chapter 4 Flashcards
what chromosome is the gene for ABO & the gene for Hh on
ABO is on chromosome 9
Hh is on chromosome 19
A, B & O alleles
ABO system has 3 possible alleles A, B & O
A& B are co dominant only differing by 7 nucleotides( 4 differing amino acids)
O is a recessive amorph - from a single nucleotide deletion resulting in a premature stop codon = non functional group
coding for A& B antigens
genes code only for proteins no carbohydrates
- A & B antigens are carbohydrates so the gene codes for an enzyme ( protein) that makes the antigen
whats another name for the H gene
FUT1 ( fucosyltransferase I)
the action of the enzyme produced
H is a carbohydrate too
The H antigen
a carbohydrate
an amorph
the building block for A & B antigens
only one H is needed to produce H antigen ; if a person is hh they will not produce the enzyme therefore no H will be made
Bombay & para- bombay
hh genotypes very rare ( <0.1% worldwide)
this type of person will only be compatible with other bombay blood groups bc they have no H ( required for antigens to form on ) they will have no antigens & therefore develop antibodies to all antigens
ex. A/A, h/h
will have anti -A , anti-B , anti-A,B , & anti-H
Immunodominant sugars
each A, B & H gene codes for an enzyme that adds an immunodominant sugar which characterizes the corresponding antigen
ANTIGEN; SUGAR ( ENZYME )
H ; L- fucose ( alpha-1,2-L-fucosyltransferase )
A; N-acetyl- D - galactosamine ( alpha-1,3-N-acetyl- galactosaminyltransferase )
B; D-galactose ( A-1,3-D-galactosyltransferase )
Type 1 & Type 2 ABH precursors
Type 1 makes up the majority of precursors found in the gut, plasma & secretions(saliva, urine, milk)
-have a ß1-3 linkage
Type 2 precursor substances are found mainly on the RBCs & & come in the saliva
- have a ß1-4 linkage
frequency of the 4 most dominant ABO phenotypes
O……………….46%
A………………..42%
B………………..9%
AB………………3%
A1 & A2 % & similarities
variations in the A gene lead to subgroups of A or AB people; 80% are A1 or A1B with most of the remaining 20% being A2 or A2B
They both have the same immunodominant sugar A1 is dominant, A2 is recessive
Qualitative & Quantitative differences in A1 & A2
A being more efficient at converting H to A means:
Quantitatively this leads to more A on A1 cells than A2
Qualitatively A1 have an additional epitope, therefore A2 can develop an anti- A ( no such thing as anti-A2)
~1-2% of A2 will develop an anti-A1
~20-25% of A2B2 will produce an anti-A1
Anti - A1 significance
Anti-A1 is a naturally occurring, IgM ( cold) class antibody that is usually clinically insignificant however in some cases it can show reactivity at 37 degrees, leading to a reduced lifespan of transfused A1 cells
note: anti-A1 can be found normally in O & B individuals
other subgroups of A
most to least A antigen expressed:
A1> A2> A3> Ax> Aend> Ael
A3 will show Mixed field with A/A & A/A,B
Ax will show a weak reaction with A/A & A Rxn with A/A,B
unexpected cold antibodies vs Anti-A1
reactions with A1 cells could be anti-A1 or an unexpected cold antibody
testing the plasma of a patient with a suspected anti-A1 against O cells as a negative control will help confirm or rule out Anti-A1 presence
if (+)= O person
if (-)= A2 person
Reagents of Anti-A1 & Anti-H made from
some reagents are made form lectins ( extracts from plant seeds)
Anti- A1 is from the seed of Dolichos biflorus
Anti-H is from the seed of Ulex europaeus
subgroups of B
extremely rare
sometimes patients/ donors with a very weak subgroup of B will produce a weak anti-B
landsteiner’s lsw
in the ABO blood group system, unlike other blood group systems, everyone develops antibodies to antigens that aren’t on their own RBCs, without exposure to foreign RBCs.
they may result from environmental exposures, therefore they are called naturally occurring antibodies
- babies aren’t born with ABO antibodies, they develop them overtime ( tend to develop after ~3 months)
- ** this id why we don’t do reverse ABO typing on newborns
- ABO antigens are sufficiently developed at birth to be reliably detectable
ABO antibodies class and thermal range
ABO antibodies are IgM ( react best at cold temps) , bind complement & are capable of intravascular hemolysis
ABO have a large thermal range & will also react at body temp.
ABO antibodies can also be IgG & IgA.
IgG antibodies are esspecually prevalent in group O people( in particular anti-A,B)
Secretors
A, B & H antigens can be found in plasma of individuals with respective antigen, those antigens will only be found in secretions ( urine, saliva, milk) of about 80% of these people( if they have the secretor gene)
ABH antigens in secretions are primarily glycoproteins ( except for in milk & urine they are oligosaccharides)
Secretors have at least one inherited Se gene. The Se gene codes for a fucosyltransferase enzyme; similar to H gene, except Se gene product preferentially acts on type 1 precursors while H gene acts on the 2.
Se gene makes fucosyltransferase which converts type 1 precursor to Se
Se gene ( FUT2) is on chromosome 19, near H gene
non secretors
the se gene is like the h gene; its an amorph
people who are se/se wont produce A, B or H in their secretions
~20% of populations are non secretors & don’t produce functional fucosyltransferase; the type 1 precursor substance secreted into their fluids is not converted to H substance & therefore cannot convert into A or B antigens, regardless of their ABO genotype
ABH antigens in secretions on RBCs & in plasma
ABH antigens in secretions are primarily glycoproteins ( except for in milk & urine they are oligosaccharides; sugars not attached to either proteins or lipids)
ABH antigens can adsorb onto platelets & lymphocytes
granulocytes & monocytes do not possess ABH antigens
secretor or non secretor you will have ABH antigens on RBCs
Lewis antigens
Lewis antigens are not intrinsic to RBC cell membrane but are adsorbed from plasma onto the RBC. This begins after birth, the full expression of lewis antigens isn’t reached until ~age 7
( Lewis antigens shouldn’t be phenotype on neonates or children)
Transfused cells acquire the lewis type of the recipient
during Pregnancy the production of lewis antigens can diminish, resulting in a transitory Le(a-b-) phenotype; lewis phenotyping shouldn’t be done on pregnant people
any antibodies produced during pregnancy to lewis will diminish after
Lewis gene
Lewis antigen results form the presences of the lewis gene (FUT3) with or without secretor gene. if Le gene is present, an L-fucosyltransferase enzyme acts on type 1 chains, rsultingin Le^a antigen. Le^a is then absorbed onto RBC cell membrane; phenotype Le(a+b-)
Secretor gene & Lewis gene
If the secretor gene is also present with the lewis gene, the secretor transferase enzyme adds fucose to type 1 chains & then the lewis transferase enzyme adds another fucose to this H type 1 chain, forming Le^b antigen
Le^b will be more abundant but with Le^a & Le^b will be present in body fluids. RBCs will preferentially absorb Le^b & the phenotype will be Le(a-b+)
RBC of people with no Le genes will type Le(a-b-)