Blood group 1

Describe and Classify different blood groups.
Define Landsteiner’s laws.

1. Blood Groups - I Ms Veena Shriram

2. Genetics of Blood Types Our blood type is established before we are BORN , by specific GENES inherited from our parents. We inherit one gene from our MOTHER and one from our FATHER. These genes determine our blood type by causing proteins called AGGLUTINOGENS to exist on the surface of all of our red blood cells.

3. Competencies - the students should achieve at the end of this topic: he should be able to Describe and Classify different blood groups. Define Landsteiner’s laws. Discuss the clinical importance of blood grouping. Describe Rh incompatibility. Describe hemolytic diseases due to Rh incompatibility. Erythroblastosis fetalis; its treatment and prevention.

4. Synopsis Introduction The ABO System Inheritance Antigens & Agglutinogens of blood groups Nature of agglutinins (Antibodies) Landstiners law Compatibility between blood groups Agglutination (Clumping) Crossmatching Possible complications of blood transfusions HDN Fate of the transfusion reactions

5. The ABO System: Discovered in 1901 by Dr. Karl Landsteiner, won Nobel prize in medicine The A & B antigens inherited as mendelian dominants 4 Main Phenotypes (A, B, AB, O) ABO gene on chromosome 9

6. Different people had different antigenic and immune properties hence blood transfusion to a person belonging to different blood group : mismatching lead to severe reactions in the body. Several hundred antigens present on the surface of RBCs. Most of these antigens do not cause major reactions, ∴ called minor blood groups e.g. MNS, P, Lutheran, Kell , Kidd, Lewis, Dufy, Diego and many others.

7. DIFFERENT BLOOD GROUP SYSTEMS ABO Rh MNS Lewis Ss P Kell system Duffy system Kidd system Lutheran (Lu) system Ii system These are mainly useful for studying inheritance of genes.

8. ABO SYSTEM: ANTIGEN : Any foreign invading substance which can evoke an immune response in the body. Antigens of blood groups are macromolecules, which occur on the surfaces of the red blood cells and on different body cells called: AGGLUTINOGENS : complex oligosaccharides present on the surface of the RBC membrane. viruses and in bacteria, too - these antigens can be determined from the third month of foetal life until the end of our lives - production of antigens are control l ed by the genes inherited from both of the parents

9. Classification of blood groups : Depending on the presence or absence of agglutinogen on the surface of RBC membrane, blood groups are classified as follows : Agglutinogen Blood Group % (Indians*) A A 41 (22) B B 09 (33) A & B AB 03 (7) - O 47 (37) * A Contribution to the Physical Anthropology & Population Genetics L.Beckman : revised by bloodBook.com 2008 .

10. Inheritance Agglutinogens are genetically determined & appear at the 6 th week of IUL. Agglutinogens A & B are inherited as Mendelian dominant characters and are formed in the presence of A & B genes (dominant). ∴ Blood group is determined by the genotype of a person i.e. the genes he has received from both parents. Genotype Blood Groups ^ AA / * AO A ^ BB / * BO B AB AB OO O ^homozygous, *heterozygous

11. Blood Group A is further classified as A 1 and A 2 (On addition of kulith extract, agglutination seen with A 1 ) In 80% people agglutinogens are present in various secretions (gastric, salivary) hence they are called secretors . ANTIBODIES: are substances formed in response to an antigen. AGGLUTININS: are specific antibodies, naturally found in the plasma ,which have the ability to bind to a specific agglutinogen e.g. antiA , antiB . They are formed in the plasma in response to various antigens entering the body via food, inhalation, bacteria etc.

12. Blood group Agglutinogen Agglutinin A A AntiB B B AntiA AB A,B --- O --- AntiA, AntiB Q: If the Ag A is present on the Red cell, why is Anti A not produced? Why is Anti B being formed in the plasma? A: Ag A is present at birth and is recognized as self antigen hence antibodies Anti A are not produced in response to antigen A entering the body. However Anti B is produced in the plasma in response to various antigens entering plasma via food, inhalation, bacteria etc. Titer of Agglutinins at different ages: At birth, concentration is zero starts at 2 to 8 months, maximum at 8 to 10yrs, declines throughout life.

13. What are blood types? http://learn.genetics.utah.edu/units/basics/blood/types.cfm There are 3 alleles or genes for blood type: A, B, & O. Since we have 2 genes, there are 6 possible combinations. Blood Types AA or AO = Type A BB or BO = Type B OO = Type O AB = Type AB

14. Genotype OO A 1 A 1 / A 1 A 2 / A 1 O A 2 A 2 / A 2 O A 1 B A 2 B BB / OB Phenotype /blood group O A 1 A 2 A 1 B A 2 B B Agglutinogen on RBC - A 1 A 2 A 1 & B A 2 & B B Agglutinin in plasma Anti-A [α] Anti-B [β] Anti-B [β] Anti-B [β] - - Anti-A [α]

15. THE DIFFERENCE BETWEEN I g M & I g G ANTIBODIES IgG IgM

16. ANTIGENS & AGGLUTINOGENS OF BLOOD GROUPS : Antigens of blood groups are macromolecules, occur on the surfaces of red blood cells & on different body cells Structures of surface – polysaccharides, glycoproteins , lipoproteins These particles of cells can be found in plants, in vertebrates, in viruses and in bacteria, too These antigens can be determined from the third month of fetal life until the end of our lives Production of antigens are controlled by the genes inherited from both of the parents At least 15 commonly occurring antigens are able to cause blood transfusion reactions

17. ANTIGENS OF O-A-B SYSTEM: The separation depends on the genetically determined polysaccharide groups of the membrane glycoproteins Two allelomorphic genes determine the O-A-B blood groups. The basic epitop (i.e. the group of antigens, which determine antigen specificity) is the H-antigen = Bld grp 0. T wo different polysaccharide rests are connected to this antigen. A & B antigen specificities are determined by th e s e polysaccharide chains. The antigens of the O-A-B systemare present in the living world – after birth in the alimentary & they produce an immune response if this baby doesn’t have this antigen. They are natural anti-A, anti-B antibodies of IgM type

18. Antigens of the ABO system An H gene codes for a fucose transferase that puts a fucose on the end of these glycolipids or glycoproteins, forming the H antigen that is usually present in individuals of all blood types. Individuals who are type A have a gene which codes for a transferase that catalyzes placement of a terminal N -acetylgalactosamine on the H antigen. Individuals who are type B have a gene which codes for a transferase that places a terminal galactose . Individuals who are type AB have both transferases. Individuals who are type O have neither, so the H antigen persists.

19. The ABO Antigens Added to Proteins or Lipids in Red Cells Substrate Molecule is H ( fucose ) A antigen is N-acetyl- galactosamine ( NAcG ) B antigen is galactose (Gal) A and B genes code for transferase enzymes

20. Antigens of the ABO system on the surface of red blood cells:

21. F G C G G F F G G G G G G G G C C H antigen A antigen B antigen C Ceramide G G G G Glucose F Fucose G Galactose G N- acetylgalactosamine

22. Subgroups of blood types A and B have been described. The most important being A 1 and A 2 . However, the difference between A 1 and A 2 appears to be quantitative; Each A 1 cell has about 1,000,000 copies of the A antigen on its surface, And each A 2 cell has about 250,000.

23. Nature of agglutinins:

24. LANDSTEINER’S LAW : States that 1 ) if an agglutinogen is present on the RBC membrane, then the corresponding agglutinin must be absent in the plasma. 2) if an agglutinogen is absent on the RBC membrane, then the corresponding agglutinin must be present in the plasma. ABO system follows both parts of Landsteiner’s law.

25. Compatibility between blood groups:   Major reaction-between Donor’s cells & recipient’s plasma  Minor reaction-Between Donor’s plasma & Recipient’s cells Donor’s group Recipient’s group A[A-β] B [B-α] AB[AB-nil ] O [ nil-αβ] A[A- β] √ χ √ χ B [B-α] χ √ √ χ AB[AB-nil] χ χ √ χ O [nil-αβ ] √ √ √ √ Blood group O - Universal Donor & Blood group AB - Universal Recipient Que: Can Blood Group A be given to AB? Ans: Yes. Since AB has no natural agglutinins, donor cells are safe and anti B of donor serum gets diluted in the recipients plasma. Que: Can Blood Group A be Given to O? Ans: No. Because donor cells (AgA ) get agglutinated by recipients anti- A.

26. AGGLUTINATION: When a specific agglutinogen e.g. AgA comes in contact with a specific agglutinin e.g. Anti A, there occurs an antigen antibody reaction in the form of agglutination . Anti A has 10 binding sites (IgM) hence potentially 10 RBC’s having agglutinogen A can bind to it. Agglutination can be between Donor RBC’s (E.g. Gr. A RBC-AgA) and Recipients plasma agglutinins (Gr. B, AntiA) or between Donor’s plasma agglutinins (Gr.A, antiB) and recipients RBC (Gr.B, AgB). Que.: Donor RBC’s having AgA are agglutinated by the recipients plasma agglutinins AntiA. What happens to recipients RBC having AgB? Do they agglutinate due to donors agglunins AntiB? Ans: No. Because the donors plasma is diluted in the recipients plasma hence the antibodies are diluted, hence fail to agglutinate the recipients RBC.

27. Red cell agglutination in incompatible plasma.

28. Crossmatching: Major Matching: Suspension of donor erythrocytes is mixed with recipient’s serum. Minor Matching: Suspension of recipient’s erythrocytes is mixed with donor’s serum In both cases if there is no agglutination, blood is perfectly compatible

29. Donor’s RBCs Recipient’s plasma Blood samples to be Serum containing typed is added to the Anti-A Anti-B drops of serum antibodies antibodies Group A Group B Group AB Group O Agglutination or clumping of RBCs Cross Matching (Major)

30. Possible complications of blood transfusions 1. Incompatibility reactions Antigens on donor’s RBC + Antibodies in recipient’s plasma RBC Agglutination Clumps I/V haemolysis release of Hb may block Haemoglobinaemia and Jaundice blood vessels Renal failure ‘DEATH’

31. 2. Fever - due to the presence of antibodies against transfused WBCs and platelets 3. Allergic reactions - asthma 4. Circulatory overload 5. Iron overload 6. Air embolism - air can go into the circulation 7. Transmission of diseases - Malaria, hepatitis B, AIDS, Syphilis To avoid these complications “ Autologous transfusion ” can be done.

32. Haemolytic disease of the newborn (HDN) * ABO Incompatibility – common but mild * Rh Incompatibility

33. Fate of the transfusion reactions: Agglutinated cells block small vessels Phagocytosis by WBC,s or they burst in the spleen or lungs leading to release of Hb Hb is then converted to bilirubin –jaundice If the titer of antibodies is very high, activation of the complement system Acute haemolysis ,released Hb blocks renal tubules -renal shutdown Determination of Blood Groups: Antiserum A Antiserum B Blood Group √ × A × √ B √ √ AB × × O

34. Thank You! 