Blood Group Serology (Immunohaematology)
BLOOD GROUP GENETICS
Terms Commonly used in Genetics
BLOOD GROUP ANTIGENS
BLOOD GROUP ANTIBODIES, Alloantibodies
MAIN BLOOD GROUP SYSTEMS
ABO BLOOD GROUP SYSTEM
Laws of inheritance of ABO Groups,
Subgroups of ABO, Natural Antibodies of ABO System,
Immune Response to Blood Group Antigens
Haemolytic Disease of the New-born (HDN)
CLINICALLY LESS SIGNIFICANT BLOOD GROUP SYSTEMS
The
Sex-Linked Antigen,
Blood Group Serology (Immunohaematology)Blood Group Serology (Immunohaematology)
Each species
of animals, including humans, has D certain inherited antigens on the surface
of the red cells which are unique for that species. These are known as
isoantigens. Similarly, certain antigens, the alloantigens are common to some,
but not all, members of that particular species. Blood group serology involves
the detection of these antigens and their antibodies.
BLOOD GROUP GENETICS
All the
antigenic substances present on the red cells of an individual are inherited.
The unit of inheritance is a gene and each antigen is controlled by a gene for
that antigen. Genes are made up of deoxyribonucleic acid (DNA) which, when
organised in a linear form, make up a chromosome.
Humans have 23 pairs of chromosomes in each nucleated cell. The genes responsible for a particular character always occupy the same position on a par ticular chromosome. The position of each gene on a chromosome is called its locus, Genes are always arranged in the same sequence on a chromosome.
Humans have 23 pairs of chromosomes in each nucleated cell. The genes responsible for a particular character always occupy the same position on a par ticular chromosome. The position of each gene on a chromosome is called its locus, Genes are always arranged in the same sequence on a chromosome.
Some Terms Commonly used in Genetics
Allele
or allelomorph Two or
more genes responsible for the same characteristic occupying the same position
on the chromosomes.
Homozygous A person who
has inherited same allelic genes from both parents e.g. having both blue eyed
colour genes.
Heterozygous A person
who has inherited different allelic genes for a traite.g. having a blue and
brown-eye colour genes.
Dominant gene Certain
alleles are stronger than other alleles. For example, brown eye genes mask the
presence of blue eye genes, and are therefore dominant over blue eye genes. A
dominant gene expresses itself in both homozygous and heterozygous
states.
Recessive gene The recessive genes are expressed only when their dominant allele is
absent e.g. only in the homozygous state. That is, the colour of the eye will
be blue if both the alleles are for blue eyes.
Co-dominant gene In a co-dominant gene, various alleles for the same character are equally
dominant.e.g. alleles for a particular blood group system,
Genotype The
genetic make up of an individual or a cell is called its genotype.
Phenotype It
is the observable characteristics of an individual or a cell. e.g. an
individual of group BO genotype would be expressed as group B because O gene is
recessive.
BLOOD GROUP ANTIGENS
The blood
group antigens include substances on the red blood cells and on other blood
constituents such as leucocytes, platelets and plasma. The blood constituent
antigens, which are governed by a single gene or a group of genes, are
inherited as 'groups'. Blood groups controlled by a set of genes are called a
blood group system. Most blood group antigens follow the laws of inheritance.
Chemically, blood group antigens are usually glycoproteins, lipoproteins or
glycolipids in nature.
BLOOD GROUP ANTIBODIES
Specific
blood group antibodies develop in response to the antigenic stimulation by a
particular blood group antigen. The level of antibody activity depends on the
immunogenicity of the corresponding antigen.
Alloantibodies
Alloantibodies are
antibodies which are present in some members of a species, but not all. For
example, anti-A antibodies are present in all human beings belonging to blood
group B and O. Due to the presence of alloantibodies, it is necessary to select
a blood donor who is negative for the corresponding antigen i.e. if a recipient
has anti-A antibodies, he cannot receive blood which contains group A antigen.
Alloantibodies to red cell may be of three types:
(i)
Naturally occurring i.e. the antigenic stimulus is unknown. ABO antibodies
belong to this type.
(ii) As a
result of immunisation through transfusion, some red cell antigens which are
absent in the recipient may be introduced and induce antibody production.
(iii)
Induced by exposure to foetal erythrocytes either during pregnancy or during
delivery. These antibodies are similar to those produced by blood transfusion.
Development of Rh antibodies in a Rh negative mother by a Rh positive foetus is
a good example.
Autoantibodies
An
autoantibody is the antibody which is induced by an antigen in the same
individual. It also reacts with the same antigen if it is present in other
individuals. In some cases, the reaction of the antigen and its autoantibody
may not show any demonstrable clinical symptoms, whereas sometimes such a
reaction may lead to haemolytic anaemia, leucopenia or thrombocytopenia.
Autoantibodies are divided into two general categories depending on their optimum reacting temperature.
(i) Warm autoantibodies These
constitute about 85% of the autoantibodies. Their optimal reacting temperature
is 37°C. Warm autoantibodies are generally IgG in nature and can be detected
with the direct antibody test (DAT).
(ii) Cold autoantibodies About
15% of the autoantibodies are of this type. They are generally IgM in nature
and agglutinate red blood cells strongly at 4°C, weakly at 24°C and not at all
at 37°C. Most of autoantibodies are present in normal individuals, very few are
associated with diseases.
It is important to be aware of cold antibodies when the patients body temperature needs to be lowered for procedures such as cardiopulmonary bypass.
It is important to be aware of cold antibodies when the patients body temperature needs to be lowered for procedures such as cardiopulmonary bypass.
MAIN BLOOD GROUP SYSTEMS
Approximately
600 blood group antigens have been described so far. These are inherited stable
characteristics and therefore are useful in paternity testing. The knowledge of
blood group antigens is important in blood transfusion. If a recipient lacks a
particular blood group antigen, he may produce antibodies against that antigen
leading to a transfusion reaction. Different blood group antigens have varying
degrees of antigenicity. The ABO and Rhesus groups are of major clinical
significance. There are many other systems of less importance.
ABO BLOOD
GROUP
|
|||
Phenotype
|
Geno type
|
Antigen
|
Neurally – occurring antibodies
|
o
|
OO
|
NONE
|
Anti-A, B
|
A
|
AA or AO
|
A
|
Anti -a
|
B
|
BB or BO
|
B
|
Anti-A
|
AB
|
AB
|
A
|
NONE
|
ABO BLOOD GROUP SYSTEM
 |
ABO GROUPING system |
(i) Strongly
reactive antibodies are present in the serum of individuals who lack the
corresponding antigens.
(ii) A and B
antigens are present on many tissue cells in addition to the red cells.
The ABO system consists of four blood groups or phenotypes: A, B,
AB and O. The two antigen, A and B are responsible for these four groups. If A
antigen is present on the red cell, the individual is said to belong to group
A, those having B antigen are group B persons. Group AB individuals have both A
and B antigens while group O persons have neither A nor B antigen on their red
cells. (Table 8.1). Three allelic genes, A, B and O. can be inherited in the
ABO system. The following combinations of alleles is possible: AA, AO, AB, BB,
BO, 00, resulting in A, A, AB, B, B, and O group individuals respectively. This
is so because A and B genes are dominant and O gene is recessive.
Laws of inheritance of ABO Groups
According to Bernstein's theory, two laws of inheritance have
been proved.
1. It is not
possible that an offspring can possess antigen A, B or both unless it is
inherited from one or both parents (Fig 8.1). .
2. A parent
of blood group AB cannot produce an offspring of group O. Similarly, a parent
of blood group O can not produce AB offspring. The reason for this law is that
group AB is heterozygous, and therefore A and B genes must come from two
parents. Table 8.2 shows the possible ABO phenotypes of offsprings.
POSSIBLE ABO
PHENOTYPES OF OFFSPRING
|
|
PHENOTYPES OF PARENTS
|
POSSIBLE PHENOTYPES
OF OFFSPRING
|
O × O
|
O
|
O × A
|
O or A
|
O × B
|
O or B
|
O × AB
|
A or B
|
A × A
|
A or O
|
A × B
|
A, B, AB or O
|
A × AB
|
A, B, orAB
|
B × B
|
B or o
|
B × AB
|
A, B or AB
|
AB ×AB
|
A,B or AB
|
Group O
individuals have an antigen called Hantigen on the surface of their red cells
which is a precursor of A and B antigen. The original classification of the ABO
system was made by Karl Landsteiner in 1900. Although other cells in the body
have ABO antigens, only ABO antigens on red cells play an important role in
blood transfusion reactions.
Subgroups of ABO
Both groups
A and B can be further subdivided. The most important of these subgroups are A,
and A Both A, and A, cells react with anti-A antiserum. Approximately 20% of
group A and AB persons belong to subgroup A, and 80% to A,. There are some more
subgroups of A, but they are rare and produce weak reactions. Several subgroups
of B have been identified but they are very rare.
H Substance and Bombay Group
Another
gene, H, is inherited independently of ABO. The H substance produced by the H
gene is a precursor for A and B antigens. Therefore, this gene is necessary for
the synthesis of AB antigens, and is present in 99.9% of the population. The H
gene may have a silent-allele, h. In an homozygous hh individual, even if ABO
genes are present, the precursor
for the
synthesis of these antigens is not produced in the absence of H gene. (Fig
8.2). This rare blood group is called Bombay group (Oh) as it was discovered in
this city. The Bombay group is only a phenotypic expression because these
individuals do possess ABO genes. If offsprings of a Bombay individual (hh)
receive an H gene from the other parent, they will exhibit normal AB antigens.
Because A
and B antigens are absent in Bombay group individuals, they are typed as group
O persons with anti-A and anti-B sera. Only anti-H can detect the Bombay blood
group. While other groups will give a positive reaction with anti-H serum, the
Bombay group will give a negative reaction.
Se gene Se
is another independent gene involved in ABO expression. Individuals possessing
Se gene have respective A, B and H antigens (according to their genotype) in
their secretion and body fluids such as saliva, tears, milk and urine. These
persons are called 'secretors' and form about 80% of the population. The
non-secretor status is due to the presence of the silent allele se (genotype
sese) on both the chromosomes.
Natural Antibodies of ABO System
Individuals
whose red cells lack A, B or both antigens have the respective antibody in
their sera
(Table 8.1).
This is known as Landsteiner's rule. These antibodies are not present at birth.
Infants start producing them after 3-6 months of age. AntiA and anti-B reach
peak levels between 5 to 10 years and then the titre gradually declines. The
ABO antibodies are absent in infants, elderly persons, and in pathological
conditions which affect antibody production.
ABO
antibodies are the most important of all other blood group antibodies.
Transfusion of an incompatible blood can cause a severe transfusion reaction.
These antibodies are potent haemolysins and can bring about intravascular
haemolysis. The antibodies are of both IgG and IgM types, and can bind to
complement
As ABO
antigens are also present on the tissue cells, their antibodies can cause rapid
organ rejection in the transplantation of highly vascularised organs. ABO IgG
antibodies can cross the placenta during pregnancy and may cause haemolytic
disease of the new-born (HDN) in an antigen positive foetus. However, HDN due
to ABO antibodies is rarely severe because the development of antigens in the
new-born is incomplete and the infant's soluble antigens have a neutralising
effect.
Immune Response to Blood Group Antigens
Exposure to
non-self (foreign) red cell antigens may not always result in the production of
antibodies. Antibody production depends on a number of factors:
1.
Immunogenic potential of the antigen Some antigens are more immunogenic than
others e.g. Rhesus (Rh) antigen is a very potent immunogen.
2. Dose of
the antigen At the initial exposure to the antigen, a large dose of antigen is
necessary to stimulate antibody production.
3.
Immunocompetence of the individual Individuals vary in their ability to respond
to antigenic stimulation. Some disease states may depress or amplify immune
function.
Primary
response to blood group antigens after the first exposure requires several
weeks, if the concentration of the antibody is low, and the titre declines
within a short period. These antibodies are predominantly IgM type.
Secondary
response upon the next exposure to the same antigen, on the other hand, is more
rapid, requires a much lower dose, results in the production of larger amounts
of antibody, and a higher titre is maintained for a much longer period. These
antibodies are IgG in nature.
ABO GROUPING - Click here
ABO GROUPING METHODS - Click here
1.
RHESUS (Rh) GROUPING
SYSTEM - click here
a.
Rh Antigens
b.
The D' Antigen
c.
Rh Typing Methods
2.
METHOD 1: SALINE METHOD FOR Rh-D TYPING USING
COMPLETE ANTI-D
A.
Slide Test
B.
Tube Test
3.
METHOD 2: ALBUMIN DISPLACEMENT TECHNIQUE FOR RE
TYPING USING INCOMPLETE ANTI-D
4.
METHOD 3: ENZYME TECHNIQUES
Haemolytic Disease of the New-born (HDN)
Haemolytic
disease of the new-born, also known as erythroblastosis foetalis, occurs when a
child inherits an antigen from the father which is absent in the mother. It may
result from incompatibilities of any blood group system, but the most commonly
involved factors are those of the Rh and ABO systems. For HDN to occur, the child
must be positive for a particular antigen, and the mother must be negative for
the same antigen.
Mechanism
The mechanism of HDN involves sensitisation of the mother to the foreign
antigen present on the child's red cells. Normally, while the foetus is in the
uterus, mixing of the mother's and foetus blood does not occur because only
small molecules can pass through the placenta, and the circulatory systems of
the mother and the foetus are separate. However, a small amount of the child's
blood can enter the mother's circulation during childbirth, and the antibody is
produced by the mother subsequently. This antibody, which is of the IgG type,
may then cross the placenta in the next pregnancy, resulting in the destruction
of the red cells of the foetus.
HDN most
often involves D antigen of the Rh system, the mother being Rhesus negative,
and the father positive. Only the children who are Rh-D positive can be
affected by the disease. However, the first child is rarely affected, and less
than 20% of Rh-negative mothers are sensitised during childbirth. Once
sensitised, all the other Rh-D positive foetuses will suffer from HDN.
Other
antibodies causing HDN include anti-c, anti-E, anti-K (Kell) and antibodies
produced due to incompatibilities of the ABO system. The incidence of HDN has
been dramatically reduced after the introduction of Rh immune globulin (RhIG).
If RhIG is given to an Rh-D negative mother within 72 hours of delivery of an
Rh-D positive child, the production of anti-D antibodies is suppressed.
When HDN does occur, the destruction of child's red cells by mother's antibody results in clinical jaundice. If the serum bilirubin level is high, it may lead to brain damage and mental retardation. The treatment for HDN is 'exchange blood transfusion, in which the child's blood is replaced with blood without the antigen responsible for HDN e.g. Rh-D negative blood.
When HDN does occur, the destruction of child's red cells by mother's antibody results in clinical jaundice. If the serum bilirubin level is high, it may lead to brain damage and mental retardation. The treatment for HDN is 'exchange blood transfusion, in which the child's blood is replaced with blood without the antigen responsible for HDN e.g. Rh-D negative blood.
CLINICALLY LESS SIGNIFICANT BLOOD GROUP SYSTEMS
Besides the ABO and Rh systems, there are a large number of
other antigens detectable on a human red cell. Some of these antigens have been
identified to form distinct systems similar to ABO and Rh systems, but they are
clinically much less sig. nificant. Some of such blood group systems most
commonly encountered in clinical situations are described below.
Lewis Blood Group System (Le)
P Blood Group System
MNSs Blood Group Systems
Kell Blood Group System
Duffy Blood Group System
Kidd Blood Group System
LW Blood Group System
Lutheran Blood Group System
The Sex-Linked Antigen
This
sex-linked (X-chromosome) antigen, Xg has a unique feature that it is more
likely to be present in women than in men, because women have two Xchromosomes,
while men have only one. Men never inherit it from their fathers, because the
single xchromosome they possess is inherited from their mothers.
On the other hand, daughters of men who are positive for this antigen (Xg) always inherit it from the fathers. Anti-Xg" is a rare antibody. It can be detected by the antihuman globulin technique, but is destroyed in the enzyme technique.
On the other hand, daughters of men who are positive for this antigen (Xg) always inherit it from the fathers. Anti-Xg" is a rare antibody. It can be detected by the antihuman globulin technique, but is destroyed in the enzyme technique.
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