Red Blood Cell (RBC) Membrane Structure &

Blood Group Antigen Location.

Red blood cells have a very specialized cell membrane that

plays a crucial role in things like oxygen transport, flexibility,
and interactions with the immune system (which is where
blood groups come in!).
□ 1. Structure of the RBC Membrane

The red blood cell membrane is a complex,

dynamic structure composed of:

🔹 A. Lipid Bilayer
 Phospholipids: Amphipathic molecules that form a
bilayer—hydrophilic heads face outward, hydrophobic
tails inward.
 Cholesterol: Interspersed in the bilayer; helps with
membrane fluidity and stability.

🔹 B. Integral and Peripheral Proteins

  Span the entire lipid bilayer.
 Examples: Band 3, glycophorin A.
 Functions:
o Transport (e.g., anion exchange via Band 3).

o Structural support.

o Act as scaffolds for blood group antigens.

🔸 Peripheral Membrane Proteins

 Attached to the inner surface of the
membrane (cytoplasmic side).
 Form a cytoskeletal network.
 Main components: Spectrin, ankyrin, actin, protein
4.1R.
 Function: maintain the biconcave shape, elasticity,
and
deformability of RBCs.

🔹 C. Glycocalyx (Outer Surface)

 Made up of glycolipids and glycoproteins with
carbohydrate chains projecting into the extracellular
space.
 This is where many blood group antigens are
located.
□ 2. Blood Group Antigens
Blood group antigens are found on the outer surface of the
RBC membrane, mostly as part of glycoproteins and
glycolipids.

□ Where Are the Blood Group Antigens?

 ABO antigens: These are carbohydrate structures
attached to glycolipids and glycoproteins.
o Example: The A and B antigens differ in

their terminal sugar on a base H antigen.

 Rh antigens: These are protein-based and
embedded
within the membrane, especially the RhD
protein.
🔍 3. Location and Nature of Major Blood Group
Antigens

Blood
Antigen Where It's Found Structure Detail
Group
Type
System
Based on terminal sugar
Glycoproteins & residues (A: N-
Glycolipids (outer acetylgalactosamine, B:
ABO Carbohydrate surface of
galactose, O: no terminal
membrane) sugar)
Rh Transmembrane RhD protein spans the
(especially Protein proteins (mainly membrane 12 times; acts
D) RhD protein) like a channel-like protein
These proteins carry M and N
MNS Protein Glycophorin A and
antigens as well as s and S
B
antigens
Kell, Kidd, Integral membrane Some function as transporters
Protein
Duffy proteins (e.g., Kidd = urea transporter)

💡 How They’re Anchored in the Membrane

 ABO antigens are attached to glycosphingolipids or
glycoproteins via enzymatic glycosylation in the Golgi
apparatus before the RBC matures.
 Rh antigens are part of the Rh complex—a set of
proteins that insert into the membrane and associate with
cytoskeletal elements for stability.
□ Genetic Basis
 The presence or absence of specific enzymes
(glycosyltransferases) determines the ABO type.
o Example: The A allele encodes an enzyme

that adds
N-acetylgalactosamine to the H antigen.
 RhD is encoded by the RHD gene. If it's deleted or
nonfunctional, the person is Rh-negative.

□ Key Points
 ABO antigens are sugars added by specific enzymes
to the RBC surface.
 Rh antigens are proteins integrated into the
membrane.
 These antigens are genetically inherited and important
for:
o Blood transfusion compatibility

o Pregnancy (Rh incompatibility)

o Immune reactions
 □ Rhesus (Rh) Blood Group System
The Rh system is the second most important blood group
system after ABO. It has over 50 antigens, but the five
main ones are:
D, C, c, E, and e
Among these, D is the most clinically significant:
 If you have the D antigen → you're Rh positive (Rh⁺)
 If you lack the D antigen → you're Rh negative (Rh⁻)

□ Genetics Behind Rh System (CDE Nomenclature)

The Rh antigens are encoded by two closely linked genes on

chromosome 1:

Gene Codes for Notes

RHD D antigen Presence or absence determines Rh⁺ or
Rh⁻

C, c, E, and e Different allele combinations give rise to

RHCE
antigens different antigen patterns
□Example Genotypes:
Genotype (Haplotype 1 + Haplotype 2) D Status Expressed Antigens
CDe / cDe Rh⁺ C, c, D, e
Rh⁺ c, D, e
cDe / cDe
Rh⁺ C, c, D, E
cDE / CDE
Rh⁻ c, e (no D)
cde / cde
Rh⁺ C, c, D, e
CDe / cde
Rh⁺ C, D, E
CDE / CDE

Wiener Nomenclature(Alternative system)

Fisher-Race Wiener
Cde R₁
cDe R₀
cDE R₂
cde r
Cde r′
cdE r″
Oher Blood group
 Lewis
The Lewis system focuses on a single locus with 2 antigens, Le a and
Le b.
These antigens do not form an integral part of the red cell
membrane, but are soluble antigens which may be present in body
fluids and secretions.
They are adsorbed on to the surface of red cells if they are present in
the plasma in sufficient amounts.
There are only three phenotypes: Le(a-b-); Le(a+b-); and Le(a-b+).
Lewis phenotypes may change during pregnancy. Examples of
Le(a+b+) are only transient (lasting for only a short time;
impermenant).
Lewis antibodies are only found in Le(a-b-) individuals, and are almost
entirely IgM. They are the only blood group antibodies which have
never been implicated in HDN (hemolytic disease of the newborn.)

Lewis Antigens:
• Soluble anti gens produced by ti ssues and fDLJnd in body fluids
(plasma)
• Adsorbed on the RBC

RBC becoming an aniipen

Le s;cues
 Kell
° The Kell Systems antigens are found in only small amounts on the red
cell carried on a single protein. The function of this protein is unknown.
• Simi/or to the Rh system
• 2 major antigens {over 20 exist)
• K (tell), <9% of population
• k (cellano), >90% of population
• There are also lip a and lip b
4 The ilp(o+) phenotype and the Kp(o-b-) phenotype ore both rare.
4 The ilp(a-b-) is associated with chronic granulomatus disease (SGD), an
inherited defect in the bacterial capacity of neutrophils.
• The K and k genes are codominant alleles on chromosome 7 that
coc/e
for the antigens.
• K has approximately 3500 sites and k has between 2000 - 5000.
° Well developed at birth.
• The K antigen is very immunogenic (2”d to the D antigen) in
stimn/ating
set antibody production.
Antibodies to tell system antigens are IgG and can be detected by
ihu globulin
 MN
• There are two loci: M/N and S
S/s.
• Chromosome 4 contains these linked genes.
• The antigens are M, N, S, and
s.
• M & N located on Glycophorin A
• S & s and U located on
Glycophorin B
6 Glycophorin is a protein that
carries many RBC antigens

• Anti-M and anti-N occur in

human serum as natural IgM
antibodies if
the respective Ag is absent on
red cells.
• They are IgM antibodies (rarely
IgG) and they are clinically
insignificant.
• Anti-S and anti-s commonly develop immune characteristics (IgG
class) as a result of pregnancy or transfusion.
• They are clinically significant and can cause RBC destruction and HDN.
• They can be detected by antihuman globulin serum
 Duff
•
y
• The Duffy system is also a single locus with two antigens, Fy° and Fy .
A pair of predominant gènes (co-dominant allèles
b

found on chromosome 1):

• Fy° and Fy^ code for antigens
• Well developed at birth
• Biochemically, the Duffy antigens are glycoproteins that has an
external loop. This external loop can be destroyed by enzymes such as
ficin, papain, and trypsin.
• Duffy antibodies are almost exclusively lgG.
• Anti- Fy^ and Fy^ present in serum invariably as result of immune response
• Anti-Fy° can cause HDN and Hemolytic Transfusion Reaction (delayed) and anti-
Fybis
milder and no HDN cases have been reported but could possibly be a cause.
• They can be detected by AHG serum (React best in Coombs after 37 C incubation)
• They are inactivated by proteolytic enzymes (Reactions destroyed by enZym0 Of the
red cells)

9
 Kid
• 2 antigens (co-dominant alleles):
• Jk and Jk^
a
d
• Are inherited on chromosome 18 where urea transport
mechanisms are located.
• Well developed at birth
• Enhanced by enzymes
• Not very accessible on the RBC membrane
• The Kidd antigens are thought to be grouped very close together in clusters
on the red cell membrane.
• Cells that are Jk(a-b-) are less likely to lyse in the presence of
high concentration of urea. These antigens are inherited
by the co- dominant alleles Jka and Jkb that are high
frequency antigens.
 Lutheran
Lutheran Blood Group System has 2 co-dominant
alleles:
• Lu° and Lux
• Weakly expressed on cord Blood cells
• Most individuals (92%) have the Lux antigen, Lu(a-b+)
• The Lu(a-b-J phenotype is RARE

Anti-Lu°
• /gM and/gG
• Not clinically signi/icont
• Reacts at room temperature
• Mild HDN
• Naturally occurring or immune stimulated

Anti-Lub
• Rare because Lux is high incidence antigen
 Thank
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