a naming scheme that states the presence or absence of just two antigens: antigen A and antigen B. The antigens that are present on the surface of our red blood cells determine our blood type. If we looking at the table below, we’ll see that:

      • Blood type A has A-antigens
      • Blood type B has B-antigens
      • Blood type AB has both A-antigens and B antigens
      • Blood type O has neither antigen.


Table showing the antigens present in each blood type.
Adapted From: OpenStaxLicense: CC BY 4.0
Red blood cell with antigens
Author: Biomed Guide | Adapted From: DBCLS 

What are Antibodies?

(aka immunoglobulins) are proteins produced and secreted by differentiated B-lymphocytes called plasma cell. They mediate the humoral immune response and are necesassary for the determination of self versus foriegn antigens. Antibodies have an interesting Y-shaped structure withat least two binding sites for one specific antigen. The areas where the antigen is recognized on the antibody are variable domains. Importantly, antibodies mark pathogens for destruction by phagocytic cells, such as macrophages or neutrophils. Because phagocytic cells are highly attracted to molecules complexed with antibodies, cells or antigens that are tagged with antibodies will eventually be engulfed and destroyed.

Antibodies and ABO Blood Types

Normally the body must be exposed to a foreign antigen before an antibody can be produced. This is not the case for the ABO blood group. Individuals with type A blood—without any prior exposure to incompatible blood—have preformed antibodies to the B antigen circulating in their blood plasma. These antibodies, referred to as anti-B antibodies, will cause agglutination and hemolysis if they ever encounter erythrocytes with B antigens. Reviewing thelook at the table below:

      • → Blood type A has Anti-B antibodies circulating in their blood.
      • Blood type B has Anti-A antibodies circulating in their blood.
      • Blood type AB has neither Anti-A antibodies, nor Anti-B antibodies circulating in their blood.
      • Blood type O has both Anti-A and Anti-B antibodies circulating in their blood

Similarly, an individual with type B blood has pre-formed anti-A antibodies. Individuals with type AB blood, which has both antigens, do not have preformed antibodies to either of these. People with type O blood lack antigens A and B on their erythrocytes, but both anti-A and anti-B antibodies circulate in their blood plasma.

Adapted From: OpenStaxLicense: CC BY 4.0
Author: NIH Human Genome Research Institue | Source:


  • → Blood Type A has A-antigens
  • → Antibodies locate antigens and target them for degradation via phagocytes. 

If blood type A had Anti-A antibodies, those antibodies would attach that individuals own blood cells! For this reason, you will have the antibodies that only recognize antigens that are not already on your blood cells.

Blood Transfusions

Following an infusion of incompatible blood, erythrocytes with foreign antigens appear in the bloodstream and trigger an immune response. Proteins called antibodies would then attach to the antigens on the plasma membranes of the infused erythrocytes and cause them to adhere to one another. Because the arms of the Y-shaped antibodies attach randomly to more than one nonself erythrocyte surface, they form clumps of erythrocytes. This process is called agglutination.

The clumps of erythrocytes block small blood vessels throughout the body, depriving tissues of oxygen and nutrients.As the erythrocyte clumps are degraded, in a process called hemolysis, their hemoglobin is released into the bloodstream. This hemoglobin travels to the kidneys, which are responsible for filtration of the blood. However, the load of hemoglobin released can easily overwhelm the kidney’s capacity to clear it, and the patient can quickly develop kidney failure.

More than 50 antigens have been identified on erythrocyte membranes, but the most significant in terms of their potential harm to patients are classified in two groups: the ABO blood group and the Rh blood group

Rh Factor

The Rh blood group is classified by the presence or absence of another erythrocyte antigen (Rh).  Although dozens of Rh antigens have been identified, only one, designated D, is clinically important. Those who have the Rh D antigen present on their erythrocytes are described as Rh positive (Rh+) and those who lack it are Rh negative (Rh).  About 85% of Americans are Rh+.

The Rh group is distinct from the ABO group. Any individual, no matter their ABO blood type, may have or lack this Rh antigen. When identifying a patient’s blood type, the Rh group is designated by adding the word positive or negative to the ABO type. For example, A positive (A+) means ABO group A blood with the Rh antigen present, and AB negative (AB) means ABO group AB blood without the Rh antigen.

Who Can Donate to Whom?

It’s important to note, when an individual receives a blood transfusion it’s typically is a specific component of blood. For example, someone might receive blood cells, platelets or plasma. For the purposes of understanding who can donate to whom, we’re going going to consider:

        1. What are the antigens on the red blood cell being donated?
        2. What are the antibodies that are present in the individual receiving the blood? 

These considerations are important. Take a look at what can happen from complications related to an incompatible transfusion. The table below shows which blood types can receive which blood cells, but let’s go through an example (on the right).

Blood transfusion table showing which blood types can donate to which blood types
Title: Blood Transfusion Chart | Author: BiomedGuide | License: CC BY-SA 4.0 

Notice a Pattern?

If you look at the table, you might have noticed something special about O and AB+. On the donor’s side, O can donate to every blood type. For this reason, Ois called the universal donor and happens to be a very useful blood type for blood transfusions. On the receiving side, AB+ can accept blood from any blood type and is called the universal recipient.

Link to Learning

Rh factor was first discovered in rhesus macaques, which are commonly used in research because of similarities that they share with humans.

Transfusion Example

  • Blood Type: B+
  • Antigens: antigen B; antigen D
  • Antibody: Anti-A

Considering this information, if you have blood type B+ and are receiving a blood tranfusion, you want to make sure the antibodies in your body don’t attack the blood cells you’re receiving from the transfusion. Therefore, you can’t receiving blood cells that have antigen-A on them. Taking a look at the chart, which blood types can you receive blood from? Do you know why?

  • Ois missing antigens A, B, and D
  • AB+ is missing Anti-A, Anti-B and Anti-D antibodies

Blood Type Practice Questions

Antigens and Blood Type 

Antibodies and Blood Type 

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