6th lesson Medical students Medical Biology
Blood group system
ABO system
ABO, the most important blood group system from the clinical blood transfusion perspective, was discovered in 1900 by Landsteiner, the discovery that first made blood transfusion feasible. At its basic level, there are two ABO antigens,Aand B, giving rise to four phenotypes, A, B, AB and O. In the O phenotype, neither A nor B is produced . Group A people generally have anti-B in their plasma, group B people have anti-A, group AB people have neither antibody, and group O people have anti-A,B. These are predominantly agglutinating immunoglobulin (IgM) antibodies. Anti-A,B will agglutinate group A or B cells. In transfusion medicine it is imperative that donor red cells that are agglutinated by the patient’s plasma are nottransfused. "Natural" antibodies called isoagglutinins exist in an individual's serum, directed against whichever of the A and B antigens is not present on that person's red cells.The presence of ABO antigens and antibodies (isoagglutinins) in the four blood types is summarized below:
The success of blood transfusions depends on ensuring the compatibility of the blood typesbetween donor and recipient. If the recipient has antibodies to the infused red cells, these redcells will be rapidly destroyed, resulting in a potentially lethal transfusion reaction. Type Ablood given to a type B recipient, for instance, can result in such a reaction, since therecipient's serum contains anti-A antibodies.
Structure of ABO antigens; "natural antibodies"
Why are there so-called "natural" antibodies to A and B blood group antigens? A description of the nature and distribution of these antigens will help answer this question. The blood group substances A and B represent two modified forms of a "stem" carbohydrate present on red blood cells and other tissues. Their structures are shown below (where GLU is glucosamine, GAL is galactose or galactosamine, FUC is fucose, and NAc represents an Nacetyl group):
These same carbohydrates are also a common component of many foods we eat and manymicroorganisms in our intestinal tract. The immune system is therefore constantly exposedto these antigens, and responds by making an effective humoral response. Since the immunesystem does not in general respond to antigens which are a normal part of "self", a type B individual does not make antibodies to the B blood groupsubstance, although the response to the type A antigens is robust. The net result is theproduction of antibodies, mostly of the IgM class, to whichever of these substances is notpresent on an individual’s red blood cells.It is important to remember that the A and B blood group substances are present not only on red blood cells, but also in virtually every other tissue. They are therefore important transplantation antigens and must be taken into account together with HLA tissue-typing, when organ transplantation is performed.
Genetics of ABO
The presence of A and B carbohydrates in our tissues is determined by three alleles at a single genetic locus. One allele encodes an enzyme which produces the A substance, another the B substance; and when both of these alleles are present in a heterozygote both carbohydrates are made. The third allele, O, behaves essentially as a "null" allele, producing neither A nor B substance. Only a single genotype can produce the phenotype AB, namely the heterozygous state A/B. Likewise, type O individuals must be homozygous O/O. However, type A or type B individuals can be either homozygous or heterozygous, the O allele being effectively recessive since it does not contribute either of the two antigens. The inheritance of the ABO blood groups follows simple Mendelian rules. For instance, a homozygous type A mother and a type AB father can yield only two kinds of offspring, type A (genotype A/A) or type AB (genotype A/B). A heterozygous type A and a heterozygous type B, on the other hand , can yield four genotypes and four corresponding phenotypes.
The ABO gene is autosomal (the gene is not on either sex chromosomes). The ABO gene locusis located on the chromosome 9. Aand B blood groups are dominant over the O blood group.A and B group genesare co-dominant. This meant that ifa person inherited one A group gene and one B group gene their red cells would possess both the A and B blood group antigens. These alleles were termed A (which produced the A antigen), B (which produced the B antigen) and O (which was "non functional"and produced no A or B antigen).
Charts show the possible blood type results for offspring
Mother's type / Blood TypeAB / B / A / O
A, B / O, B / O, A / O / O / Fathers' type
A, B, AB / O, A, B, AB / O, A / O, A / A
A, B, AB / O, B / O, A, B, AB / O, B / B
A, B, AB / A, B, AB / A, B, AB / A, B / AB
Rh system
Rh is the most complex of the human blood group systems, with 45 well defined antigens. The most immunogenic andclinically important antigen of theRhsystem is D.The other main polymorphisms of the Rh system are C/cand E/e, two pairs of allelic antigens.Before the 1970s, anti-D was the most common cause ofhaemolytic disease of the newborn (HDN). Injection of Dnegativewomen with anti-D immunoglobulin within 72 hours of giving birth to a D-positive baby prevents the mothersfrom producing the anti-D that could damage theirsubsequent babies. This prophylactic procedure has madeHDN due to anti-D relatively rare.
The antigens of the Rh system are encoded by two genes,RHCE and RHD. These genes are highly homologous andclosely linked on chromosome 1.
Mother's Type / Rh FactorRh –(r) / Rh +(R)
Rh + Rh –(Rr) / Rh + Rh +(Rr) / Rh +(R) / Father's Type
Rh –(rr) / Rh + Rh –(Rr) / Rh –(r)
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