2. Human red cells contain numerous surface structures that are recognized as antigens by
the immune system
These surface structures are called blood group antigens.
Based on the presence of antigens on red cell membrane,corresponding antibodies are
absent in the plasma of that individual.
The blood group antigens are called agglutinogens
Antibodies against them are called agglutinins as the reaction between them results in
clumping or agglutination of red cells.
There are more than 30 known blood group systems in our blood containing about 400
antigens (Table 16.1).
Many of them have cold antibodies that do not react at body temperature. Therefore,
only few of them are immunologically active.
ABO and Rh group systems that are most important for blood transfusion.
Other major blood group systems are MNS, Lewis, Duffy, Kell, P and Lutheran systems.
3.
4. Antigen: Proteins, Glycoproteins, or Lipids.
Substances which induce formation of corresponding
antibodies when introduced into the body, with which it
reacts specifically.
Self antigens and Non-self antigens.
Antibodies: Proteins (Immunoglobulins).
Substances which are produced when
corresponding non-self antigens are introduced into the
body, with which it reacts specifically.
5.
6. Uses of Blood Groups
Red cells are less active cells that contain mainly
hemoglobins. However, they play important role due to the
presence of antigens on their surface.
Characterization of red cell antigen and antibodies forms
the basis of compatibility testing for blood transfusion.
When the blood group of an individual is known, in
emergency situations, blood can be transfused
immediately with the suitable blood. Therefore, ABO and
Rh blood groups are usually displayed in the identity cards
of individuals.
The blood group antigens have provided the scientific basis
for understanding hemolytic diseases of the newborn
and autoimmune hemolytic anemias.
7. Blood group antigens play a critical role in susceptibility
to infections by malaria parasites, bacteria and viruses.
Red cell antigens are also associated with clinical
disorders. Absence is associated with specific
dysfunctions,inherited and acquired diseases
Medicolegal experts take the help of characterization of red
cell antigen and antibodies in establishing the identity of
the father in cases of disputed paternities (mother in
cases of disputed maternity).
Specific blood groups have been reported to be associated
with human behaviors.Thy contribute to the personality
of the individual.
8. Multiplicity of antigens in the
blood cells.
At least 30 commonly occurring antigens and
hundreds of other rare antigens have been found in
human blood.
The most important:
ABO system and Rh system.
9. ABO System
ABO system was the first blood group system to be known
(1901).
This is the most important system in transfusion medicine,
as ABO agglutinogens are highly antigenic.
Physiologically, it is most significant of all blood group
systems, because of natural occurrence of A and B
antibodies in the plasma of individuals who lack
corresponding antigen on their red cells.
In addition, transfusion of incompatible ABO blood groups
instantly leads to serious consequences.
10. ABO Agglutinogens
In ABO system, in essence there are two antigens, the
antigen A and the antigen B. A antigen has two sub-types,
A and A1. The genes for antigens for ABO system are ABO
genes located on chromosome 9.
Occurrence
These antigens are present on the membrane of red cells.
They are also found in other tissues like salivary gland,
testes, lungs, kidney and pancreas. Therefore, they are
secreted in minute quantity in saliva, pancreatic secretion
and seminal fluid.
Some individuals, especially blood group O, secrete blood
group H antigens in saliva and other body fluids; they are
called H secretors (see below, role of H antigen).
11. Antigen and Antibody in ABO
Blood Type
Blood Groups Based on Antigens
Based on the presence or absence of A and B antigens on
the red cell membrane individually or in group, four blood
groups have been described.
Group A : Antigen A is present
Group B : Antigen B is present
Group AB : Both A and B antigens are present
Group O : Neither A nor B antigen is present
Subtypes: As A antigen has two sub-types, A and A1, the
group A is subdivided into two groups: the group A1
containing A and A1 antigens, and group A2 containing A
antigen alone. Similarly, the AB blood group is subdivided
into A1B and A2B blood groups.
12. ABO Agglutinogens…
Distribution
In the Indian population, the approximate
distribution of the ABO blood group is as follows:
A : 27 %
B : 31 %
AB : 8 %
O : 34 %
In the A blood groups, A1 is 75 % and A2 is 25 %.
13. Bombay Blood Group (Phenotype Oh)
Discovered In 1952 by Bhende, Bhatia and Deshpande
These individuals lack the H gene, and therefore the
basic precursor substance can not be converted into H
substance.
This in turn results in failure to form A or B antigen.
When their blood sample is tested for routine AB
grouping, they will be labeled as blood group O.
However, their serum contains anti A and anti B and
anti H antibodies.
These individuals therefore, should be transfused
with only Bombay blood group.
14. ABO Agglutinins
In ABO system, agglutinins are of two types: anti-A (α) and
anti-B (β). The α agglutinin has two subtypes, α proper and
α1.
Occurrence
These antibodies are found in plasma.
Usually, specific antibodies are formed against a particular
antigen, when they are exposed to that antigen.
But, blood group antibodies are naturally occurring
antibodies as they are formed without prior exposure to
the antigens and are present in the blood of individuals in
whom the respective antigens are absent.
15. Time and Mechanism of Appearance
Anti–A and anti-B agglutinins are not formed during fetal life and are
absent at birth.
They appear in the second week of neonatal life and increase very slowly
in concentration to attain the peak level at about 10 years of life.
It has been proposed that intestinal bacteria and food contain
antigens similar to that of blood group agglutinogens. Therefore,
when the baby starts eating and food gets absorbed from intestine,
antigens are absorbed into the blood.
As these antigens are recognized as nonself antigens by the body’s
immune system, they stimulate antibody production.
However, these antigens are present in very low concentration and
antibodies against them are produced very slowly; therefore, antigen-
antibody reaction does not occur. Moreover, antigens are removed by
phagocytic cells.
16.
17. Chemical Nature
The αand β agglutinins are globulins and belong to
Ig M category. Therefore, they do not cross the
placenta.
They function efficiently at low temperature, i. e.
between 5° to 20° C. Therefore, they are called
cold antibodies.
18. Agglutinins against Blood Groups
Antibodies are directed against the antigens.
The individuals with blood group A antigen on the red
cell membrane do not have anti-A antibody, rather possess
anti-B antibody in their plasma.
Persons with blood group B do not contain anti-B, rather
have anti-A antibody in their plasma (Table 16.2)
Individuals with blood group AB do not have any
antibody.
Individuals with blood group O have both the anti-A and
ant-B antibodies in their plasma.
These facts were first noted and described by Karl
Landsteiner in 1900, and his theory is popularly known as
Landsteiner’s law.
19.
20. Landsteiner’s Law
This law states that if a particular agglutinogen is
present on the red cell membrane of an individual,
the corresponding agglutinin must be absent in his
plasma. Conversely, if the agglutinogen is absent in
the red cells, the corresponding agglutinin must be
present in the plasma. This law holds good for ABO
system. However, the second part of the law does not
apply for Rh and many other blood group systems as
there are no naturally occurring agglutinins in these
systems.
21. Antigen & Antibodies for ABO Blood
Groups
Thus, in ABO system, blood group A has antigen A
on the red cell membrane and anti-B antibody in the
plasma, blood group B has antigen B on the red cell
membrane and anti-A antibody in the plasma,
blood group AB has both antigens A and B on the
red cell membrane and no antibodies in the plasma,
and blood group O has no antigens on the red cell
membrane and possesses both agglutinins anti-A
and anti-B in the plasma (Table 16.2).
22.
23. Blood Grouping
Blood grouping is performed by suspending the
red cells of the person’s blood group to be checked
in the anti-A and anti-B antisera that are
commercially available.
If the agglutination (clumping of red cells, as
checked under the microscope) is present, red
cells contain that particular antigen
24.
25. Inheritance of ABO Blood Groups
Blood groups are genetically determined. Normally, presence
of a blood group antigen is a dominant characteristic.
Therefore, the antigen is present in the phenotype
irrespective of the genotype.
There are three types of genes: O, A and B.
Therefore, a person can have any of the six possible
genotypes: OO, OA, OB, AA, BB, and AB.
Gene O is genetically not important.
Therefore, the respective phenotype may be A or B or AB
or O.
For example, if blood group of one parent is A and other
parent is B, then there is possibility of child having any of
the four blood group of ABO system (Fig. 16.3).
26.
27.
28. The Rh System
The Rh (Rhesus) system is the second most important
blood group system in transfusion medicine.
This was first described in Rhesus monkeys in 1940 by
Landsteiner and Weiner; hence it is called Rh system
(for Rhesus).
First, it was discovered that injection of red cells of
Rhesus monkey into rabbit results in development of
antibody against rhesus red cells, later it was found
that rabbit serum containing anti-Rhesus antibody
agglutinate human red cells.
This led to the discovery of Rh system in humans.
29. Rh Antigens
In Rh system, there are six antigens, but there are no
naturally occurring antibodies. The antigens are C, D, E, c, d
and e. Out of these six antigens, immunologically most active
is the D antigen.
Thus, in Rh system, there are two blood groups: Rh
positive (D antigen present) and Rh negative (D antigen
absent).
The gene for Rh antigen is the RHD and RHCE genes that
are located on chromosome 1.
The antigens of Rh system participate in cation transport
and membrane integrity of red cells.
Rh antigens are membrane proteins found in red cell
membrane, not in any other tissues.
30. Rh Antigens
Inheritance
Rh antigen is inherited as dominant gene.
In Indian population, 95 to 98% are Rh +ve and 2 to 5% are Rh –ve.
Rh +ve individual may have homozygous (DD) or heterozygous (Dd)
genotypes. Usually, 60% of Rh +ve individuals have Dd genotype and
40% have DD genotype. The genotype of Rh –ve person is dd.
If one of the parents is homozygous positive and the other is
homozygous negative, all offsprings will be heterozygous positives (Fig.
16.4).
Similarly, if the father and mother are homozygous negatives, all
offsprings will be homozygous negatives, and when one of the parents
is heterozygous positive and the other homozygous negative, 50% of
offsprings will be heterozygous positive and 50% will be homozygous
negatives.
31.
32. Rh Antibody
The antibody in the system is called anti-D antibody,
which is produced only when an Rh negative
individual receives the Rh positive blood.
These antibodies develop very slowly in the first
encounter, but form rapidly following subsequent
encounters. Rh antibody is of Ig G type, which can
cross placental barrier.
Hence, if antibodies are present in mother’s blood, can
be transferred to the fetus.
Rh antibody is best reactive at body temperature, and
therefore, designated as warm antibody.
33. Rh Incompatibility
Rh incompatibility occurs when an Rh negative individual receives
Rh positive blood.
Normally, when an Rh negative person receives Rh positive
blood, there will be no immediate reactions as Rh negative
individual does not normally has anti-Rh antibody.
However, the donor’s red cells induce an immune response in the
recipient to synthesize anti-Rh antibodies, which takes about
two to four months to reach a significant titer.
However, by that time the donor’s red cells die their natural
death within 120 days.
The anti-Rh antibody cannot produce any harm to the recipient’s
red cells because the Rh-negative recipient’s red cells contain no
Rh antigens.
34. But, if the same Rh negative person who has already
received a Rh positive blood before, receives a second
Rh positive transfusion later, the anti-Rh antibodies
are synthesized in large amount immediately by the
memory cells.
This antibody reacts against the donor cells and causes
reactions of mismatch transfusion.
Thus, the Rh negative individual can safely receive
Rh positive blood once in life time.
The similar Rh incompatibility occurs in pregnancies
when Rh negative mother bears Rh positive fetus, which
leads to erythroblastosis fetalis.
35. Erythroblastosis Fetalis
Etiopathogenesis
This is a hemolytic disease of the newborn which occurs due
to Rh incompatibility when an Rh negative mother carries Rh
positive fetus during pregnancy.
Usually, no reaction occurs in the first pregnancy. However, at
the time of delivery during placental separation, a small
amount of fetal blood leaks into the maternal circulation.
This induces formation of anti-Rh agglutinins in the mother.
In subsequent pregnancies, the anti-Rh agglutinin from
mother, which is predominantly IgG type crosses placenta to
enter the fetal circulation and causes hemolysis.
In third and subsequent pregnancies, the degree of hemolysis
becomes severe.
36. Erythroblastosis Fetalis….
Clinical Features
The features are mainly due to hemolysis. Hemolysis leads
to anemia, extramedullary hemopoiesis and neonatal
hyperbilirubinemia. If the hemolysis is severe, the fetus
may die in utero or if the fetus is born alive, he may have
the following features.
Anemia: Anemia is proportionate to the degree of
hemolysis.
Hemolytic jaundice: Occurs due to hemolysis. Serum
bilirubin level may be more than 25mg% in severe cases.
Generalized edema: Edema occurs in the whole body due
to anemia and hypoproteinemia. This is called hydrops
fetalis.
37. Erythroblastosis Fetalis….
Kernicterus: This is a neurologic syndrome with major motor
deficits that occurs due to the deposition of bilirubin in the basal
ganglia.
Hyperbilirubinemia occurs due to hemolysis.
Basal ganglia have more affinity for bilirubin. However, bile
pigments cannot cross the blood-brain barrier (BBB) in adults.
Therefore, hemolysis in adults does not produce kernicterus.
As BBB is not fully developed in fetuses, infants and children,
in them bilirubin enters brain and gets deposited in the basal
ganglia.
Therefore, hemolysis in infancy and early childhood causes
kernicterus.
The dysfunctions mainly manifests in the form of motor
dysfunctions.
38. Extramedullary hemopoiesis:
Due to severe anemia, extramedullary hemopoiesis
occurs, for which erythroblasts (nucleated red
cells) are released into the blood.
Erythroblasts are seen in plenty in peripheral smear.
Hence, the disease is called erythroblastosis fetalis.
39. Erythroblastosis Fetalis….
Treatment
About 50% of the fetuses and newborns with erythroblastosis
fetalis have mild hemolysis and do not require treatment.
In severe cases, the major modalities of treatment are
intrauterine fetal transfusion, exchange transfusion and
phototherapy.
Intrauterine fetal transfusion: If the disease is
diagnosed in fetus and found to be severe, the treatment is
intrauterine fetal transfusion.
Presently, the fetal transfusion is carried out by
intraperitoneal route, which has replaced the direct
intravascular fetal transfusion.
40. Exchange transfusion:
The treatment of newborns with severe anemia, jaundice and
hydrops is exchange transfusion soon after birth.
Exchange transfusion removes sensitized red cells, bilirubin and
maternal antibody from the plasma.
A double-volume exchange transfusion (2 x 80 ml/kg) replaces
90% of the infant’s blood volume with antigen negative red cells.
Blood chosen for exchange should be ABO negative, Rh negative
and cross-matched against mother’s blood.
Phototherapy:
Intensive phototherapy is very effective in reducing serum
bilirubin level
41. Erythroblastosis Fetalis….
Prevention
Erythroblastosis fetalis is prevented by
administering a single dose of anti-Rh antibodies
in the form of Rh immunoglobulin during the
post-partum period following the first delivery.
The disease can also be prevented by passive
immunization of the mother with a small dose of
Rh immunoglobulins during pregnancy.