• Different blood types have different antigenic and immune properties.
• Antibodies in the plasma of one blood type can react with antigens on the surface of the red blood cells (RBCs) of another blood type.
• If blood is transfused between people with unmatched blood types, immediate or delayed agglutination (clumping) and hemolysis (destruction) of RBCs can occur.
• Before a blood transfusion, doctors can determine whether the donor’s and recipient’s antibodies and antigens will cause a transfusion reaction.
• At least 30 common antigens and hundreds of rare antigens are present on the cell membrane surface of human blood cells.
• Each antigen can sometimes produce an antigen–antibody reaction.
• Most blood cell antigens are weak.
• These weak antigens are mainly important for studying gene inheritance and establishing parentage.
• Two antigen systems are much more likely than others to cause blood transfusion reactions.
• These are:
  • O-A-B antigen system
  • Rh antigen system

Key Concept

• Different blood types have different antigens and antibodies.
• Incompatible blood transfusion causes agglutination and hemolysis of RBCs.
• Although many blood cell antigens exist, the O-A-B and Rh antigen systems are the most important causes of blood transfusion reactions.

O-A-B BLOOD TYPES

• Two antigens, Type A and Type B, are present on the surface of the red blood cells (RBCs) in many people.
• These antigens are also called agglutinogens because they often cause RBC agglutination (clumping).
• These agglutinogens are responsible for most blood transfusion reactions.
• According to inheritance, a person may:
  • Have neither A nor B agglutinogen.
  • Have only A agglutinogen.
  • Have only B agglutinogen.
  • Have both A and B agglutinogens.
• In blood transfusion, donor and recipient blood is classified into four major O-A-B blood types.
• Table 36.1 shows these four major blood types.
• The classification depends on the presence or absence of A and B agglutinogens.
• If neither A nor B agglutinogen is present, the blood type is O.
• If only A agglutinogen is present, the blood type is A.
• If only B agglutinogen is present, the blood type is B.
• If both A and B agglutinogens are present, the blood type is AB.

Key Concept

• Type A and Type B antigens are called agglutinogens.
• The presence or absence of these agglutinogens determines the four major O-A-B blood types: O, A, B, and AB.
• These agglutinogens are the main cause of blood transfusion reactions.

Genetic Determination of the Agglutinogens

• The ABO blood group genetic locus has three alleles.
• Three alleles mean three different forms of the same gene.
• These three alleles are IA, IB, and IO.
• These alleles determine the three blood group genes.
• These alleles are commonly called A, B, and O.
• Geneticists often represent these alleles using the letter “I”.
• The letter “I” stands for immunoglobulin.
• The O allele does not produce a significant type O agglutinogen on red blood cells.
• The A allele produces strong type A agglutinogens on red blood cells.
• The B allele produces strong type B agglutinogens on red blood cells.
• The O allele is recessive to both the A and B alleles.
• The A and B alleles show co-dominance.
• Each person has two sets of chromosomes.
• Therefore, each person has one ABO allele on each chromosome.
• Since there are three different alleles, there are six possible allele combinations.
• Table 36.1 shows these six combinations.
• The six genotypes are:
  • OO
  • OA
  • OB
  • AA
  • BB
  • AB
• These allele combinations are called genotypes.
• Every person has one of these six genotypes.
• A person with genotype OO produces no agglutinogens.
• Therefore, the blood type is O.
• A person with genotype OA or AA produces type A agglutinogens.
• Therefore, the blood type is A.
• Genotypes OB and BB produce type B blood.
• Genotype AB produces type AB blood.

Key Concept

• The ABO blood group is controlled by three alleles: IA, IB, and IO.
• IO is recessive, while IA and IB are co-dominant.
• The six genotypes (OO, OA, OB, AA, BB, AB) determine the four blood types: O, A, B, and AB.

Relative Frequencies of Different Blood Types

• The frequency of blood types can vary among different populations.
• In one group of people, the approximate frequency of blood types was:
  • O: 47%
  • A: 41%
  • B: 9%
  • AB: 3%
• These percentages show that the O gene occurs more frequently than the B gene.
• They also show that the A gene occurs more frequently than the B gene.

Key Concept

• Blood type frequencies differ among populations.
• In the studied group:
  • O = 47%
  • A = 41%
  • B = 9%
  • AB = 3%
• The O and A genes are more common than the B gene.

Agglutinins

• If type A agglutinogen is not present on a person’s red blood cells (RBCs), anti-A agglutinins develop in the plasma.
• If type B agglutinogen is not present on the RBCs, anti-B agglutinins develop in the plasma.
• Table 36.1 shows the agglutinogens and agglutinins present in each blood type.
• Type O blood contains no agglutinogens.
• Type O blood contains both anti-A and anti-B agglutinins.
• Type A blood contains type A agglutinogens.
• Type A blood contains anti-B agglutinins.
• Type B blood contains type B agglutinogens.
• Type B blood contains anti-A agglutinins.
• Type AB blood contains both A and B agglutinogens.
• Type AB blood contains no agglutinins.

Key Concept

• Agglutinins are antibodies present in the plasma.
• Anti-A agglutinin develops when A agglutinogen is absent.
• Anti-B agglutinin develops when B agglutinogen is absent.
• Type O: No agglutinogens, both anti-A and anti-B agglutinins.
• Type A: A agglutinogens, anti-B agglutinins.
• Type B: B agglutinogens, anti-A agglutinins.
• Type AB: Both A and B agglutinogens, no agglutinins.

Titer of Agglutinins at Different Ages

• Immediately after birth, the amount of agglutinins in the plasma is almost zero.
• At 2 to 8 months after birth, an infant begins to produce agglutinins.
• Anti-A agglutinins are produced when type A agglutinogens are not present on the cells.
• Anti-B agglutinins are produced when type B agglutinogens are not present on the cells.
• Fig. 36.1 shows the changing titers of anti-A and anti-B agglutinins at different ages.
• The maximum agglutinin titer is usually reached at 8 to 10 years of age.
• After 8 to 10 years, the agglutinin titer gradually decreases throughout the rest of life.

Key Concept

• Agglutinins are almost absent at birth.
• Production begins at 2–8 months of age.
• Maximum titer occurs at 8–10 years of age.
• The agglutinin titer gradually declines with increasing age.

Figure 36.1: Average Titers of Anti-A and Anti-B Agglutinins at Different Ages

This graph explains how the amount (titer) of naturally occurring antibodies (agglutinins) changes throughout life.

• Red Line = Anti-A Agglutinins
• Blue Line = Anti-B Agglutinins

Step 1: Understand the Axes

X-Axis (Horizontal)

Age of person (Years)

• Starts from birth (0 years)
• Ends at 100 years
• Shows how antibody levels change as a person grows older.

Y-Axis (Vertical)

Average Titer of Agglutinins

“Titer” means:

The concentration (amount) of antibodies present in plasma.

Higher value = More antibodies

Lower value = Fewer antibodies

Step 2: Red Line (Anti-A Agglutinins)

What is Anti-A?

Anti-A antibodies attack A antigen.

They are present in:

• Blood Group B
• Blood Group O

They are NOT present in Group A or AB.

At Birth (0 years)

The red line starts almost at zero.

Meaning:

• Babies are born with almost no Anti-A antibodies.

Why?

Because the baby’s immune system is still immature.

During First Few Months

The red line rises very steeply.

Meaning:

The baby begins producing Anti-A antibodies rapidly.

Why?

Because after birth the baby is exposed to:

• Food
• Bacteria
• Environment

Some bacterial antigens resemble A antigen.

The immune system mistakenly learns to produce Anti-A antibodies.

Around 8–10 Years

The red line reaches its highest point.

This is called the Peak Titer.

Meaning:

This is the age when Anti-A antibody concentration is maximum.

The immune system is strongest during childhood.

Approximate value:

Nearly 380–390 units

After 10 Years

The red line starts going downward.

Meaning:

Anti-A antibodies gradually decrease with age.

Not because they disappear,

but because immune activity slowly declines.

Adult Age (20–50 Years)

The decrease becomes gradual.

Adults still have Anti-A antibodies,

but less than children.

Old Age (60–100 Years)

The red line continues falling.

Meaning:

Older people have much lower Anti-A antibody levels.

Reason:

Aging causes reduced antibody production.

This is called immune senescence.

Even at 90–100 years,

Anti-A antibodies are still present,

just in lower amounts.

Step 3: Blue Line (Anti-B Agglutinins)

What is Anti-B?

Anti-B antibodies attack B antigen.

They are present in:

• Blood Group A
• Blood Group O

At Birth

The blue line also starts at zero.

Meaning:

Newborn babies have almost no Anti-B antibodies.

During Infancy

The blue line rises quickly,

just like the red line,

but not as high.

Meaning:

Anti-B antibodies are produced after exposure to environmental antigens.

Peak Around 8–10 Years

The blue line reaches its highest level.

Approximate value:

Around 150–160 units

Notice:

This peak is much lower than the red line.Why is the Blue Peak Lower?

Normally,

the body produces

less Anti-B antibody than Anti-A antibody.

Therefore,

Anti-B titers are naturally lower.

This is an important physiological fact.

Adult Life

After childhood,

Anti-B antibodies slowly decrease.Old Age

The blue line continues declining.

At 90–100 years,

only a small amount remains.

Step 4: Compare Both Lines

Feature	Red Line (Anti-A)	Blue Line (Anti-B)
Antibody	Anti-A	Anti-B
Present in	Group B & O	Group A & O
At birth	Almost zero	Almost zero
Peak age	Around 8–10 years	Around 8–10 years
Maximum level	Very high (~380)	Lower (~160)
Adult level	Decreases gradually	Decreases gradually
Old age	Low but present	Low but present

Step 5: Why Do Both Lines Rise After Birth?

The baby is not born with these antibodies.

Instead,

after birth,

the immune system is exposed to:

• Intestinal bacteria
• Food proteins
• Environmental microorganisms

Many of these organisms contain molecules similar to A and B antigens.

The immune system responds by producing:

• Anti-A antibodies (if A antigen is absent)
• Anti-B antibodies (if B antigen is absent)

These are called naturally occurring ABO antibodies.

Step 6: Why Do They Fall in Old Age?

As people age:

• Bone marrow becomes less active.
• B-lymphocyte function decreases.
• Antibody production slows.
• Immune system becomes weaker.

Therefore,

both Anti-A and Anti-B titers gradually decline.

• Newborns have almost no ABO antibodies.
• ABO antibodies begin to appear at 2–8 months of age.
• Maximum antibody titer occurs around 8–10 years.
• Anti-A antibody titer is normally much higher than Anti-B titer.
• Both antibody titers gradually decrease with aging.
• Anti-A is present in Blood Groups B and O.
• Anti-B is present in Blood Groups A and O.
• Blood Group AB has neither Anti-A nor Anti-B antibodies.
• Blood Group O has both Anti-A and Anti-B antibodies.
• These antibodies are naturally acquired due to exposure to environmental and intestinal bacterial antigens after birth.

One-Minute Exam Summary

• Birth: Almost no Anti-A or Anti-B antibodies.
• 2–8 months: Antibody production begins.
• Childhood (8–10 years): Highest antibody levels.
• Red line (Anti-A): Higher than blue line throughout life.
• Blue line (Anti-B): Lower peak but follows the same pattern.
• Adulthood: Gradual decline.
• Old age: Lowest antibody titers due to decreased immune function.

Origin of Agglutinins in Plasma

• Agglutinins are gamma globulins, like most other antibodies.
• They are produced by the same bone marrow and lymph gland cells that produce antibodies against other antigens.
• Most agglutinins are IgM and IgG immunoglobulin molecules.
• People who do not have certain agglutinogens on their RBCs still produce the corresponding agglutinins.
• A possible reason is that small amounts of type A and type B antigens enter the body through:
  • Food
  • Bacteria
  • Other sources
• These substances stimulate the production of anti-A and anti-B agglutinins.
• Infusion of group A antigen into a person with non-A blood type produces a typical immune response.
• This immune response causes the formation of more anti-A agglutinins.
• Neonates have few or no agglutinins.
• This shows that agglutinin production occurs almost entirely after birth.

Key Concept

• Agglutinins are gamma globulin antibodies, mainly IgM and IgG.
• They are produced by bone marrow and lymph gland cells.
• Exposure to A and B antigens from food, bacteria, and other sources stimulates agglutinin formation.
• Agglutinins develop mainly after birth, as neonates have very few or none.

Agglutination Process in Transfusion Reactions

• When mismatched blood is transfused, anti-A or anti-B plasma agglutinins mix with RBCs that contain A or B agglutinogens, respectively.
• The RBCs agglutinate (clump together) because the agglutinins attach to the RBCs.
• IgG agglutinins have 2 binding sites.
• IgM agglutinins have 10 binding sites.
• One agglutinin can attach to two or more RBCs at the same time.
• This causes the RBCs to become linked together by the agglutinin.
• As a result, the RBCs form clumps.
• This clumping process is called agglutination.
• These RBC clumps can block small blood vessels throughout the circulatory system.
• Over the next hours to days, the agglutinated RBCs are destroyed.
• Destruction occurs because of:
  • Physical distortion of the cells
  • Attack by phagocytic white blood cells
• The RBC membranes break down and release hemoglobin into the plasma.
• This destruction of RBCs is called hemolysis.

Key Concept

• Mismatched blood transfusion causes agglutination when agglutinins bind to incompatible RBC agglutinogens.
• IgG has 2 binding sites, while IgM has 10 binding sites, allowing RBCs to clump together.
• Agglutination blocks small blood vessels.
• Hemolysis occurs when agglutinated RBCs are destroyed, releasing hemoglobin into the plasma.

Acute Hemolysis Occurs in Some Transfusion Reactions

• Sometimes, mismatched donor and recipient blood causes immediate hemolysis of RBCs in the circulating blood.
• In this situation, antibodies activate the complement system.
• The complement system forms a membrane attack complex (cytolytic complex).
• This complex inserts into the lipid bilayer of the RBC membrane.
• It creates membrane pores that are permeable to ions.
• Ions move through these pores, causing osmotic lysis of the RBCs.
• This results in immediate intravascular hemolysis.
• Immediate intravascular hemolysis is less common than agglutination followed by delayed hemolysis.
• A high antibody titer is required for immediate hemolysis to occur.
• A different type of antibody is also mainly required.
• These antibodies are mainly IgM antibodies.
• IgM antibodies that cause hemolysis are called hemolysins.

Key Concept

• In some mismatched blood transfusions, antibodies activate the complement system.
• The membrane attack complex forms pores in the RBC membrane, causing osmotic lysis.
• Immediate intravascular hemolysis is less common than agglutination with delayed hemolysis.
• High antibody levels and mainly IgM hemolysins are required for acute hemolysis.

Blood Typing

• Before a blood transfusion, the blood type of both the recipient and donor must be determined.
• This ensures that the donor and recipient blood are properly matched.
• This process is called blood typing and blood matching.
• First, the RBCs are separated from the plasma.
• The RBCs are then diluted with saline solution.
• One portion of the RBCs is mixed with anti-A agglutinin.
• Another portion is mixed with anti-B agglutinin.
• After a few minutes, the mixtures are examined under a microscope.
• If the RBCs become clumped (agglutinated), an antibody–antigen reaction has occurred.
• Table 36.2 shows the presence (+) or absence (−) of agglutination in the four blood types.
• Type O RBCs have no agglutinogens.
• Therefore, type O RBCs do not agglutinate with anti-A or anti-B agglutinins.
• Type A blood has A agglutinogens.
• Therefore, type A blood agglutinates with anti-A agglutinins.
• Type B blood has B agglutinogens.
• Therefore, type B blood agglutinates with anti-B agglutinins.
• Type AB blood has both A and B agglutinogens.
• Therefore, type AB blood agglutinates with both anti-A and anti-B agglutinins.

Key Concept

• Blood typing is performed before transfusion to ensure blood compatibility.
• RBCs are tested with anti-A and anti-B agglutinins.
• Agglutination indicates the presence of the corresponding agglutinogen.
• Type O: No agglutination with anti-A or anti-B.
• Type A: Agglutinates with anti-A.
• Type B: Agglutinates with anti-B.
• Type AB: Agglutinates with both anti-A and anti-B.