Documente Academic
Documente Profesional
Documente Cultură
ABO ANTIGENS
In the 1901, Karl Landsteiner discovered the ABO blood group antigens. By
systematically mixing the RBC from a number of individuals with the sera
from others, he found that the RBCs from some individuals were agglutinated
by the sera from others. A pattern of four major groups emerged- A, B, AB, or
O. Individuals have either A or B antigen on their cells, a combination of A&B,
or neither (group O).
Antibodies are usually not present at birth but are present in most
individuals by about 6 mons of age. During this period the infant is
exposed to a variety of microorganisms and foodstuffs which have
antigenic determinants that are cross reactive with the blood group
substances and which can thus provide the stimulation for isoantibody
formation (ie E. coli has type B like Ag). These cross reacting Ags
induce formation of Abs in individuals lacking these antigens. An
individual with type A blood however does not respond to A like
epitopes on intestinal microorganisms because these A-like epitopes are
too similar to self and a state of self tolerance to these epitopes should
exist. Therefore, even though induced by microbial Ags, the Abs react to
similar oligosaccharides on RBCs. Natural isoAbs are usually of the
IgM class. Abs arising as a result of a mismatched transfusion are
usually of the IgG class.
The blood group antigens are genetically determined with each antigen
controlled by two alleles, with A & B alleles codominant to the O allele.
A2A2, A2O A2
BB, BO B B=10
A2B A2B
OO O O=46
The blood group substances A & B are found in the body secretions
(saliva, semen, gastric juices, sweat) of about 75% of persons (secretors)
with these blood groups. The secretion is also genetically determined
and controlled by two alleles: Se and se with Se being dominant. The
blood group antigens are also found on liver, muscle, spleen, kidney and
lung cells. It is therefore possible to determine the blood type of an
individual by examination of any tissue.
The ABO RBC antigens are cell surface heterosaccharides. ABO Ags
are not primary gene products but instead they are enzymatic reaction
products catalyzed by enzymes called glycosyltransferases. All normal
individuals synthesize a common core glycan called the H Ag (type O)
that is attached to a polypeptide backbone. Individuals who possess an A
allele gene product form an enzyme that adds a terminal N-
acetylgalactosamine to some of their O Ags for the A Ag. The B allele
enzyme adds a terminal galactose. Type O blood does not lack Ag-
instead have H substance.
A1 red blood cells have about one million A antigens per cell. A2 red
cells have only 250,000 A antigens per cell, or one-fourth the amount
that A1 cells have.
The 'A' antigen on A1 and A2 subgroup blood cells is named 'Type 2 A'
antigen; however, A1 subgroup blood cells also have two additional
forms of antigen as well, 'Type 3 A' and 'Type 4 A', neither of which
appear on A2 subgroup blood cells.
Other blood group systems have been discovered recently. Today some 20
human systems, which include 60 different blood group factors are known.
The antigens of one of these the Lewis system are involved in the chemical
structure of the ABO system antigens. In general, differences in minor blood
groups lead to red cell lysis only after repeated transfusions produce a
secondary Ab response.
Transfusion Reaction
The chief danger from incompatible transfusions lies in the fate of the
injected cells. The patient may suffer a transfusion reaction if there is sufficient
Ab in his circulation to cause agglutination or hemolysis of the donor’s RBCs.
Lysis of the RBCs lead to free hemoglobin that can be detected in the
plasma and it is filtered through the kidneys.
Treatment involves
Rh
The Rh factor is not the single entity as originally thought but a complex
system of antigens. Initially 3 pairs of closely linked allelic genes were
postulated by Fisher and called Cc,Dd, and Ee. There are actually more than 30
subgroups of these factors but for practical purposes the D ( or Rho in the
Weiner system) antigen proved to be the strongest and most potent
antigenically and therefore the most important in hemolytic disease and in
transfusion reactions.
There are antigens for each of these factors so there is antiserum available for
each one except anti-d so we have to employ statistical studies to determine
zygosity of D.
If a person has Big C and Big E present, regardless of the zygositiy, then
most likely that person is homozygous for D.
The problems occur with each successive Rh+ fetus. Fetal antigens can
leak into the mother's circulation which can result from hard coughing or
sneezing. This triggers a secondary Ab response (activates memory B
cells) so IgG is produced this time. IgG can cross the placenta and
attack the RBC of the fetus and cause jaundice due to excessive bilirubin
in their blood.
Coomb’s test
Unlike the ABO system, the corresponding antibodies for the Rh antigens
do not occur naturally, but as the result of immunization.
The Rh Ags are also widely spaced on the RBC surface, the IgG
anti Rh Abs cannot fix complement and cause lysis of the RBC in
vitro.
Direct Test- The infants RBC are washed and anti-globulin serum is added-
agglutination will occur if the mother’s Ab is coating the RBC as is seen in
Erythroblastosis Fetalis.
Indirect Test- maternal serum which potentially contains the anti-Rh Ab is incubated
with Rh+ test cells. Then anti-Ab is added. If anti-Rh Abs are present on the RBCs then
agglutination will occur.