Animated Blood Types

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  Rh Blood Factor Explanation
  Determining A-B-O Blood Types
 Blood Agglutination By Antibodies
 A-B-O Donor-Recipient Compatibility

Add a drop of anti-A antibodies (left) to blood drop A
Add drop of anti-B antibodies (right) to blood drop B


See If Drop A and Drop B Are Clumped By Antibodies
[Phenotype Percentages Based On U.S. Population]

Type O (45%): No clumping in blood drops A or B

Type A (42%): Clumping in blood drop A with anti-A antibodies

Type B (10%): Clumping in blood drop B with anti-B antibodies

Type AB (3%): Clumping in both blood drops A and B

Note: The Rh positive and Rh negative blood factors can be determined in a similar
way.  A drop of anti-Rh (anti-D) serum is added to the drop of blood and the slide is
placed on a warming box to hasten the agglutination reaction. If clumping occurs the
blood is Rh positive.  If no clumping occurs the blood is Rh negative.

Simplified Explanation For The Rh Blood Factor


Percentages Of Blood Genotypes In Hypothetical Population
There Are 4 Phenotype Percentages Including: 32% Type A (Red),
15% Type B (Green), 4% Type AB (Blue) and 49% Type O (Brown)

Alleles
0.2   A
0.1   B
0.7   O
0.2   A
AA    4%
AB    2%
AO    14%
0.1   B
AB    2%
BB    1%
BO    7%
0.7   O
AO    14%
BO    7%
OO    49%

6 Genotypes In Above Table Appear In The Trinomial Expansion (A + B + O)2 =
A2 (4%) + 2AB (4%) + B2 (1%) + 2AO (28%) +2BO (14%) + O2 (49%)

Since the A, B and O alleles are located on one pair of loci on homologous chromosome pair number one, there are a total of six genotypes: AA, AO, BB, BO, AB, and OO. If you include two variations of A (A1 and A2), there are a ten genotypes: A1A1, A1A2, A2A2, A1O, A2O, BB, BO, A1B, A2B and OO.


Models For Blood Agglutination By Antibodies

A red blood cell (RBC) with three different antigens on the surface of its membrane. The antigens are glycoproteins with unique molecular shapes. They have molecular weights of 200,000 to 300,000.


Three different types of blood antibodies that circulate in the plasma. Each antibody has two combining sites where it attaches to the complimentary antigen on the surface of a red blood cell (RBC) membrane. Anti-A and Anti-B antibodies are glycoproteins with a molecular weight of about 900,000. Anti-Rh antibodies are smaller glycoproteins with a molecular weight of about 150,000. The latter are "immune-type" (IgG) antibodies and readily pass through placental capillary membranes.


A red blood cell (RBC) containing three different antigens on the surface of its membrane. Each antigen has the complimentary antibody attached to it. The antigens and antibodies are large glycoproteins with unique molecular shapes.


Red blood cells (RBCs): Type A Positive (left) and type A Negative (right). Both types have the A antigen, but only the A Positive (left) has the Rh antigen.


Red blood cells (RBCs): Type B Positive (left) and type B Negative (right). Both types have the B antigen, but only the B Positive (left) has the Rh antigen.


Red blood cells (RBCs): Type AB Positive (left) and type AB Negative (right). Both types have A and B antigens, but only the AB Positive (left) has the Rh antigen.


Red blood cells (RBCs): Type O Positive (left) and type O Negative (right). Both types are without A and B antigens, but the O Positive (left) has the Rh antigen. Type O Negative (right) has none of the antigens (A, B or Rh) on its membrane.


Agglutination (clumping) of type A red blood cells (RBCs) by anti-A antibodies. The antibodies have two combining sites and are able to attach to the A antigens on adjacent RBCs, thus causing the RBCs to bond together. Blood clotting is an entirely different biochemical mechanism involving blood platelets (thrombocytes) and the clotting protein prothrombin which is converted into thrombin. The thrombin acts like an enzyme, catalyzing the conversion of fibrinogen protein into fibrin. The actual blood clot is composed of fibrin threads that wind around RBCs and platelets.

How Coumarin Inhibits The Clotting Process


Chart Of A-B-O Blood Donor & Recipient Compatibility

RECIPIENT
D
O
N
O
R
Alleles &
Antibodies
  O
anti-A
anti-B
  A
anti-B
  B
anti-A
  AB
None
O
None
None
None
None
A
Clump
None
Clump
None
B
Clump
Clump
None
None
AB
Clump
Clump
Clump
None

Chart of A-B-O Blood Donor-Recipient Compatibility. Serious problems may arise when the antibodies of the recipient clump the blood cells of the donor. [The reverse scenario is not as serious because the antibodies of the donor are diluted by the recipient's blood volume.] Clumping of the donor's blood is indicated by the word "Clump" in the red squares. No clumping of the donor's blood is indicated by the word "None" in the green squares. None also denotes the lack of anti-A or anti-B antibodies in the type O recipient. It is clear from this chart that the "universal donor" is type O, while the "universal recipient" is type AB. If you include the Rh factor, then the universal donor becomes O Negative while the universal recipient becomes AB Positive.


Simplified Explanation For Rh Blood Factor

Rh Neg    
Blood    

Add a drop of anti-Rh antibodies (anti-D serum) to a drop of blood
on a slide labeled Rh.  The Rh negative blood (shown above) will
not clump, while the Rh positive blood (below) will show clumping:

Rh Pos    
Blood    


Placing the Rh slide on a warming box will hasten the agglutination reaction. Backlighting will also make it easier to see the clusters of agglutinated red blood cells that appear like minute grains of sand in the blood. Rocking the slide back and forth also makes it easier to see the grainy texture of the agglutinated blood.

An Rh Blood Typing (Warming) Box.

Remember that the anti-Rh serum will only agglutinate the positive D factor. There are technically three positive genes called C, D and E. The negative alleles for these three genes are usually denoted by small case c, d and e. This is an example of multiple gene (polygenic) inheritance which is explained in more detail at the following URL:

Multiple Gene Inheritance In The Rh Factor

Although it is much more complicated, the Rh blood factor can be explained by a pair of alleles on homologous chromosome pair #1. The dominant Rh positive gene (+) produces the Rh antigen, a glycoprotein constituent of the RBC membrane (see above Rh positive RBC illustration). Like the type O gene, the recessive Rh negative gene (-) does not produce an antigen. The following table summarizes Rh inheritance in humans:

Blood Phenotype
Blood Genotype
Antigen on
RBC Membrane
Immune (IgG)
Antibodies
Rh Positive
(85% of U.S.)
+ +  or  +  -
Rh antigen
None
Rh Negative
(15% of U.S.)
- -
No antigen
May Produce
anti-Rh

If Rh positive blood is accidentally given to an Rh negative recipient, the recipient will begin producing anti-Rh antibodies. Because of the time factor involved in building up a concentration (titre) of antibodies, the first transfusion may not cause any major problems; however, a subsequent transfusion of Rh positive blood could be very serious because the recipient will clump all of the incoming blood cells. The donor-recipient scenario with Rh blood types is summarized in the following table:

Donor
Recipient
Anti-Rh Antibodies
  in Recipient's Blood  
Rh Positive
   Rh Negative   
Will Produce
anti-Rh Antibodies
   Rh Negative   
Rh Positive
Will Not Produce
anti-Rh Antibodies

Since Rh negative people may produce anti-Rh antibodies, Rh positive blood should not be given to an Rh negative recipient. Based upon the above table, Rh positive recipients can theoretically receive positive or negative blood, and Rh negative donors can theoretically give to Rh positive and Rh negative recipients. Therefore, the "universal donor" is O Negative, while the "universal recipient" is AB Positive.

Anti-Rh (immune-type) antibodies can readily pass through the placental capillary membranes. A serious potential problem called maternal-fetal blood incompatibility or Rh Disease could occur with a pregnant Rh negative mother who carries an Rh positive fetus. Leakage of fetal red blood cells (RBCs) into the mother's system through minute lesions in the placenta may cause her to produce anti-Rh antibodies. This could occur during the latter months of pregnancy or when the baby is delivered. Because of the time interval involved in producing a concentration (titre) of antibodies, the first Rh positive child may not be adversely affected. However, a subsequent Rh positive child may be at risk because the mother's anti-Rh can pass through the placenta, thus entering the fetal circulatory system and clumping fetal RBCs.

The medical term for this maternal-fetal condition is "erythroblastosis fetalis" because of the presence of nucleated, immature RBCs called erythrobasts in the fetal circulatory system. The fetus bone marrow releases immature erythroblasts because of the destruction of mature RBCs (erythrocytes) by the mother's anti-Rh antibodies. RhoGamŪ, a serum containing anti-Rh antibodies, is now given to Rh negative woman within 72 hours after giving birth to their Rh positive baby. The RhoGamŪ enters the mother's circulatory system and destroys any residual fetal positive RBCs that may be present in her system. This prevents her from producing anti-Rh antibodies. RhoGamŪ must be given after each Rh positive baby. In this scenario of erythroblastosis fetalis, the fetus must be Rh positive, the mother Rh negative and the father Rh positive. You can easily determine the exact genotype of the mother and fetus, but the father's genotype could be homozygous or heterozygous Rh positive. Rh incompatibility is summarized in the following table:

Rh Pos Father
+  +
 or  -
X
Rh Neg Mother
-  -
1st Rh Pos Child
-
Rh positive RBCs from the fetus enter the mother's circulatory system.
After several days, the mother begins to produce anti-Rh antibodies.

2nd Rh Pos Child
-
Anti-Rh antibodies from mother pass through placenta and enter fetal
circulatory system. The antibodies begin clumping fetal positive RBCs.

There are also reported cases of maternal-fetal blood incompatibility with the A-B-O blood groups; however, the Rh factor appears to be much more common. The larger anti-A and anti-B antibodies (IgM type) with molecular weights of 950,000, apparently don't penetrate the placental membranes as readily. In the case of A-B-O blood incompatibility, the anti-A and anti-B antibodies of a type O mother may enter the circulatory system of a Type A or Type B fetus, thus causing agglutination of the fetal RBCs. If the fetal blood cells just happened to be Rh positive and entered the mother's circulatory system, they would be destroyed by the mother's anti-A or anti-B antibodies before her system began to produce anti-Rh immune-type (IgG) antibodies. In this latter case, the anti-A or anti-B antibodies would actually serve as a natural immunity to Rh maternal-fetal blood incompatibility.

Like most topics in biology, the true life explanation is a lot more complicated. Rh inheritance is no exception. It actually involves three different pairs of genes at three different loci on homologous chromosome pair #1. The gene pairs are C & c, D & d and E & e. The terms "positive" and "negative" essentially refer to the D factor, so homozygous DD and heterozygous Dd are positive, while homozygous recessive dd is negative. For a more in depth explanation of this interesting example of polygenic inheritance, please refer to the following hyperlink:

Rh Factor: Another Example Of Polygenic Inheritance

Rh Factor: Another interesting example of polygenic inheritance is the Rh factor. Unlike the A-B-O blood types where all the alleles occur on one pair of loci on chromosome pair #9, the Rh factor involves three different pairs of alleles located on three different loci on chromosome pair #1. In the following diagram, 3 pairs of Rh alleles (C & c, D & d, E & e) occur at 3 different loci on homologous chromosome pair #1. Possible genotypes will have one C or c, one D or d, and one E or e from each chromosome. For example: CDE/cde; CdE/cDe; cde/cde; CDe/CdE; etc.

In order to determine how many different genotypes are possible, you must first determine how many different gametes are possible for each parent, then match all the gametes in a genetic checkerboard (See the following Table 3). Although the three pairs of genes are linked to one homologous pair of chromosomes, there are a total of eight different possible gametes for each parent: CDE, CDe, CdE, Cde, cDE, cDe, cdE, and cde. This number of gametes is based on all the total possible ways these genes can be inherited on each chromosome of homologous pair #1. [It is not based on the random assortment of these genes during meiosis in the parents because all three genes are closely linked together on the same chromosome; therefore, all three genes tend to appear together in the same two gametes: CDE and cde.] The possible different genotypes are shown in the following Table 3:

Gametes
 CDE 
 CDe 
 CdE 
 Cde 
 cDE 
 cDe 
 cdE 
 cde 
CDE
CDE/
CDE
CDE/
CDe
CDE/
CdE
CDE/
Cde
CDE/
cDE
CDE/
cDe
CDE/
cdE
CDE/
cde
CDe
CDe/
CDE
CDe/
CDe
CDe/
CdE
CDe/
Cde
CDe/
cDE
CDe/
cDe
CDe/
cdE
CDe/
cde
CdE
CdE/
CDE
CdE/
CDe
CdE/
CdE
CdE/
Cde
CdE/
cDE
CdE/
cDe
CdE/
cdE
CdE/
cde
Cde
Cde/
CDE
Cde/
CDe
Cde/
CdE
Cde/
Cde
Cde/
cDE
Cde/
cDe
Cde/
cdE
Cde/
cde
cDE
cDE/
CDE
cDE/
CDe
cDE/
CdE
cDE/
Cde
cDE/
cDE
cDE/
cDe
cDE/
cdE
cDE/
cde
cDe
cDe/
CDE
cDe/
CDe
cDe/
CdE
cDe/
Cde
cDe/
cDE
cDe/
cDe
cDe/
cdE
cDe/
cde
cdE
cdE/
CDE
cdE/
CDe
cdE/
CdE
cdE/
Cde
cdE/
cDE
cdE/
cDe
cdE/
cdE
cdE/
cde
cde
cde/
CDE
cde/
CDe
cde/
CdE
cde/
Cde
cde/
cDE
cde/
cDe
cde/
cdE
cde/
cde

Polygenic inheritance in the Rh blood factor. Every genotypic combination with DD or Dd is classified as Rh Positive (red). This is about 85% of the U.S. population because the D gene is more common than the C and E genes. Every genotypic combination with dd is classified as Rh Negative (blue). Since the ratio of C and E genes is much less than D genes, approximately 15% of the U.S. population are Rh negative (dd). Consolidating the duplicates, a total of 10 genotypes are homozygous recessive for the d allele (dd); however, nine of these genotypes are actually positive for the C and E factors: Cde/cde (0.46%), Cde/Cde (0.0036%), cdE/cde (0.38%), cdE/cdE (0.0025%), Cde/cdE (0.006%), CdE/cde (0.008%), CdE/Cde (0.0001%), CdE/cdE (0.0001%), and CdE/CdE (0.00001%). Therefore, only about 0.86% of the U.S. population are positive for C and E. Expressed as a decimal, this is 0.0086 or 8.6 out of 1000. This is why Rh incompatibility involving the C and E genes is rare in the U.S. population.

Other Examples Of Polygenic Inheritance

Antigen
Immune Antibodies (In Blood Plasma)
(RBC Membrane)
    anti-C    
anti--D
    anti-E    
C (RhC)
------
------
------
D (RhD)
------
RhoGAM & Biology TypingSerum
------
E (RhE)
------
------
------

Rh antibodies primarily utilized in immunoglobulin serums.

More than 98% of all cases of hemolytic disease of the newborn (maternal-fetal blood incompatibility) are caused by the D antigen, also referred to as RhD and Rh Positive (+). This is why RhoGam and standard blood typing kits for general biology labs only contain anti-RhD (anti-D) antibodies. Anti-C and anti-E antibodies against the C and E antigens can be associated with maternal-fetal blood incompatibility, but this is uncommon and only occurs in a small percentage of non-RhD cases. Apparently immune globulins (such as RhoGam) are not available to prevent these rare cases. According to Dr. Kenneth J. Moise, Jr., Director of the Division of Maternal-Fetal Medicine at University of North Carolina Medical School at Chapel Hill, more than 43 other RBC antigens have been implicated in the non RhD cases. Especially problematic are the Kell (K1), c, Duffy (Fya) and Kidd (Jka and Jkb) antigens. A recent study from a tertiary referral center in New York found 550 cases of antibodies associated with hemolytic disease of the newborn in 37,506 blood samples taken from women of reproductive age (1.1% incidence). Anti-D occurred in 25% of the samples, anti-Kell in 28%, anti-c in 7%, anti-Duffy in 7%, anti-Kidd in 2%, anti-E in 18%, anti-C in 6%, anti-MNS in 6%, and anti-Lutheran in 2%. The following link contains a summary of Rh maternal-fetal blood incompatibility from the UNC Department of Obstetrics and Gynecology:

Information About Maternal-Fetal Rh Disease


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