It was stated that Rh antigens are so sparsely scattered in the red cell surface that IgG molecules bound to the Rh antigens are too far apart to fix C1q.Therefore, complement-mediated hemolysis cannot be invoked to explain hemolytic disease of the newborn. By what mechanism are the red cells destroyed? 248Case 44: Hemolytic Disease of the NewbornFig. 44.1 Hemagglutination is usedto type blood and match compatibledonors and recipients for bloodtransfusion. Common gut bacteria bearantigens that are similar or identical toblood group antigens, and these stimulatethe formation of antibodies againstthese antigens in individuals who do notbear the corresponding antigen on theirown red blood cells (left column); thus,type O individuals, who lack A and Bantigens, have both anti-A and anti-Bantibodies, whereas type AB individualshave neither. The pattern of agglutinationof the red blood cells of a transfusiondonor or recipient with anti-A and anti-Bantibodies reveals the individual's ABOblood group. Before transfusion, theserum of the recipient is also tested forantibodies that agglutinate the red bloodcells of the donor, and vice versa, aprocedure called a cross-match, whichmay detect potentially harmful antibodiesagainst other blood groups that are notpart of the ABO system.30.5 weeks: hematocrit up to16.3% Further transfusionrequested.Serum fromindividuals of typeAnti-A and anti-BantibodiesAnti-B antibodiesBAnti-A antibodiesABNo antibodiesagainst A or BR-GlcNAc-GalFueno agglutinationno agglutinationno agglutinationno agglutinationRed blood cells from individuals of typeExpress the carbohydrate structuresR-GlcNAc-Gal-GalNAc R-GlcNAc-Gal-GalFúcRicagglutinationno agglutinationagglutinationno agglutinationagglutinationagglutinationno agglutinationno agglutinationR-GlcNAc-Gal-GaNAC3-2.3-2R-GNA-Gal-Galagglutinationagglutinationagglutinationno agglutinationThe Rh antigenic determinants are spaced very far apart on the red cell surface. Asa consequence, IgG antibodies against the Rh antigen do not fix complement andtherefore do not hemolyze red blood cells in vitro. For reasons that are less wellunderstood, IgG antibodies against the Rh antigen do not agglutinate Rh-positivered blood cells. Because of this it was very difficult to detect Rh antibodies untilRobin Coombs at the University of Cambridge devised a solution to the prob-lem by developing antibodies against human immunoglobulin. He showed thatRh-positive red blood cells coated with IgG anti-Rh antibodies could be taken froma fetus and agglutinated by antibodies against IgG. Furthermore, he showed thatwhen the serum of an alloimmunized woman was incubated with Rh-positive redblood cells, these red blood cells could then be agglutinated by antibody againstIgG (Fig. 44.2). The former is called the direct Coombs test and the latter the indi-rect Coombs test. This application of immunology to a vexing clinical problem ledultimately to treatment and prevention of the problem.The case of Cynthia Waymarsh: a fetus inimmunological distress.Mrs Waymarsh was 31 years old when she became pregnant for the third time. Shewas known to have blood group A, Rh-negative red cells. Her husband was alsotype A but Rh-positive. Their first-born child, a male, was healthy. During her secondpregnancy Mrs Waymarsh was noted to have an indirect Coombs titer at a 1:16 dilu-tion of her serum. The fetus was followed closely, and the delivery of a healthy babygirl was induced at 36 weeks of gestation.Five years later, Mrs Waymarsh became pregnant again. At 14 weeks of gestationher indirect Coombs titer was 1:8, and at 18 weeks it was 1:16. Amniotic fluid wasobtained at 22, 24, 27, and 29 weeks of gestation and was found to have increasing CASE 44HEMOLYTIC DISEASEOF THE NEWBORNThe adaptive immune responsedistinguishes genetic differences betweenindividuals of the same species.Adaptive immune responses evolved to protect vertebrate species against the worldof microorganisms. However, anything discerned as 'nonself' may become a targetof such responses, which can include molecular differences between individualswithin a species. An antigenic determinant present in some members of a speciesbut not in others is said to show polymorphic variation, and antibodies directedagainst such determinants are called alloantibodies. Perhaps the best-knownalloantibodies are those that are used to determine our blood groups. Individualswho have red cells of type A have alloantibodies that react with the red blood cellsof individuals who are type B and vice versa. Individuals who have red blood cellsof type AB have no alloantibodies, and those with type O red blood cells have anti-bodies against both A and B red blood cells (Fig. 44.1). These alloantibodies arisebecause the capsules of Gram-negative bacteria, which inhabit our gut, bear anti-gens that stimulate antibodies that cross-react with the carbohydrate antigens ofthe ABO blood groups.Alloantibodies induced by a fetus in the pregnant mother frequently cause seriousproblems. Alloimmunization most often results from Rhesus (Rh) incompatibilitybetween mother and fetus. Approximately 15% of women are Rh-negative; that is,their red blood cells do not bear the Rh antigen. A woman who is Rh-negative hasan 85% chance of marrying an Rh-positive man, and their chances of having anRh-positive baby are very high. Not infrequently, during delivery of the newborninfant, some blood escapes from the fetal circulation into the maternal circulation,and as a result of this, the mother develops alloantibodies against the Rh antigen.During a subsequent pregnancy with an Rh-positive fetus, the maternal IgG alloan-tibodies cross the placenta and cause destruction of the fetal red cells, causing ane-mia. As we shall see, the consequences of this can be very serious and result in fetaldeath or severe damage to the newborn infant.TOPICS BEARINGON THIS CASE:Antibodysuppression ofB-cell activationABO blood groupsAlloantibodiesRhesus blood groupCoombs testHemagglutinationassays

IgG is the most prevalent form of antibody found in circulation, accounting for around 75% of serum…

Answered: t was stated that Rh antigens are so…

11th Edition

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Author:Elaine N. Marieb, Katja N. Hoehn

Publisher:Elaine N. Marieb, Katja N. Hoehn

Chapter1: The Human Body: An Orientation

Section: Chapter Questions

Problem 1RQ: The correct sequence of levels forming the structural hierarchy is A. (a) organ, organ system,...