DIDACTICS Flashcards by Kyra Catedral

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Karl Landsteiner

He discovered the ABO blood group in____
He was also the first individual to perform for…

1901

forward and reverse typing.

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ABO BLOOD GROUP SYSTEM

ISBT number:_____
Chromosome____

001

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It is the only blood group system in which individuals have antibodies in their serum to antigens that are absent from their RBCs.
This occurs without any exposure to RBCs through transfusion or pregnancy.

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Are described as “____occurring” because they are produced without any exposure to antigens.

Predominantly______

Activate complement and react at______ temperature

It produces strong_______ reactions during ABO testing

naturally

IgM

room temperature or colder

direct agglutination

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It is initiated at birth ⟶ titers are generally too low for detection until the individual is_______ of age

Peaks: between_____ of age

Declines later in life

3-6 months

5-10 years

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INHERITANCE OF THE ABO BLOOD GROUP SYSTEM

It was first described by_____ in 1924.

It follows the simple Mendelian Genetics

Bernstein

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The sequence of DNA that is inherited from both of the parents.

It determines the phenotype.

It can be heterozygous or homozygous.

Genotyping

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________- inheritance of different alleles.
- for example: genotype AB ⟶ blood type AB (phenotype)

_________- inheritance or presence of two identical alleles
- for example:
genotype AA ⟶ blood type A (phenotype)
genotype OO ⟶ blood type O (phenotype)

Heterozygous

Homozygous

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Produced by the genotype
The antigen that was presented in the red cell.

Group _______are dominant gene.

Group____ are autosomal recessive gene. It is amorph, as no detectable antigen is response to the inheritance of this gene.

Phenotyping

A and B

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= Group A and B
= AA, BO, OO

Phenotype

Genotype

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Serologically, IT IS NOT POSSIBLE to determine the______ from phenotype of an A or B individual.

____ or ____are needed to perform to determine the exact genotype.

genotype

Family studies or Molecular assays

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The formation of ABH antigens results from the interactions of genes at three separate loci: (3) -

Take note: these genes do not code for the production of antigens but rather produce specific_____\ that add sugars to a basic precursor substance.

ABO, Hh, and Se

glycosyltransferases

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is the basic precursor material where A, B, and H antigens are formed to which sugars are attached in response to specific enzyme transferases elicited by an inherited gene.

_____- is the precursor structure on which A and B antigens are made.

Inheritance of H gene ⟶ formation H antigen

Paragloboside or Glycan

H antigen

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H and Se gene are found on chromosome

T1
T2

Linkage??

Se
H

B1-3
B1-4

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FORMATION OF H ANTIGENS

The H gene elicits the production of an enzyme called________ which transfers the sugar______ to an oligosaccharise chain on the terminal galactose of type 2 chains

Enzyme: a-2-L-fucosyltransferase Immunodominant sugar: L-fucose

HH or Hh genotype
hh genotype

a-2-L fucosyltransferase

L-fucose

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Most H to Least H

O > A2 > B > A2B > A1 > A1B

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The A gene (AA or AO) codes for the production of_____, which transfers an _____sugar to the H substance.

The A-specific immunodominant sugar is linked to a type____ precursor substance that now contains H substance through the action of the H gene.

a-3-N-acetylgalactosaminyltransferase

N-acetyl-D-galactosamine (GalNAc)

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FORMATION OF B ANTIGENS

Individuals who are blood group B inherit a B gene (BB or BO) that codes for the production of______, which attaches _____sugar to the H substance previously placed on the type 2 precursor substance through the action of the H gene.

α-3-D galactosyltransferase

D-galactose (Gal)

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ENZYMES

H
A
B

a-2-L-fucosyltransferase

a-3-N-acetylgalactosaminyltransferase

a-3-D-galactosyltransferase

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The A gene (AA or AO) codes for the production of_____, which transfers an _____sugar to the H substance.

The A-specific immunodominant sugar is linked to a type____ precursor substance that now contains H substance through the action of the H gene.

a-3-N-acetylgalactosaminyltransferase

N-acetyl-D-galactosamine (GalNAc)

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SUGARS

H
A
B

L-fucose

N-acetyl-D-galactosamine

D-galactose

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ABH antigens are integral parts of the
membranes of RBCs,
endothelial cells,
platelets,
lymphocytes, and
epithelial cells.

ABH-soluble antigens can also be found in all body secretions.

Their presence is dependent on the ABO genes inherited and on the inheritance of another set of genes called_______ that regulate their formation.

Sese (secretor genes)

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= people who inherit the sese genotype

Example: a group A individual who is a secretor (SeSe or Sese) will secrete_____ carrying A and H antigens.

Nonsecretors

glycoproteins

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FLUIDS IN WHICH A, B, AND H SUBSTANCES CAN BE DETECTED IN SECRETORS "DUBSTAMP"

Digestive juices Urine Bile Saliva Tears Amniotic fluid Milk Pathological fluids: Pleural, Peritoneal, Pericardial, Ovarian Cyst

EXCESSIVE ABH SUBSTANCES CAN BE OBSERVED IN "PIC"

• Pseudomucinous ovarian cyst • Intestinal Obstruction • Carcinoma of stomach and pancreas

ABH ANTIGENS ON RBCs RBC antigens can be (3) RBC antigens are synthesized only on type___ precursor chains. Type 2 chain refers to a ____linkage in which the number one carbon of the galactose is attached to the number four carbon of the N-acetylglucosamine sugar of the precursor substance. The enzyme produced by the H gene (0-2-1-fucosyltransferase) acts primarily on type 2 chains, which are prevalent on the RBC membrane.

glycolipids, glycoproteins, or glycosphingolipids. 2 beta 1→4

A, B, AND H SOLUBLE SUBSTANCES Secreted substances are_____. Secreted substances are primarily synthesized on type____ precursor chains. Type 1 chain refers to a ____linkage in which the number one carbon of the galactose is attached to the number three carbon of the N-acetylglucosamine sugar of the precursor substance. The enzyme produced by the Se gene (a-2-L-fucosyltransferase) preferentially acts on type 1 chains in secretory tissues.

glycoproteins 1 beta-1→3

represent phenotypes showing weaker variable serologic reactivity with the commonly used human polyclonal anti-A, anti-B, and anti-A,B reagents. Differ quantitatively on the amount that is express on the red cell membrane Differ qualitatively: linear or branched

ABO subgroups

: Amorphic; It does NOT code for any enzymes and is merely a representation of the absence of A and B genes/antigens : Higher concentrations of transterases than B gene. Has ___Ag sites on an A1 adult RBC. B gene: has_____ Ag sites A&B genes:_____ compete more efficiently for the H substance than the_____; A-600,000 sites B - 720,000 sites

O gene A gene = 810,000 to 1,170,000 B gene = 610,000 to 830,000 B enzyme/ A enzyme

- an individual inherits one ABO type B gene from each parent and that these two genes determine which ABO antigens are present on the RBC membrane (follows simple Mendelian genetics)

Codominance expression

Most common to least common blood types:

Type O > A > B > AB

- an individual inherits one ABO type B gene from each parent and that these two genes determine which ABO antigens are present on the RBC membrane (follows simple Mendelian genetics)

Codominance expression

O A B AB JANSKY (CZECH) MOSS (US)

1234 4231

ABO ANTIGENS - Form as early as the_____ day of fetal life, though RBCs of neonates carry only 25-50% of the number of antigenic sites found on adult RBCs - Full expression of antigens is found at____ of age and remains constant throughout life - The antigens can be found on RBCs, endothelial cells, platelets, lymphocytes, epithelial cells, and secretions (plasma soluble substances)

37th 2-4 years

- Individuals with the secretor gene (Sese or SeSe) aptly called ‘secretors’, comprise____% of the population - Those who do not have the gene (sese) are called “non-secretors” and comprise of the remaining___%

80 20

Determination of Secretor Status: o Specimen: o The principle of the test is that if ABH antigens are present in a soluble form in a fluid they will neutralize their corresponding antibodies and the antibodies will no longer be able to agglutinate red cells possessing the same antigens  If antigen is present = no agglutination  If antigen is absent = agglutination

Hemagglutination Inhibition saliva

H gene is found in___ of the population

> 99.99%

Forms of H antigens: : unbranched straight chains : complex branched chains

 H1 and H2  H3 and H4

Initiated in 1911 by______: discovered that the A phenotype has 2 subtypes (A 1 gene and A 2 gene) 1. Both A 1 and A 2 genes code for the same enzyme which transfers N-galactosamine sugar on either the branched (H3 /H4 ) or linear (H1 /H2 ) H antigens to become either A or A 1 antigens a. Transferase enzyme: b. ↑ enzymes = ↑ H antigens placed with N-acetylgalactosamine sugar to be converted to_____

von Dungern α-3-N-acetyl-D-galactosaminyltransferase A1 antigen

A1 React with A2 React with____ only Аз MF reaction with_____ Ax React with_____, No reaction with____

anti-A1 and anti A anti-A anti-A and anti-AB Anti-AB / anti-A

MF reaction with anti-A and anti-AB; but with only few agglutinates (<10% of cells) Weak/No reaction with anti-A and anti-AB No reaction with anti A and anti-AB No reaction with anti A and anti-AB Observed in siblings; A germline mutation of an A gene

Aend Am Ay & Ael Ay

is defined as small agglutinates within predominantly unagglutinated red cells

*Mixed field

is the method used to confirm the presence of Am, Ay, and Ael antigens

Adsorption and Elution of anti-A

______ Cells contain both “A1 ” antigens and “A” antigens = react with both anti-A 1 and anti-A antibodies Makes use of: ________antigens since A antigen is linear ________antigens since A 1 is branched

A 1 linear (H1 /H2 ) branched (H3 /H4 )

______Cells is thought to be simply “A” antigen with no “A1 ” antigen = react with anti-A antibodies only Only makes use of: ______antigens because it only bears the linear A antigen

A 2 linear H 1 and H 2

TWO WAYS TO DIFFERENTIATE A 1 and A 2 INDIVIDUALS

1. Adsorption (Use: SERUM of Type B individuals) 2. Use of Plant Lectin (Dolichos biflorus)

Adsorption (Use: SERUM of Type B individuals) Must agglutinate to say that the individual really is Type______(because A 1 antigen + anti-A 1 antibody from Type B serum = agglutination) If no agglutination = patient is Type____

A 1 A2

Use of Plant Lectin (Dolichos biflorus) Lectin are seed extracts that agglutinate human cells with some degree of specificity _____plant lectin has anti-A1 specificity similar to reaction with anti-A 1 antibody (agglutinates A 1 or A1 B only)

Dolichos biflorus

Characterized by: decreased number of A antigen sites per RBC varying degrees of agglutination by human AntiA,B increased variability in the detection of H antigen resulting in strong reactions against Anti-H presence/absence of Anti-A1 in the serum (will show weak agglutination with known A red cells in reverse grouping)

WEAK A SUBGROUPS

: highest number of antigens in the RBC : most common weak A subgroup identified with Anti-A,B (has the most antigens among the weak subgroup) : were postulated that they were due to a defective glycosyltransferase (only few H antigens are converted to A antigen

A1 A3 A3 , Ax , Am , Aend , Ay , A el

How to identify Weak A subgroups? Use______: strong agglutination indicates a lot of H antigens were unconverted Saliva studies suggests presence of H & A antigens Weak or no agglutination with Anti-A and Anti-A,B commercial reagents No agglutination with Anti-A1 Strong agglutination with Anti H

Anti-H lectin

MF reaction with anti-B and anti-AB Most frequent B subtype Weak reaction with anti-B and anti-AB No/Weak reaction with anti-B and anti-AB Converted to B if incubated with_____ No reaction with anti-B and anti-AB Extremely rare phenotype

Bз Bx Bm/ Uracil diphosphate Bel

: most common subgroup encountered in the lab : has the fewest antigens in the RBC has no reactions with anti-A,B (mistyped as O)

B3 B el B m and B el

is the method used to confirm the presence of B mand Bel

ADSORPTION and ELUTION of anti-B

Bombay Phenotype (On/Hnul/hh non-secretor) First reported by Dr. Y.M. Bhende in 1952 in Bombay (Mumbai), India Homozygous inheritance (hh genes) of the h gene results in the inability to form the H antigen and subsequently the A or B antigens. hh genotype

Bombay Antibodies present in the serum

Anti-A, Anti-B, Anti-AB, and Anti-H

can donate to any ABO blood group but can only be transfused with blood from another … - Phenotypes as blood group…

Bombay phenotype O

Very weak/absent H antigen on RBCs A or B antigens may be present in trace amounts (detected by adsorptionelution) Inherited via mutated/silenced FUT1 (H gene) Anti-H weaker than Bombay but may react at 37°C

Para-Bombay Phenotype

Universal RBC Donor: Universal Plasma Donor:

Type O Type AB

Universal RBC Recipient: Universal Plasma Recipient:

Type AB Type O

Most dangerous ABO transfusion:

Type A blood to Type O recipient

DIDACTICS Flashcards

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