Blood Groups and Transfusion

Question	Answer
Who proposed the ABO blood grouping system?	Landsteiner.
How was the ABO blood grouping system tested?	Landsteiner took blood from 6 colleagues and allowed it to clot. He then used the serum, which contained no clotting factors because the blood had been allowed to clot, against the erythrocytes of other samples. There was either agglutination or no agglutination, so Landsteiner proposed that there were two antigens, A and B, and cells that did not agglutinate must lack these antigens - group O.
Human erythrocyte membranes contain antigenic proteins and glycoproteins, but what do they lack that nucleated cells possess (besides the obvious)?	The major histocompatibility complex proteins for recognising foreign tissues, that are found on nucleated cells.
What are two main factors that are the major cause of a rejection reaction after a blood transfusion?	The ABO antigens and the Rhesus (Rh) antigens.
In early life, perhaps before 3 months of age, antibodies are produced that are present in the plasma. The only antibodies produced are against antigens that your erythrocytes do NOT possess. What is this antibody production suggested to be a response to?	Bacterial antigens or food antigens in the gut.
If a person is blood type O, what antigens do they have on their erythrocytes and what antibodies do they have in their plasma?	Individuals of blood group O have no A or B antigens on their erythrocytes and thus have anti-A and anti-B antibodies in their plasma.
If an individual is blood group A, what antigens do they have on their erythrocytes and what antibodies are present in their plasma?	In individuals with blood group A, A antigens are present on their erythrocytes and anti-B antibodies are present in their plasma.
If an individual is ABO blood group B, what antigens are present on their erythrocytes and what antibodies are present in their plasma?	In an ABO blood group B individual, the erythrocytes possess B antigens and the plasma contains anti-A antibodies.
If an individual is ABO blood group AB, what antigens do their erythrocytes possess and what antibodies does their plasma contain?	In an AB individual, both A and B antigens are present on the erythrocytes and so no antibodies are present in the plasma.
Where might antigens be present on a membrane?	Some are expressed directly as membrane proteins, as with the Rhesus factor antigens, whereas others are carbohydrates attached to membrane protein or lipid groups.
What is responsible for blood group incompatibility?	Blood group antigens.
The A and B antigens of the ABO blood grouping system are added on to a universal structure - the H antigen, which is all that blood group O individuals express on their erythrocytes. What four components make up the H antigen?	Galactose, fucose, n-acetylglucosamine, and a lipid or protein 'tail'.
What is the A antigen carbohydrate?	N-acetylgalactosamine
What is the B antigen carbohydrate?	D-galactose
In an AB individual, in what order are the carbohydrates expressed on the antigen?	Randomly.
What is necessary for A or B antigens to be expressed?	The related genes to be present and active.
What is Landsteiner's law?	The presence of antigen on the cell implies the absence of the corresponding antibody in the serum, and the presence of the opposite antibody (or none).
What are immunoglobulins?	Serum antibodies.
What are the five types of immunoglobulin?	IgA, IgD, IgE, IgG and IgM
What approxiate proportion of serum immunoglobulin does IgM comprise?	10%
What are the heavy chains of IgM?	µ chains
Why is the production of IgM a primary immune response?	Because IgM is pentameric and so the larger structure means it has a greater chance of matching an antigen.
Which immunoglobulin is naturally present against antigens A and B?	IgM
What approximate proportion of serum immunoglobulin does IgG comprise?	~75%
What type of chains are the heavy chains of IgG?	γ (gamma) chains
Why is the production of IgG a secondary immune response?	Because its production requires a stimulus, such as the presence of a foreign body or erythrocyte.
An antibody is Y-shaped. Where are the two identical binding sites for its antigen?	On each 'arm' of the Y.
An antibody is composed of 4 polypeptide chains. What are these and what holds them together?	Two identical heavy and two smaller, light chains, which are held together by disulphide bonds.
How is the antigen-binding site of an antibody formed?	By the close proximity of a heavy chain variable domain (Vh) and a light chain variable domain (Vl).
Which parts of the antibody differ most in their sequence and structure between antibodies?	The heavy chain variable domain and light chain variable domain.
Erythrocytes are biconcave discoid in shape. They can approach each other in isotonic solution as close as 7.9nm (spherical face) or 10.3nm (concave face). What is this governed by?	Repulsive forces, the 'net negative charge' or 'zeta potential'.
What is the agglutination reaction?	Antibodies can bind to antigens on erythrocyte membranes using their antigen binding sites, and the fact that each antibody can bind to more than one antigen means that they aggregate, or agglutinate. The pentameric nature of IgM and its size means that it can bind to up to 10 antigens and bridge gaps of around 30nm.
What would you test to identify an individual's ABO blood group?	You would test both erythrocytes and serum.
What is the forward aspect of the agglutination reaction?	Testing an individual's erythrocytes by adding different antibodies to them.
What is the reverse aspect of the agglutination reaction?	Testing an individual's serum antibodies by adding different erythrocytes.
What should be true of the forward and reverse aspects of an ABO blood grouping test?	They should be the inverse of one another.
Describe the dominant nature of the ABO genes inherited from our parents.	Both A and B genes are dominant, whereas O is recessive. The possible genotypes are therefore A, B, AB, AO, BO, and OO. The possible genotypes are A, B, AB and O.
How did Landsteiner and Weiner discover the Rhesus factor?	By injecting the erythrocytes of a Rhesus monkey into a rabbit, which consequently produced antibodies, and these antibodies would agglutinate 85% of human Caucasian erythrocytes but not the remaining 15%.
A similar antibody to the Rhesus factor was found in which humans?	Those who had just had a blood transfusion and in mothers who had given birth to a baby with haemolytic disease of the newborn.
What is erythroblastosis fetalis?	Erythroblastosis fetalis, or haemolytic disease of the newborn, occurs in a woman's second pregnancy when, in her first, she and her baby had different Rh groups. Microbleeds across the placenta, or blood exchange during delivery, causes the mother's Rh-specific B cell to become activated and remove the foreign body as well as creating a memory cell. In the second pregnancy, maternal IgG antibodies cross the placenta and attack the foetus' erythrocytes, causing them to become spherical and leaky.
What is kernicterus?	Kernicterus occurs when a foetus has erythroblastosis fetalis and the spherical, leaky erythrocytes leak bilirubin. The pigment accumulates and if it accumulates in the brain and nervous tissue, it causes yellow staining and tissue damage - this is kernicterus.
What is the correct term for erythrocyte destruction?	Erythroid hyperplasia.
How can erythroblastosis fetalis be prevented?	By treating the mother with prophylactic rhogam, a chemical which prevents B cell activation and memory cell formation.
What are the 3 pairs of genes within the Rhesus group?	C and c, D and d, and E and e. (These are either/or not dominant/recessive)
Which antigen do people originally labelled 'Rhesus positive' have on the surface of their erythrocytes?	D.
What is the Rhesus group determined by?	A single point mutation.
Which groups of people is the Rh d antigen present and not present?	The Rh d antigen is absent in Rhesus negative Caucasian individuals, but in black populations there is a large duplication which causes it to be reactive.
Which blood type makes up 44% of the UK population, with 37% being Rhesus positive and 7% being Rhesus negative?	O.
Which blood group makes up 42% of the population, with 35% being Rhesus positive and 7% being Rhesus negative?	A.
Which blood group makes up 10% of the UK population, with 8% being Rhesus positive and 2% being Rhesus negative?	B.
Which blood group is the rarest in the UK population, constituting only 4% of people, with 3% of these being Rhesus positive and 1% being Rhesus negative?	AB.
Genes in populations differ geographically. Where in the world are there populations of entirely ABO blood group O people?	South America.
Antibodies to ABO antigens are present in everybody, except..?	AB individuals.
ABO antigens are present in humans without what?	Prior sensitisation.
What is causes when a person undergoes a mismatching blood transfusion?	An immunological reaction.
What happens when a person undergoes a mismatching blood transfusion?	The antibody present in the person's serum binds to the foreign antigen and activates the complement system. This results in the production of membrane attack complexes that cause the transfused cells to swell and leak haemoglobin. Free haemoglobin released into the plasma can cause acute renal failure, as the kidneys try to filter large molecules from the blood. This leads to fever, pain, circulatory collapse, haemorrhage, and even death.
The immunological reaction that results from a mismatched blood transfusion can result from how low an amount of blood?	Even below 50ml.
Which blood group is universally accepted by people's immune systems but relatively rare in the UK (7%) and kept for emergencies?	ABO blood group O.
Antibodies to Rh antigens are only present following prior sensitisation. What forms might this sensitisation take?	A previous blood transfusion or pregnancy with a baby that has a different Rhesus group from the mother.
Why can Rh positive ABO group-matched blood be given to Rh negative men once in an emergency?	Because they will develop antibodies to it but still receive the benefits of the transfusion, without there being a risk of these antibodies one day attacking a foetus' erythrocytes, as there is in women. It is for this reason that Rhesus negative blood, which is relatively rare, is kept for Rhesus negative children and women of child-bearing age.
List three blood grouping systems other than the ABO and Rhesus systems, and the antigens they involve.	The Kell (antigen K), Duffy (antigen Fya) and Kidd (antigen Jka) systems.
What makes an antigen a 'poor antigen'?	Being less likely to cause an immunological reaction - such as the Kell, Duffy and Kidd blood antigens which are between 10-1000 times less likely to cause an immunological reaction and antibody production than the D (Rh) antigen.
What are the most frequent causes of giving incompatible blood?	Incorrect labelling of samples and confusion between recipients with the same name.
What is cross-matching of blood?	The mixing of patient and donor blood. The ABO and Rh groups should already have been matched, but this checks for any other potentially clashing antigens and transfusion should only go ahead if there is no agglutination.
What is the purpose of cross-matching blood?	To ensure that there are no antibodies present in the recipient's plasma that will react with the donor's cells in a transfusion.

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