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Immunology 2008 Lecture 12 ABO & Rh Blood Groups 21 October. ABO & Rh. OUTLINE: ABO & Rh Blood Groups Blood Transfusion ABO Immunology Genetics Rh Genetics HDN. Blood Transfusions. First transfusions in France, 1667 Banned throughout Europe in 1669
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Immunology 2008 Lecture 12 ABO & Rh Blood Groups 21 October
OUTLINE: ABO & Rh Blood Groups Blood Transfusion ABO Immunology Genetics Rh Genetics HDN
Blood Transfusions First transfusions in France, 1667 Banned throughout Europe in 1669 [Question: How to do IV injections in 1600’s?]
Blood Transfusions First transfusions in France, 1667 Banned throughout Europe in 1669 [Question: How to do IV injections in 1600’s?] ABO blood groups, Landsteiner, 1901 Transfusion became practical, but still risky Rh blood groups, Landsteiner, 1940 Transfusions became much safer
ABO Blood Groups • Landsteiner, 1909 • ● 2 antigens (A/B) • ● 4 blood “types”, A, B, AB, O (varying frequencies) • ● Isohemagglutinins, “natural antibodies”, IgM • ● Serum from type “A” agglutinates cells from“B”, • etc. (basis of “crossmatching”) • A&B are also important transplantation Ags
Failure of ABO-Incompatible Transplant Recipient was type O, heart/lung donor was type A.
ABO Antigens and Isoagglutinins BLOOD RBC SERUM TYPE ANTIGENS ANTIBODIES FREQUENCY ------------------------------------------------------------------------------ A A anti-B 40% B B anti-A 10% AB A and B none 5% O none anti-A and anti-B 45%
ABO Carbohydrates [RBC]---O- GLU - GAL | | "stem" carbohydrate NAc FUC (="H" antigen) [RBC]---O- GLU - GAL - GAL | | substance B NAc FUC [RBC]---O- GLU - GAL - GAL | | | substance A NAc FUC NAc
ABO Genotypes vs. Phenotypes Blood type Genotype (Phenotype) ------------------------------------- A/A A A/O A B/B B B/O B A/B AB O/O O
ABO Genetics A/O X B/OParents type… (A) (B) A/B A/O B/O O/OOffspring (AB) (A) (B) (O) 0.25 0.25 0.25 0.25Frequency However, cross-matching for ABO types did not guarantee the safety of transfusions…
Rh Landsteiner and Wiener, 1940: Rabbit Ab against rhesus monkey RBC reacts with some, but not all, human RBC (allelic) ● Peptide complex, multiple known antigens Major Rh antigen is encoded by D locus Rh+ (85%) vs. Rh- (15%) ●[CO2 gas channels?] ● No isoagglutinins ● IgG antibodies following sensitization
POPS1 Coomb’s Test Use hemagglutination to detect: 1) Antibody–coated RBC’s (“Direct”) 2) Anti-RBC antibody in serum (“Indirect”) Our example is for anti-Rh antibodies, but this assay may be used to detect antibodies to other RBC antigens.
Direct vs. Indirect Coomb’s Test POPS1 agglutination agglutination
Case Study Hemolytic Disease of the Newborn (HDN) [Erythroblastosis Fetalis] • 31-year old woman in her third pregnancy, she is type A, Rh-, her husband is A, Rh+ •First child was a healthy boy. • During her second pregnancy, indirect Coombs was 1:16.* • Fetus was followed closely, healthy baby girl induced at 36 wks. Current pregnancy is five years later. * At the time of birth, fetal Rh+ cells may enter the mother’s circulation and trigger an anti-Rh Ab response.
* •Indirect Coombs, @14 wks=1:8, @18 wks=1:16 •Amniotoic fluid at 22, 24, 27 and 29 wks showed increasing amounts of bilirubin. •Umbilical vein blood at 29 wks showed hematocrit of 6.2% (normal 45%) •Transfused 85ml of type O Rh- RBC. •At 30.5 wks hematocrit was 16.3%, transfuse 75 ml RBC. •Fetus examined at weekly intervals for hydrops. •At 33.5 wks hematocrit was 21%, transfused 80 ml RBC •At 34.5 wks labor was induced, normal female infant delivered. •Umbilical vein hematocrit was 29%. No further problems. [severe anemia] * Maternal anti-Rh antibodies can cross the placenta, enter the fetal circulation and cause destruction of fetal RBC’s
Why is Rh HDN relatively rare? 1) Low frequency of incompatibility (<15%) 2) Low frequency of sensitization (~15%) ● ABO incompatibility reduces risk (to ~7%) ● Non-sensitizing variants of Rh Ags 3) May have insufficient levels of Ab to cause harm Note: While Rh incompatibility is not the only cause of HDN, it is the cause of most serious cases.
To prevent Rh HDDN… RhoGam Human IgG antibody to Rh antigen D Administered to Rh- pregnant women at 28 weeks, and again within 72 hrs of birth. Reduces risk of sensitization to <1%
ABO versus Rh Maternal/Fetal Incompatibility ABO ● Common (e.g. O mother/A father) ● Mostly IgM, generally harmless ● Inhibits Rh sensitization Rh ● Uncommon (and <15% sensitization) ● IgG, more often harmful than ABO (but still relatively rare) ● Prevented with RhoGam (<1% sensitization)
Variety of Blood Product Transfusions • Whole blood • Packed RBC • Leukocyte-Depleted • RBC • Washed RBC • Buffy Coat • Platelets • Plasma • Fractionated Plasma • Albumin • Immunoglobulin • Clotting Factors May variously contain: • live leukocytes (GvH) • serum proteins (serum sickness, allergy) • infectious agents
WEDNESDAY Clinical Correlate #1, Dr. Gupta: Monoclonal Gammopathies FRIDAY Inbreeding, Appendix 8 MHC & Transplantation, Chapter 11 MONDAY Exam 1, 9:00 AM, (Covers all material through Friday) Cell Interactions in CMI I, Chapter 12 (A9)