5.2 Lecture - Blood Types: Agglutinogens and Agglutinins

• Blood is classified into four major types: O, A, and B, based on the presence or absence of A and B agglutinogens.
• Type O blood lacks both A and B agglutinogens.
• The blood group genetic locus has three alleles.
• The type O allele is nonfunctional and recessive to both A and B alleles.
• Presence of the O gene combined with A or B results in A or B phenotype.
• There are at least 30 common and hundreds of rare antigens on human blood cell membranes.
• When type A agglutinogens are absent, anti-A agglutinins develop and when type B agglutinogens are absent, anti-B agglutinins develop.
• Type B blood contains anti-A agglutinins.
• Type A blood contains anti-B agglutinins.
• Type O blood contains both anti-A and anti-B agglutinins.
• Agglutinins form between 2 and 8 months after birth.
• Anti-A or anti-B plasma agglutinins mix with red blood cells containing A or B antigens, the agglutinins attach to the red blood cells.
• Agglutinins attach to red blood cells because they have two binding sites (IgG) or ten binding sites (IgM).
• A single agglutinin can attach to multiple red blood cells simultaneously, which causes clumping or agglutination.
• Agglutination causes clumps that plug small blood vessels, and are then attacked by phagocytic white blood cells, causing the release of hemoglobin into the plasma.
• Activation of the complement system and formation of the membrane attack complex can cause immediate hemolysis of red blood cells.
• For blood typing, RBCs are separated from plasma, diluted with saline, mixed with intact agglutinins, and observed under a microscope for clumping, which indicates an antibody-antigen reaction.

RH Blood Types

• There are six common types of Rh antigens, each called an Rh factor: C, D, E, c, d, and e.
• A person with a capital letter antigen does not have the lowercase version, and vice versa.
• Type D is most prevalent and antigenic.
• Individuals with the D antigen are Rh positive; those without are Rh negative.
• Rh-negative individuals can still experience transfusion reactions from other Rh antigens, though milder.
• When an Rh-negative person receives Rh-positive blood, anti-Rh agglutinins develop slowly, reaching maximum concentration in about four months.
• Subsequent transfusions of Rh-positive blood can cause a sudden and severe reaction when sufficient antibodies have developed.

Erythroblastosis Fetalis

• Erythroblastosis fetalis typically occurs when the mother is Rh-negative and the father is Rh-positive, resulting in an Rh-positive fetus.
• The mother develops anti-Rh agglutinins upon exposure to the fetus's Rh antigens.
• Maternal agglutinins cross the placenta and cause red blood cell agglutination in the fetus, leading to jaundice and anemia at birth.
• Maternal anti-Rh agglutinins can persist in the infant's blood for 1-2 months, destroying more red blood cells.
• Rapid red blood cell production by the fetal liver and spleen leads to enlargement of these organs and release of early-stage erythrocytes into circulation.
• Rh immunoglobulin (RhoGAM) is administered to Rh-negative mothers around 28-30 weeks of gestation and after delivering an Rh-positive baby to prevent sensitization to the Rh antigen.

Transfusion Reactions

• In mismatched transfusions, donor blood plasma is diluted by the recipient's blood, reducing the likelihood of agglutination of donor cells due to low agglutinin levels.
• Donor plasma agglutinins are not diluted and can react with recipient red blood cells.
• Hemoglobin released from hemolyzed red blood cells is converted into bilirubin by phagocytes and excreted in bile by the liver.
• High bilirubin concentrations can cause jaundice, typically occurring if more than 400 mL of blood is hemolyzed in less than a day.
• Acute kidney failure after transfusion reactions can be caused by toxic substances that induce renal vasoconstriction, hypotension due to red blood cell loss, and unbound hemoglobin blocking renal tubules.

Grafts

• Autografts and isografts contain the same antigens and survive normally.
• Xenografts almost always cause immune reactions and graft death within one day to five weeks unless therapy is used.
• There are 150 different antigen choices for human leukocyte antigens (HLA), resulting in over 1 trillion possible combinations.
• Except for identical twins, it's extremely rare for two individuals to have the same HLA antigens.
• Individuals with depressed immune systems can receive grafts without significant therapy.
• Allografts in individuals with healthy immune systems rarely resist rejection for more than a few weeks.
• T-cells are the primary cause of graft rejection, therefore their suppression is crucial for graft survival.
• Immunosuppressive drugs suppress T-cells or T-helper cells making individuals more susceptible to bacterial and viral infections.
• The incidence of cancer is higher in immunosuppressed individuals, possibly because the immune system normally destroys early cancer cells.

Learn about the classification of blood into types O, A, and B based on agglutinogens. Type O blood lacks A and B agglutinogens. Understand the genetic locus with three alleles and the development of anti-A and anti-B agglutinins in the absence of corresponding agglutinogens.