Download B antigen

dr. Husnil Kadri, M.Kes
ABO BLOOD GROUP
History
1. Landsteiners discovered the ABO Blood Group
System in 1901
2. He and five co-workers began mixing each
others red blood cells and serum together and
accidentally performed the ABO groupings.
3. Main Phenotypes (A, B, AB, O)
ABO gene located on long arm of chromosome
9
History of Blood Groups and Blood
Transfusions (Cont.)
• Karl Landsteiner discovered that blood
clumping was an immunological reaction
which occurs when the receiver of a blood
transfusion has antibodies against the donor
blood cells.
•Karl Landsteiner's work made it possible to
determine blood types and thus paved the
way for blood transfusions to be carried out
safely. For this discovery he was awarded the
Nobel Prize in Physiology or Medicine in
1930.
Inheritance of ABO Groups
Allele from
the mother
Allele from
the father
Genotype of
offspring
Blood types of
offspring
A
A
AA
A
A
B
AB
AB
A
O
AO
A
B
A
AB
AB
B
B
BB
B
B
O
BO
B
O
O
OO
O
4
http://learn.genetics.utah.edu/units/basics/blood/types.cfm
Blood Transfusions
A blood transfusion is a procedure in which blood is
given to a patient through an intravenous (IV) line in one
of the blood vessels. Blood transfusions are done to
replace blood lost during surgery or a serious injury. A
transfusion also may be done if a person’s body can't make
blood properly because of an illness.
Rh +  Can receive + or Rh -  Can only receive -
Significance of ABO Group
• ABO mismatched transfusions:
– Rare
– May be life threatening
– Can be caused by technical or clerical error
– Intravascular haemolysis
– More severe in group O patients
7
The Rh(D) Antigen
• RH is the most complex system, with
over 45 antigens
• Discovered in 1940 after work on
Rhesus monkeys
• Subsequently discovered to be unrelated
to monkeys
• RH gene located on short arm of
chromosome 1
8
• Rh antigens are transmembrane proteins with
loops exposed at the surface of red blood cells.
• They appear to be used for the transport of carbon
dioxide and/or ammonia across the plasma
membrane.
• RBCs that are "Rh positive" express the antigen
designated D.
Simple Genetics of Rh(D)
• 86% of caucasians are Rh(D) pos
• The antithetical antigen d has not been
found
• The d gene is recessive:
– Dd, dD, DD, persons are Rh(D) pos
– Only dd persons are Rh(D) neg
10
Distribution of Rh(D) Types
11
Population
Rh(D) pos
Rh(D) neg
Caucasian
86%
14%
AfricanAmerican
95%
5%
Oriental
>99%
<1%
Significance of Rh(D)
• 80% of Rh(D) neg persons exposed to Rh(D)
pos blood will develop anti-D
• Anti-D can also be stimulated by pregnancy with
an Rh(D) positive baby
– Sensitisation can be prevented by the use of anti-D
immunoglobulin, antenatally and post natally
• Rh(D) neg females of childbearing potential
should never be given Rh(D) positive blood
products
12
Inheritance of ABO and Rh(D)
Mother
Group A
Father
AO
Group B
Rh(D) pos Dd
BO
Rh(D) pos Dd
Group A AO
Group B BO
Group O OO
Rh(D) pos Dd
Rh(D) pos Dd
Rh(D) neg dd
13
A person with Rh- blood can develop Rh antibodies
in the blood plasma if he or she receives blood from a
person with Rh+ blood, whose Rh antigens can trigger
the production of Rh antibodies.
•
•A person with Rh+ blood can receive blood from
a person with Rh- blood without any problems.
Why is an Rh incompatibility so dangerous
during pregnancy?
• Most anti-A or anti-B antibodies are of the IgM
class (large molecules) and these do not cross the
placenta.
•In fact, an Rh−/type O mother carrying an
Rh+/type A, B, or AB foetus is resistant to
sensitisation to the Rh antigen.
•Her anti-A and anti-B antibodies destroy any foetal
cells that enter her blood before they can elicit antiRh antibodies in her.
Rh incompatibility during pregnancy (cont.)
•This phenomenon has led to an effective
preventive measure to avoid Rh sensitisation.
•Shortly after each birth of an Rh+ baby, the
mother is given an injection of anti-Rh
antibodies (or Rhogam).
•These passively acquired antibodies destroy
any foetal cells that got into her circulation
before they can elicit an active immune
response in her.
The ABO Antigens
• Added to Proteins or Lipids in Red Cells
• Substrate Molecule is H (fucose)
• A antigen is N-acetyl-galactosamine
(GalNAc)
• B antigen is Galactose (Gal)
• A and B genes code for transferase
enzymes
17
H antigen
• The H antigen is the foundation upon
which A and B antigens are built
• A and B genes code for enzymes that add
an immunodominant sugar to the H
antigen
– Immunodominant sugars are present at the
terminal ends of the chains and confer the
ABO antigen specificity
Formation of the H antigen
RBC
Glucose
H antigen
Galactose
N-acetylglucosamine
Galactose
Fucose
A and B Antigen
• The “A” gene codes for an enzyme (transferase)
that adds N-acetylgalactosamine to the
terminal sugar of the H antigen
– N-acetylgalactosaminyltransferase
• The “B” gene codes for an enzyme that adds
D-galactose to the terminal sugar of the H
antigen
– D-galactosyltransferase
Formation of the A antigen
RBC
Glucose
Galactose
N-acetylglucosamine
Galactose
Fucose
N-acetylgalactosamine
Formation of the B antigen
RBC
Glucose
Galactose
N-acetylglucosamine
Galactose
Fucose
Galactose
Genetics
• The H antigen is found on the RBC when
you have the Hh or HH genotype, but NOT
from the hh genotype
• The A antigen is found on the RBC when
you have the Hh, HH, and A/A, A/O, or
A/B genotypes
• The B antigen is found on the RBC when
you have the Hh, HH, and B/B, B/O, or
A/B genotypes

Blood Group O people have red blood cells rich in H
antigen. Why?
Neither the A or B genes have converted the H
antigens to A or B antigens - just a whole bunch of H!
O allele at the ABO locus (amorph) It does not alter
the structure of H substance.
Donor Nucleotides & Immundominant Sugars responsible
for H, A, and B Ags specificity
Gene
Glcosyltransferase
H
L- fucosyl trnsferas
A
N acetylgalactosaminyl
transferase
B
D- galactosyl
transferase
Nucleotide
Immunodominant sugar
Antigen
Guanosine
L-fucose
H
N-acetyl-Dgalactoseamine
A
D-galactose
B
GDP-FUC
Uridine
UDPGALNAC
Uridine
UDP-GAL
ABO Antigens in Secretions
• Secretions include body fluids like
plasma, saliva, synovial fluid, etc
• Blood Group Substances are soluble
antigens (A, B, and H) that can be found in
the secretions. This is controlled by the H
and Se genes
Secretor Status
• The secretor gene consists of 2 alleles (Se
and se)
• The Se gene is responsible for the
expression of the H antigen on
glycoprotein structures located in body
secretions
• If the Se allele is inherited as SeSe or
Sese, the person is called a “secretor”
– 80% of the population are secretors
Secretors
• Secretors express soluble forms of the H
antigen in secretions that can then be
converted to A or B antigens (by the
transferases)
• Individuals who inherit the sese gene are
called “nonsecretors”
Secretions include saliva, urine, tears, bile,
amniotic fluid, breast milk, exudate, and
digestive fluids.
Lewis (Le)
• The Lewis Blood Group System is
mentioned here because it is related to
secretor status
• Lewis antigens are plasma antigens
formed by tissues and are released into
plasma where they adsorb onto the RBCs
• Consists of 2 antigens
– Lea
– Leb
ABO Subgroups
• ABO subgroups differ in the amount of antigen
present on the red blood cell membrane
– Subgroups have less antigen
• Subgroups are the result of less effective
enzymes. They are not as efficient in converting
H antigens to A or B antigens (fewer antigens
are present on the RBC)
• Subgroups of A are more common than
subgroups of B
Subgroups of A
• The 2 principle subgroups of A are: A1 and
A2
– Both react strongly with reagent anti-A
– To distinguish A1 from A2 red cells, the lectin
Dolichos biflorus is used (anti-A1)
– 80% of group A or AB individuals are
subgroup A1
– 20% are A2 and A2B
B Subgroups
• B subgroups occur less than A subgroups
• B subgroups are differentiated by the type
of reaction with anti-B, anti-A,B, and anti-H
• B3, Bx, Bm, and Bel
Other ABO conditions
• Bombay Phenotype (Oh)
• Inheritance of hh
• The h gene is an amorph and results in
little or no production of Lfucosyltransferase
• Originally found in Bombay (now
Mumbai)
• Very rare (130 worldwide)
ABO antibodies
•
•
•
•
group A serum contains anti-B
group B serum contains anti-A
group AB serum contains no antibodies
group O serum contains anti-A, anti-B, and
anti-A,B
Anti-A1
• Group O and B individuals contain anti-A
in their serum
• However, the anti-A can be separated into
different components: anti-A and anti-A1
• Anti-A1 only agglutinates the A1 antigen,
not the A2 antigen
• There is no anti-A2.
Anti-A,B
• Found in the serum of group O individuals
• Reacts with A, B, and AB cells
• Predominately IgG, with small portions
being IgM
• Anti-A,B is one antibody, it is not a mixture
of anti-A and anti-B antibodies
ABO antibodies
• IgM is the predominant antibody in Group
A and Group B individuals
– Anti-A
– Anti-B
• IgG (with some IgM) is the predominant
antibody in Group O individuals
– Anti-A,B (with some anti-A and anti-B)
ABO Antibodies
• Usually present within the first 3-6 months
of life
• Stable by ages 5-6 years
• Decline in older age
• Newborns may passively acquire maternal
antibodies (IgG crosses placenta)
Laboratory Testing:
ABO typing
ABO Blood Groups
ABO
Group
Antigen
Present
Antigen
Missing
Antibody
Present
A
A
B
anti-B
B
B
A
anti-A
O
None
A and B
anti-A, anti-B,
anti-A,B
AB
A and B
None
None
The ABO Blood Group System
Laboratory Determination of
the ABO System
Serology: This is a direct detection of the ABO
antigens. It is the main method used in blood
transfusion centres and hospital blood banks.
This form of testing involves two components:
a) Antibodies that are specific at detecting a
particular ABO antigen on RBCs.
b) Cells that are of a known ABO group that
are agglutinated by the naturally occurring
antibodies in the person's serum.
• Illustration of the forward and reverse
grouping reaction patterns of the ABO
groups using a blood group tile
http://www.bh.rmit.edu.au/mls/subjects/abo/resources/genetics1.htm
RESOURCES
• Aldahr MHS. ABO Blood Group. Faculty of Applied
Medical Sciences Blood Bank Medical Tecnology.
download 2011
• Giacobbe. ABO & Rh(D) Blood Groups. Anatomy &
Physiology. Unit 9 – Circulatory System.download 2011
• Musani MI. Blood groups and Rhesus factor. Download
2011
• Trimpe T. Blood Basics. Forensic Science.2006
• Wilkins RN. ABO Blood Group System. University of
Mississippi Medical Center. Download 2011.