Rhesus and Other blood groups- amanda

Question 1

When was Rhesus blood group first mentioned?

Answer 1

1939
Levine and Stetson described a mother who gave birth to still born child and despite being ABO compatible with her husbands suffered a transfusion reaction when transfused his blood

Question 2

Who discovered another blood type Rh factor- antigens that is either present or absent indicated with a + or -

Answer 2

Landsteiner and Wiener in 1940

Question 3

How was the antigen discovered?

Answer 3

Discovered in blood of Rhesus monkey whilst doing an experiment with red cells from the monkey which were transfused to rabbits and other rodents

Question 4

What did they also discover in blood of Rhesus monkey

Answer 4

Not only did the antibody in the rodents serum agglutinate the Rhesus monkey red cells, it also agglutinated the red cells of 85% of the human population.

Question 5

Rh antigen

Answer 5

Another surface protein that is found on the surface of red blood cells .
An individual either has the Rh factor on RBC + or doesn’t - , genetically determined
- individuals who are Rh- will produce antibodies that attack Rh+ cells
- particularly dangerous if a mother is Rh- and her foetus is Rh+

Question 6

If a person has both A and Rh antigens what is there blood group?

Answer 6

A+

Question 7

True or False: People that are Rh negative do not produce antibodies against Rh antigen unless they are exposed to the antigen

Answer 7

True

Question 8

Who identified an antibody reacting against blood donors with the same frequency as anti-Rh in transfusion recipients

Answer 8

Weiner and Peters

Question 9

Blood Group RH system

Answer 9

• comprises some 56 antigens (61 previously described but 5 now obsolete)
• first antigen=RhD.

Question 10

Phenotype is RhD positive/negative

Answer 10

Genotype- RHD

Question 11

When is somebody said to have the Rhesus factor on their red cells (I.e. RhD positive)

Answer 11

When an individuals red cells are agglutinated by antiserum containing anti-D

Question 12

Somebody lacks the Rhesus factor (I.e., RhD negative)

Answer 12

When an individuals cells are not agglutinated by the antiserum containing anti-D

Question 13

What is multipass antigen thought to be involved in?

Answer 13

Maintaining structural integrity as well as transporting ammonium or carbon dioxide for exchange in the liver or kidney where RH associated antigens reside

Question 14

What do Rh Null cells form

Answer 14

Stomatocytes with reduced lifespan due to association with intergrin associated protein CD47

Question 15

What proteins are present in the kidney, liver, brain, and skin where ammonia production and elimination occur?

Answer 15

Non erythrocytes Rh glycoproteins RHBG and RhCG

Question 16

What are the functions of the RH system proteins?

Answer 16

• Integrity of the red blood cell structure
• Ammonium transport

Question 17

What is the most immunogenic and the first antigen of the Rhesus system?

Answer 17

RhD

Question 18

What are the Rhesus antigens most frequently referred to?

Answer 18

Rh- D. -C, -E, -c, -e

Question 19

True or false- there is no Rh-d antigen

Answer 19

True.
D negative denotes absence of RhD antigen

Question 20

Percentages of RhD positive in populations

Answer 20

82-85% Caucasians
95% black Africans
100% Far East

Question 21

When is the RhD antigen developed?

Answer 21

Early gestational period

Question 22

RHD gene

Answer 22

Produces D antigens

Question 23

RHCE gene

Answer 23

Produces Cc and Ee antigens

Question 24

Are Rh antibodies mostly immune antibodies

Answer 24

Yes

Question 25

What is responsible for most clinical problems

Answer 25

Anti-D Used to identify RhD positive and negative individuals

Question 26

Are rhesus antibodies usually naturally occurring?

Answer 26

No

Question 27

Can anti-D antibodies develop in a RhD negative person who is exposed to blood from an RhD positive individual ?

Answer 27

Yes

Question 28

What are the two mechanisms of sensitisation ?

Answer 28

- incompatible transfusions - pregnancy

Question 29

Why is the RH system so important?

Answer 29

- severe haemolytic transfusion reactions - haemolytic disease of the newborn : 50% of all pregnant women who make antibodies make antibody specificities to one of the antigens of the Rh system - Implicated as autoantibody specificity in cases of Warm Autoimmune haemolytic anaemia

Question 30

When was the Kell Blood group system discovered?

Answer 30

1946

Question 31

What is the estimation of individuals who are Kell negative when exposed to Kell positive red cell will make anti-K

Answer 31

Approximately 1:20

Question 32

How many Kell antigens have been discovered

Answer 32

37

Question 33

What is the K antigen of prime importance in transfusion medicine and HDN?

Answer 33

Original K antigen

Question 34

Where is the Kel gene located?

Answer 34

Chromosome 7, with 19 coding sequences (exons)

Question 35

What is the Kell glycoprotein also known as?

Answer 35

CD238 GENE FOR Xk coded on X chromosome

Question 36

KEL2, KEL4, KEL7

Answer 36

High incidence in all populations

Question 37

KEL3

Answer 37

2% of Caucasians but not present in Africans or Japanese

Question 38

KEL1

Answer 38

9% Northern Europeans, 1.5% African descent, Rare In east asia

Question 39

KEL10

Answer 39

Only found in Finns and Japanese

Question 40

KEL6

Answer 40

Confined to African populations, frequency of 16%

Question 41

McLeod Syndrome

Answer 41

- Reduction or absence of Kell glycoprotein and Kx - very rare X linked condition so almost exclusively found in boys - associated with acanothocytes, reduced red cell survival, and reticulocytosis - muscular and neurological defects may also be observed - McLeod syndrome occasionally associated with X linked disorder of chronic granulomatous disease (CGD)

Question 42

CGD

Answer 42

Associated with defective phagocytic cell kill mechanism whereby microorganisms engulfed but not killed by phagocytes, patients susceptible to infection

Question 43

What does CGD arise from

Answer 43

Deletion of X chromosome material which spans both loci. Caused by mutations in any one of four genes that encode the subunits of phagocyte NADPH oxidase, the enzyme that generates microbicidal (and pro-inflammatory) oxygen radicals.

Question 44

NADPH oxidase

Answer 44

Enzyme that generates microcidal oxygen radicals

Question 45

Kell Antibody characteristics

Answer 45

- IgG immune antibodies detectable by LISS AGT test - Implicated in transfusion reactions - HDN- well developed at an early stage of foetal development -associated with reduced reticulocytosis and erythroblastosis - not associated with hyperbilirubinaemia - specificities with AIHA

Question 46

Kell antibodies

Answer 46

- reactive at 37 degrees Celsius in AHG test, protease treatment of red cells does not effect Kell antigens - detectable in papain tests

Question 47

What else is Kell antibodies implicated in?

Answer 47

Haemolytic disease of newborn Well developed in foetal cells at an early stage of foetal development Causes fatalities

Question 48

Kell specificities also cited in cases of patients with…

Answer 48

Both drug-induced and idiopathic AIHA Patients can transiently demonstrate weakening of the Kell system antigens and DAT may be only very weakly positive or negative. As the AIHA resolves to the levels of Kell system antigens return to normal

Question 49

Duffy (FY) Blood group system

Answer 49

- discovered in 1950 - named after a patient with haemophilia who had received multiple blood transfusions and was first known producer of anti-Fay - year later anti-Fyb was discovered in a woman who had several children -only FY3 appears clinically significant -erythrocytes and non-erythroid distribution (epithelial cells of kidney collecting ducts, lung tissue, purkinje cells of brain) - frequency varies in different populations

Question 50

Is Duffy present on lymphocytes, monocytes, granulocytes and platelets?

Answer 50

No

Question 51

Where are Duffy protein antigens , CD234, encoded for?

Answer 51

Chromosome 1

Question 52

More info on Duffy blood group system

Answer 52

5 antigens total, 2 major co-dominant alleles FYA and FyYB. Which result from a SNP

Question 53

Duffy glycoprotein

Answer 53

Receptor that binds cytokines during inflammation

Question 54

Duffy antigen receptor of chemokine

Answer 54

DARC Chemokine receptor on RBCs

Question 55

DARC

Answer 55

- receptor for 60% all inflammatory chemokine for both C-X-C and C-C classes - chemokine binding protein with no signalling function

Question 56

Function of DARC

Answer 56

Sink to bind excess chemokine prevents activation of neutrophils- benign ethnic neutropenia - reservoir for chemokine to maintain plasma chemokine concentration

Question 57

True FY(a-b-) phenotype

Answer 57

Have no obvious haematological or immunological abnormalities

Question 58

One mechanism for releasing chemokine from red cell surface

Answer 58

Clotting

Question 59

Fy(a-b-) phenotype and malaria

Answer 59

- Fy(a-b-) cells lack any Duffy glycoprotein expression on the RBC surface -Fy antigens are receptors for Plasmodium vivax merozoites (particularly associated with Fy6 expression) - Fy antigen serves as a receptor molecule for attachment of merozoites, absence of Fy antigens afffords selective advantage - Does not apply to other Plasmodium strains e.g., Plasmodium falciparum

Question 60

Duffy antibody characteristics

Answer 60

- Mainly IgG, as IgM is rare - stimulate by pregnancy/transfusion severity for both varies although usually mild HDFN - Anti-FYA 20x more common than anti-Fy in Caucasian populations -reactivity at 37 degrees, detected in AHG test -alloimmunisation to Duffy antigens not high indicating poor immunogenicity

Question 61

Duffy antibodies and HDN

Answer 61

Not a frequent cause, and where reported result in only mild cases requiring exchange transfusion

Question 62

Disease associations

Answer 62

- malaria - benign ethnic neutropenia -HIV disease progression - sickle cell disease- disease severity and organ damage -severity of immune reactions in autoimmune conditions - suppressive effect on angiogenesis and metastasis of cancer cells (interaction with CD82 which is a suppressor of metastasis)