The Blood Group System s

1. The Blood Group Systems Efrida Maret 2011

2. Basic Immunohematology Concept Immunohematology: Serologic, genetic, biochemical, and molecular study of antigens associated with membrane structures on the cellular constituents of the blood, and immunologic properties & reactions, of all blood components and constituents.

3. History Karl Landsteiner (1900) golongan darah 26 sistem golongan darah Paling penting: ABO Rhesus

4. History of Blood Groups and Blood Transfusions • Experiments with blood transfusions have been carried out for hundreds of years. Many patients have died and it was not until 1901, when the Austrian Karl Landsteiner discovered human blood groups, that blood transfusions became safer. • He found that mixing blood from two individuals can lead to blood clumping. The clumped RBCs can crack and cause toxic reactions. This can be fatal. http://nobelprize.org/medicine/educational/landsteiner/readmore.html

5. History of Blood Groups and Blood Transfusions (Cont.) • Karl Landsteiner discovered that blood clumping was an immunological reaction which occurs when the receiver of a blood transfusion has antibodies against the donor blood cells. • Karl Landsteiner's work made it possible to determine blood types and thus paved the way for blood transfusions to be carried out safely. For this discovery he was awarded the Nobel Prize in Physiology or Medicine in 1930.

6. What is blood made up of? An adult human has about 4–6 liters of blood circulating in the body. Blood consists of several types of cells floating around in a fluid called plasma.The red blood cells (RBCs) contain haemoglobin, a protein that binds oxygen. RBCs transport oxygen to, and remove carbon dioxide from the tissues.The white blood cells fight infection.The platelets help the blood to clot, if you get a wound for example.The plasma contains salts and various kinds of proteins.

7. Erythrocytes • Structure • Biconcave, anucleate • Components • Hemoglobin • Lipids, ATP, carbonic anhydrase • Function • Transport oxygen from lungs to tissues and carbon dioxide from tissues to lungs

8. Blood Grouping • Determined by antigens (agglutinogens) on surface of RBCs • Antibodies (agglutinins) can bind to RBC antigens, resulting in agglutination (clumping) or hemolysis (rupture) of RBCs • Groups • ABO and Rh

9. Erythrocyte Antigens & Antibodies • > 700 antigens  organized into 29 blood group systems by the International Society of Blood Transfusion (ISBT).

10. ABO Antigens • Also express in many tissues, body fluids, platelet and endothel). • Most important blood group system in transfusion and organ transplantation. • 3 antigens: A, B, H (biosynthetic precursor of A & B antigens). • 4 phenotypes: group A, B, AB, O • A & B: autosomal codominant antigens  expressed on group A, B & AB RBC

12. Null and Weak Phenotypes • ABO antigens can: • Weakened  weak A, weak B phenotypes • Anomalous: • Inherited: cis-AB • Acquired: • Absence (Null phenotype): • Classic Bombay  completely absence of all ABH antigens on RBC surface • Para-Bombay  shows little/no antigen in RBC but normal in secretion/body fluids.

13. ABO antigen Biochemistry • Carbohydrate • ABH antigens expressed on RBC glycoproteins & glycosphingolipid (type 2,3,4 chain)  RBC origin. Type 1 chain are synthesized by gastrointestinal mucosa  secreted into plasma  passively adsorbed onto RBC membrane

15. ABO Antibodies • Weak or absent in newborn  3-6 mo • 5-10 yo  adult level • Advancing age  slight decrease • Detected at room temperature, saline agglutinins with optimal reactivity at 40C. • Mostly IgM. • IgG (reactive at 370C) can occur after transfusion/pregnancy; higher titer; less readily neutralized by soluble blood group substances. • Can fix complement  hemolysis in vivo/vitro • Can cause: hemolytic transfusion reaction & hemolytic disease of the new born.

17. Perkembangan antigen-antigen A dan B sel darah merah • Perkembangan antigen eritrosit sejak janin s/d remaja. • Bayi baru lahir (s/d 3 bulan) : reaksi lebih lemah dibanding dewasa, terutama antibodi • Jadi pengujian pada BBL  cukup eritrosit saja

18. Less common ABO antibodies • Anti-A1 • Anti-H

19. Blood Groups, Blood Typing and Blood Transfusions The discovery of blood groups Experiments with blood transfusions, the transfer of blood or blood components into a person's blood stream, have been carried out for hundreds of years. Many patients have died and it was not until 1901, when the Austrian Karl Landsteiner discovered human blood groups, that blood transfusions became safer. Mixing blood from two individuals can lead to blood clumping or agglutination. The clumped red cells can crack and cause toxic reactions. This can have fatal consequences. Karl Landsteiner discovered that blood clumping was an immunological reaction which occurs when the receiver of a blood transfusion has antibodies against the donor blood cells.Karl Landsteiner's work made it possible to determine blood types and thus paved the way for blood transfusions to be carried out safely. For this discovery he was awarded the Nobel Prize in Physiology or Medicine in 1930. Blood group 0If you belong to the blood group 0 (null), you have neither A or B antigens on the surface of your red blood cells but you have both A and B antibodies in your blood plasma. What are the different blood groups? • The differences in human blood are due to the presence or absence of certain protein molecules called antigens and antibodies. • The antigens are located on the surface of the RBCs and the antibodies are in the blood plasma. • Individuals have different types and combinations of these molecules.   • The blood group you belong to depends on what you have inherited from your parents.

20. What are the different blood groups? • There are more than 20 genetically determined blood group systems known today • The AB0 and Rhesus (Rh) systems are the most important ones used for blood transfusions. • Not all blood groups are compatible with each other. Mixing incompatible blood groups leads to blood clumping or agglutination, which is dangerous for individuals.

21. ABO blood grouping system According to the ABO blood typing system there are four different kinds of blood types: A, B, AB or O (null).

22. Blood group AIf you belong to the blood group A, you have A antigens on the surface of your RBCs and B antibodies in your blood plasma. Blood group BIf you belong to the blood group B, you have B antigens on the surface of your RBCs and A antibodies in your blood plasma. AB0 blood grouping system

23. Blood group O If you belong to the blood group O (null), you have neither A or B antigens on the surface of your RBCs but you have both A and B antibodies in your blood plasma. Blood Groups, Blood Typing and Blood Transfusions The discovery of blood groups Experiments with blood transfusions, the transfer of blood or blood components into a person's blood stream, have been carried out for hundreds of years. Many patients have died and it was not until 1901, when the Austrian Karl Landsteiner discovered human blood groups, that blood transfusions became safer. Mixing blood from two individuals can lead to blood clumping or agglutination. The clumped red cells can crack and cause toxic reactions. This can have fatal consequences. Karl Landsteiner discovered that blood clumping was an immunological reaction which occurs when the receiver of a blood transfusion has antibodies against the donor blood cells.Karl Landsteiner's work made it possible to determine blood types and thus paved the way for blood transfusions to be carried out safely. For this discovery he was awarded the Nobel Prize in Physiology or Medicine in 1930. What is blood made up of? An adult human has about 4–6 liters of blood circulating in the body. Among other things, blood transports oxygen to various parts of the body. Blood consists of several types of cells floating around in a fluid called plasma.The red blood cells contain hemoglobin, a protein that binds oxygen. Red blood cells transport oxygen to, and remove carbon dioxide from, the body tissues.The white blood cells fight infection.The platelets help the blood to clot, if you get a wound for example.The plasma contains salts and various kinds of proteins. What are the different blood groups? The differences in human blood are due to the presence or absence of certain protein molecules called antigens and antibodies. The antigens are located on the surface of the red blood cells and the antibodies are in the blood plasma. Individuals have different types and combinations of these molecules. The blood group you belong to depends on what you have inherited from your parents. There are more than 20 genetically determined blood group systems known today, but the AB0 and Rh systems are the most important ones used for blood transfusions. Not all blood groups are compatible with each other. Mixing incompatible blood groups leads to blood clumping or agglutination, which is dangerous or individuals. Nobel Laureate Karl Landsteiner was involved in the discovery of both the AB0 and Rh blood groups. AB0 blood grouping system Blood group AB If you belong to the blood group AB, you have both A and B antigens on the surface of your RBCs and no A or B antibodies at all in your blood plasma.

24. Why do individuals produce antibodies to antigens they do not have? • The "A“ and "B" antigens are also produced by some other plants and microorganisms. Thus, individuals who do not recognize one or more of these antigens as "self" will produce antibodies against the plant or microbial antigens. • These antibodies will also react with human antigens of the same kind whether introduced via a blood transfusion or a tissue graft.

25. ABO inheritance and genetics • The ABO gene is autosomal (the gene is not on either sex chromosomes) • The ABO gene locusis located on the chromosome 9. • A and B blood groups are dominant over the O blood group • A and B group genesareco-dominant • Each person has two copies of genes coding for their ABO blood group (one maternal and one paternal in origin)

26. AUTOSOMAL CHROMOSOME The alleles for Blood group are in the same place on the chromosome 9. However the genes have a different code giving the different blood group A B Mustafa Sara one alleles from Mustafa and one from Sara.

27. What do co-dominant genes mean? This meant that if a person inherited one A group gene and one B group gene their red cells would possess both the A and B blood group antigens. These alleles were termed A ( which produced the A antigen ), B (which produced the B antigen) and O (which was "non functional"and produced no A or B antigen)

28. Possible Blood group Genotypes

29. Possible Blood group Genotypes

30. Blood Group Antigens on RBCs Antibodies in Serum Genotypes A A Anti-B AA or AO B B Anti-A BB or BO AB A and B Neither AB O Neither Anti-A and anti-B OO • The ABO blood groups • The most important in assuring a safe blood transfusion. • The table shows the four ABO phenotypes ("blood groups") present in the human population and the genotypes that give rise to them.

31. Why group A blood must never be given to a group B person? • Giving someone blood from the wrong ABO group could be fatal. • The anti-A antibodies in group B attack group A cells and vice versa. • Blood group O negative is a different story.

32. The Rhesus (Rh) System

33. Golongan Darah Rhesus • Ciri-ciri antigennya mirip dengan sistem ABO • Dapat menyebabkan reaksi ketidak -cocokan pada transfusi atau kehamilan

34. The Rh(D) Antigen • RH is the most complex system, with over 45 antigens • Discovered in 1940 after work on Rhesus monkeys • Subsequently discovered to be unrelated to monkeys • RH gene located on short arm of chromosome 1 ABO & Rh(D)

35. Simple Genetics of Rh(D) • 86% of caucasians are Rh(D) pos • The antithetical antigen d has not been found • The d gene is recessive: • Dd, dD, DD, persons are Rh(D) pos • Only dd persons are Rh(D) neg ABO & Rh(D)

36. Distribution of Rh(D) Types ABO & Rh(D)

37. Significance of Rh(D) • 80% of Rh(D) neg persons exposed to Rh(D) pos blood will develop anti-D • Anti-D can also be stimulated by pregnancy with an Rh(D) positive baby • Sensitisation can be prevented by the use of anti-D immunoglobulin, antenatally and post natally • Rh(D) neg females of childbearing potential should never be given Rh(D) positive blood products ABO & Rh(D)

38. Inheritance • ABO & RH genes are not linked • ABO & Rh(D) type are inherited independently For example: An A Rh(D) pos mother and a B Rh(D) pos father could have an O Rh(D) neg child ABO & Rh(D)

39. Inheritance of ABO and Rh(D) Mother Group A AO Rh(D) pos Dd Father Group B BO Rh(D) pos Dd Group A AO Rh(D) pos Dd Group B BO Rh(D) pos Dd Group O OO Rh(D) neg dd ABO & Rh(D)

40. The Rhesus (Rh) System Well, it gets more complicated here, because there's another antigen to be considered - the Rh antigen.Some of us have it, some of us don't. If it is present, the blood is RhD positive, if not it's RhD negative. So, for example, some people in group A will have it, and will therefore be classed as A+ (or A positive). While the ones that don't, are A- (or A negative). And so it goes for groups B, AB and O.

41. The Rhesus (Rh) System (Cont.) • Rh antigens are transmembrane proteins with loops exposed at the surface of red blood cells. • They appear to be used for the transport of carbon dioxide and/or ammonia across the plasma membrane. • They are named for the rhesus monkey in which they were first discovered. • RBCs that are "Rh positive" express the antigen designated D. • 85% of the population is RhD positive, the other 15% of the population is running around with RhD negative blood.

42. BloodType A person with Rh- blood does not have Rh antibodies naturally in the blood plasma Genotype AllelesProduced Rh positive RR R Rr R or r Rh negative rr r Rh Blood Group and Rh Incompatibility

43. Do you know which blood group you belong to? According to above blood grouping systems, you can belong to either of following 8 blood groups:

44. A person with Rh- blood can develop Rh antibodies in the blood plasma if he or she receives blood from a person with Rh+ blood, whose Rh antigens can trigger the production of Rh antibodies. • A person with Rh+ blood can receive blood from a person with Rh- blood without any problems.

45. Why is an Rh incompatibility so dangerous when ABO incompatibility is not during pregnancy? • Most anti-A or anti-B antibodies are of the IgM class (large molecules) and these do not cross the placenta. • In fact, an Rh−/type O mother carrying an Rh+/type A, B, or AB foetus is resistant to sensitisation to the Rh antigen. • Her anti-A and anti-B antibodies destroy any foetal cells that enter her blood before they can elicit anti-Rh antibodies in her.

46. Rh incompatibility during pregnancy (cont.) • This phenomenon has led to an effective preventive measure to avoid Rh sensitisation. • Shortly after each birth of an Rh+ baby, the mother is given an injection of anti-Rh antibodies (or Rhogam). • These passively acquired antibodies destroy any foetal cells that got into her circulation before they can elicit an active immune response in her.

47. Any questions?