Antigen–Antibody Reactions, ABO blood grouping_010903.pptx

Antigen Antibody Reactions, ABO blood grouping

1. Antigen–Antibody Reactions, The ABO Blood Groups & Transfusion Reactions immunology@miu

2. objectives of lecture To know some common antigen-antibody reactions ABO blood grouping and transfusion reaction Rh Blood Type & Hemolytic Disease of the Newborn

3. introduction Reactions of antigens and antibodies are highly specific . An antibody will react only with the antigen that induced it or with a closely related antigen. Because of the great specificity, reactions between antigens and antibodies are suitable for identifying one by using the other. This is the basis of serologic reactions. However, cross reactions between related antigens can occur, and these can limit the usefulness of the test

4. Uses of Serologic (Antibody-Based) Tests

5. Most of these tests can be designed to determine the presence of either antigen or antibody To do this, one of the components, either antigen or antibody, is known and the other is unknown With a known antigen such as influenza virus , a test can determine whether antibody to the virus is present in the patient’s serum. Alternatively, with a known antibody, such as antibody to herpes simplex virus , a test can determine whether viral antigens are present in cells taken from the patient’s lesions

6. Agglutination In this test, the antigen is particulate (e.g., bacteria and red blood cells) or is an inert particle ( divalent beads) coated with an antigen. atibody, because it is divalent or multivalent, cross-links the antigenically multivalent particles and forms a latticework, and clumping (agglutination) can be seen eg. ABO blood grouping

7. Precipitation (Precipitin) In this test, the antigen is in solution . The antibody cross-links antigen molecules in variable proportions, and aggregates (precipitates) form Precipitation curve

8. In the zone of equivalence , optimal proportions of antigen and antibody combine; the maximal amount of precipitates forms, and the supernatant contains neither an excess of antibody nor an excess of antigen. In the zone of antibody excess , there is too much antibody for efficient lattice formation, and precipitation is less than maximal. In the zone of antigen excess all antibody has combined, but precipitation is reduced because many antigen–antibody complexes are too small toprecipitate (i.e., they are “soluble”)

9. In the zones of antibody excess and antigen excess, a lattice is not formed and precipitation does not occur in the equivalence zone, a lattice forms and precipitation is maximal. important application its advisable to serially dilute antibodies when performing some tests eg, in RPR titration for syphilis to avoid false negative, due zones of antibody excess

10. The ABO Blood Groups & Transfusion Reactions All human erythrocytes(RBCs) contain antigens that vary among individual members A person’s ABO blood group we have blood groups A,B, AB and O we also have rhesus blood group matching of blood group is important in the success of transplant and blood transfusion

11. The A and B genes encode enzymes that add specific sugars to the polysaccharide end on the surface of Red Blood cells H gene does not add any sugar at the end of polysccharide chain

12. Structures of the terminal sugars that determine ABO blood groups Blood group O cells have H antigen on their surface no sugars are added to the end of H antigen blood group B cells have galactosamine added to the end of the H antigen blood group A cells have N-acetylgalactosamine added to the end of the H antigen;

13. antigens on red cells

14. The plasma contains antibody against the absent antigens

15. Transfusion reactions occur when incompatible donor red blood cells are transfused e.g., if group A blood were transfused into a group B person [because anti-A antibody is present in group B] The r ed cell–antibody complex activates complement, and cause Red cells to lyse membrane attack complex are formed which lyses the red cells, causing hemolysis and anemia

16. Transfusion reaction Top panel : Red blood cells bearing A antigen are transfused into a person who is type B and therefore has antibodies to A antigen. Middle panel : Anti-A antibodies bind to A antigen on the red cells causing agglutination of red cells that can block movement of blood through capillaries causing anoxia to tissue. Bottom panel : Complement is activated by the antigen– antibody complexes and the membrane attack complex lyses the red cells, causing hemolysis and anemia

17. To avoid antigen–antibody reactions that would result in transfusion reactions, all blood for transfusions must be carefully matched erythrocytes are typed for their surface antigens by specific antibodies

18. Compatibility of Blood Transfusions Between ABO Blood Groups

19. O blood have no A or B antigens on their red cells and so are universal donors (i.e., they can give blood to people in all four groups) Note- type O blood has A and B antibodies. Therefore when type O blood is given to a person with type A, B, or AB blood, you might expect a reaction to occur . A clinically detectable reaction does not occur because the donor antibody is rapidly diluted below a significant level. ( zone of antigen excess??? ) Persons with group AB blood have neither A nor B antibody and thus are universal recipients.

20. Rhesus(Rh) blood group RBCs sometimes have another antigen on their surface called RhD antigen If you have this antigen, your blood group is RhD positive if your RBCs lack this antigen, you are RhD negative about 85% of people are RhD positive A Positive or negative sign next to blood group represent rhesus group So one can belong to any of the 8 blood groups. Blood group A RhD positive(A+), (A-), (B+), (B-), (AB+), (AB-),(O-), (O+).

21. management of incompatible blood transfusion plasma exchange therapy- to remove RBC antibodies and free haemoglobinin. this prevents acute hemolytic reaction disseminated intravascular coagulation acute kidney injury Continuous hemodiafiltration(HDF) a form of kidney replacement therapy. just like kidney dialysis helps to remove high molecular weight molecules

22. (Rhesus)Rh Blood Type & Hemolytic Disease of the Newborn About 85% of humans have erythrocytes that express the Rh(D) antigen [i.e., areRh(D)+ ]. When an Rh(D) – person is transfused with Rh(D) + blood or when an Rh(D) – woman has an Rh(D) + fetus , the Rh(D) antigen will stimulate the development of antibodies

23. Hemolytic Disease of the Newborn when the Rh(D) + erythrocytes of the fetus leak into the maternal circulation during delivery of the first Rh(D) + child IgG antibodies to Rh antigen are then produced by the mother During a second pregnancy with an Rh-positive fetus, IgG antibodies pass from the mother into the fetus via the placenta . The antibodies bind to the fetal red cells, complement is activated, and the membrane attack complex lyses the fetal red cells . Anemia and jaundice occur in the fetus/newborn.

24. As a result of the anemia, large numbers of erythroblasts are produced by the bone marrow and are seen in the blood of the newborn Subsequent Rh(D) + pregnancies are likely to be affected by the mother’s anti-D antibody , which cross the placenta to the featus, causes hemolytic disease of the newborn (erythroblastosis fetalis) often results

25. Hemolytic disease of the newborn results from the passage of maternal IgG anti-Rh(D) antibodies through the placenta to the fetus, with subsequent lysis of the fetal erythrocytes.

26. lab test The direct antiglobulin (Coombs) test is typically positive used to detect antibodie or complement proteins bound to surface of RBCs, which is causing lysis of RBCs indirect Coombs test the test detect antibodies in serum against foreign RBCs tested in prenatal testing of pregnant women also tested prior to blood transfusion

27. prevention of helolytic disease of new born in pregnant woman The problem can be prevented by administration of high-titer Rh(D) immune globulins (Rho-Gam) to an Rh(D) – mother at 28 weeks of gestation and immediately upon the delivery of an Rh(D) + child. the role of high titre anti D immuniglobulin is to destroy the baby’s RBCs that enter the mother’s immune blood stream before mother’s immune system have time to produce antibodies against them that is-they neutralise the RhD antigen from the featue, and prevent stimulating immune system of mother This prophylaxis is widely practiced and effective.

28. Case 1 a 74 year old type O Rh-poistive male was accidentally transfused with 280 mLs of type B Rh- positive red blood cells during open right hemicolectomy. Immediately after transfusion, the petient experienced hypotension followed by hemolytic reaction, disseminated intravascular coagulation and kidney injury. what condition is this case about? Explain why the patient experienced such symptoms. how can you manage the situation?

29. possible answers i. Acute Hemolytic Transfusion Reaction(AHTR) II. hypotension- mast cell mediactors are released causing vasodilation and hypotension hemolytic reaction- antibodies in recipient cells bind on donor cells. complement are activeted, RBCs are lysed, releasing Haemoglobin in circulation. disseminated intravascular coagulation(DIC)- the clotting pathway is activated causing DIC, which results in deposition of fibrin, leading to microvascular thrombi in variuos organs and contributing to multiple organ dysfuction kidney injury- due to toxicity of heme on kidney tubular cells Hameoglobin breaks down to give heme. Heme is taken up by kidney cells. in the kidney, heme-iron mediates oxidative injury(cytotoxicity) inducing cell death and promoting acute kidney injury(AKI). Heme also decreaese renal perfusion and incrases intra-tubular cast formation. intravascular clotting, hypotension and precipitationof hemoglobin in renal tubues also resuls in Acute renal Failure

30. III. management immediately discontinue the transfusion. Maintain vevous access with normsl saline. assess for breathing and circulation. Anticipate hypotension, acute renal injury(AKI) and disseminated intravascular coagulation(DIC) blood pressure support. hydration(0.9% normal saline) combined with duretics to increase urine output plasma exchange therapy- to remove RBC antibodies and free haemoglobinin. Continuous hemodiafiltration(HDF) dialysis in cases of renal failure. prompt treatment of DIC