33. Human alloantigens. Blood group antigens ABO (H), Se and Rhesus.

Blood group alloantigens. ABO and H blood groups

Introduction to Blood Group Alloantigens

• Blood transfusion is a type of transplantation, where the donor’s red blood cells are introduced into the recipient’s bloodstream.
• Red blood cells (erythrocytes) do not express MHC (major histocompatibility complex) molecules, so they do not trigger a strong T-cell mediated immune response.
• However, red blood cells carry polymorphic surface carbohydrates and proteins that differ among individuals and can stimulate a strong antibody (humoral) immune response.
• These polymorphic molecules are called blood group antigens, and individuals with different forms of these antigens belong to different blood groups.
• A blood group system refers to a set of antigens controlled by alleles of a single gene. There are several systems, but ABO and Rhesus are the most clinically significant.

ABO Blood Group System

• Discovered by Karl Landsteiner, the ABO system was the first to be understood and is the most crucial for transfusion safety.
• Landsteiner noticed that mixing blood from different people sometimes caused agglutination or clumping of red cells, revealing incompatibility.
• There are four main blood types in this system: A, B, AB, and O.
• Blood group A has antigen A.
• Blood group B has antigen B.
• Blood group AB has both antigens A and B.
• Blood group O has neither antigen A nor B.

Chemical Nature and Biosynthesis of ABO Antigens

• Unlike most antigens, ABO blood group antigens are carbohydrates, not proteins.
• These antigens are part of glycoproteins and glycolipids on the outer surface of red blood cells, collectively forming the glycocalyx.
• A common precursor oligosaccharide is present in all individuals.
• This precursor is modified by glycosyltransferase enzymes, which are encoded by specific genes.
• The FUT1 gene (also called the H gene) adds a fucose molecule to the precursor, forming the H antigen.
• The ABO gene has three main alleles: A, B, and O.
• The A allele encodes transferase A, which adds N-acetylgalactosamine to the H antigen, forming antigen A.
• The B allele encodes transferase B, which adds galactose to the H antigen, forming antigen B.
• The O allele is inactive and produces no enzyme, so the H antigen remains unmodified.
• These enzymes determine which antigens appear on the red cell surface.

ABO Genotypes, Phenotypes, and Antibody Production

• Individuals produce antibodies against the A or B antigens they do not have.