Biochem ABO Incompatibility
Biochem ABO Incompatibility
Biochem ABO Incompatibility
Group 6 Reporters: ESTRADA, James Raphael ESTEBAN, Laurence ESPERANZA, Wynwright Members: ESPINOSA, Kesshia ESQUIDA, Patria ESTEBAN, Emel Rose ESTRELLA, Lee Anne
LEARNING OBJECTIVES:
To describe the composition of RBC membrane To explain the importance of the oligosaccharide sequence in the RBC membrane in blood type determination To determine the role of genetics in determining the blood type, especially in the oligosaccharide content of membrane lipoproteins To illustrate the biochemical basis of blood typing and blood determination To identify the biochemical basis of ABO incompatibility
Primary function
Functions
Maintains the characteristic shape of the red cell Acts as the interface between the cell and its environment via membrane surface receptors
Composition
Membrane Carbohydrates Occur only on the external surface of the red cell as: Glycoprotein Glycolipids Ex. ABO blood group (antigen)
Composition
Composition
MEMBRANE PHOSPHOLIPIDS Polar head group hydrophilic(water loving) Non-polar fatty acid tail (Hydrocarbon chains) hydrophobic (water fearing)
Phospholipids
Phosphatidyl choline
Sphingomyelin
Phosphatidyl ethanolamine
Phosphatidyl
serine
Phosphatidyl Ethanolamine
Phosphatidyl Serine
MEMBRANE CHOLESTEROL
Unesterified Lies between the 2 layers of the lipid bilayer
MEMBRANE CHOLESTEROL
MEMBRANE CHOLESTEROL
surface area
deformability
Membrane Proteins
Peripheral Integral Named according to their relative positions on SDSPAGE electrophoresis
Membrane Proteins
PERIPHERAL PROTEINS
Interact to form a cytoskeleton. acts as a tough supporting framework for the lipid bilayer.
FOUR peripheral proteins play a key role in the structure of the red cell cytoskeleton:
Spectrin Ankyrin Protein 4.1 Actin
peripheral proteins
Spectrin (Bands 1 and 2) Most abundant consists of : - chain - chain Responsible for the flexibility of the RBC membrane Ankyrin(Bands 2.1-2.3) This serves to anchor assembled spectrin molecules to the lipid bilayer.
peripheral protei ns
Actin(Band 5) Globular protein Composed of filaments The filaments bind weakly to the tail end of both and spectrins. Band 4.1 Globular protein Binds to spectrin close to the actin binding site thereby strengthening and stabilizing the cytoskeletal lattice. Also binds directly to Glycophorins A and C and Band3. Strengthens the links between the lipid bilayer and the protein cytoskeleton.
Integral Proteins
These penetrate the lipid bilayer and are firmly anchored within it. -Band 3 -Glycophorins A, B, and C. -Na+/K+ ATPase. -glucose transport protein. -surface receptors.
Glycophorins
3 members of the RBC glycophorin family: Glycophorins-A,B and C Sialoglycoproteins (combination of a sugar and protein) Act as :
transmembrane signal transducers receptor for the Plasmodium falciparum protein PfEBP 2(erythrocyte binding protein 2)
Na+/K+ATPase
Catalyses the hydrolysis of ATP to ADP Each ATP molecule hydrolysed: Ejection of 3 Na+ ions transport of 2 K+ ions into the cell
Surface receptors
Most important surface receptor is transferrin receptor. Highest concentration on RBC surface. The receptor domain is capable of binding two transferrin molecules. Receptor-transferrin complexes are internalised. Iron released from the transferrin
IMPORTANCE OF THE OLIGOSACCHARIDE SEQUENCE IN THE RBC MEMBRANE IN BLOOD TYPE DETERMINATION
OLIGOSACCHARIDE
3-12 monosaccharide Attach to the proteins and lipids on the surface of erythrocytes
H Substance
Derivative of Type 2 Precursor Chain Can be inherited from a parent having either an HH or Hh genotype Elicits the production of fucosyl transferase
50% HH
HH
Hh 50% Hh
25% HH 50% Hh
Hh
Hh
25% hh
Bombay Phenotype (rare case)
ABO Substances
1. A Substance AA or AO is responsible for the production of N-acetylgalactosaminyl transferase, which attaches GalNAc to the terminal galactose of the H Substance Immunodominant sugar: N-acetylgalactosamine
AA AA
100% AA
AA Ao
50% AA
50% Ao
ABO Substances
2. B Substance BB or BO is responsible for the production of Galactosyl transferase, which attaches Gal to the terminal galactose of the H Substance Immunodominant sugar: Galactose
BB BB
100% BB
BB Bo
50% BB
50% Bo
AA BB
100% AB
AB AB
ABO Substance
3. O Substance Homozygous genotype OO does not express any enzyme that would attach any additional sugar to the H Substance O Substance: No immunodominant sugar
oo
oo
100% oo
AA oo
100% Ao
AO oo
50% AO
50% OO
AB oo
50% AO
50% BO
4 4
ABO System
Definition of Terms
Agglutinin Specific antibody in blood plasma capable of causing the clumping of RBC or bacteria or particles such as viruses Antibody which aggregates a particulate antigen Agglutinogen Antigen located on the surface plasma membrane of RBC which determines the blood group of the individual Stimulates the production of agglutinin Agglutination The clumping together of blood cells or microorganisms, usually due to an antigen-antibody reaction
A B AB O
A B A&B Neither
Plasma
Plasma Plasma
Plasma
No Agglutination Reaction
Rh System Rh+ (+ D antigen) Dominant (DD) Heterozygous Rh (- D antigen) Homozygous recessive (dd)
(Dd)
Transfusion Reactions
ABO incompatibility is the most potent cause of immediate hemolytic reactions