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ABO BLOOD TYPE

INCOMPATIBILITY
Group IV- Sec B1
Members:
De Villa, John Vincent Paul
De Villa, Ma. Baby Jennica
Dela Chica, Julius
Dela Cruz, Juanito
Dela Cruz, Michael
Dela Cruz, Raymond Next
Dela Cruz, Crisida
OVERVIEW
I. Introduction
A. Definition of Terms
4. How do you make an Antigen?
B. The Discovery of ABO a. Precursor Substance
II. The Red Blood Cell b. Biochemical Structure of H Antigen
A. Definition c. Biochemical Structure of A Antigen
d. Biochemical Structure of B Antigen
B. Function
5. Composition of Antigen
C. Composition 6. Genetics in ABO
1. Major Integral Proteins
2. Peripheral Membrane Proteins IV. ABO Typing
III. Blood group Systems A. Blood typing
B. Blood Transfusion
A. Definition of terms
C. Transfusion Reactions
B. ABO blood group
C. Antigens V . Recap (by guide questions)
1. ABH Antigen
2. H Antigen
a. Bombay Group
3. ABO Substances
a. Glycosphingolipis
b. Glycoproteins
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DEFINITION OF TERMS
 Antigen: Any substance that when introduced in to, or present
in, the tissues or blood causes the formation of antibodies and
only reacts with its specific antibodies

 Antibody: A protein produced by certain cells of the body in the


presence of a specific antigen. The antibody combines with
that antigen to inhibit, neutralize or destroy it

 Agglutinogen: An antigen located on the surface plasma


membrane of RBC which determines the blood group of the
individual. Next
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DEFINITION OF TERMS
 Agglutinin: A specific antibody in blood plasma capable of
causing the clumping of RBC or bacteria or particles such as
viruses

 Agglutination: The clumping together of blood cells or


microorganisms, usually due to an antigen-antibody reaction

 Blood group: The type or specification of an individual’s bloo


according to the presence or absence of specific agglutinogens
on the red cells
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DEFINITION OF TERMS
 Blood transfusion: The introductioof blood from one person into
the circulation of another person

 Incompatibility: When the agglutinogens on the red cells in the


donor react with the agglutinins in the recipient’s blood.
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THE DISCOVERY OF ABO

Sturle and Von Descatello

AB

Karl Landsteiner
(1868-1943)
A, B, O
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THE RED BLOOD CELL


 Nonnucleated

 Biconcave in shape (This shape increases the surface-to-volume ratio


of the red blood cell, thus facilitating gas exchange. )

 Has simpler structure than most human cells, essentially


composed of a membrane surrounding a solution of
hemoglobin.

 No intracellular organelles, such as mitochondria, lysosomes,


or Golgi apparatus
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FUNCTIONS OF THE RED BLOOD CELL


 Delivers oxygen to the tissues

 Helps in the disposal of carbon dioxide and protons formed by


tissue metabolism.

 life span -120 days


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RBC COMPOSITION

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RBC COMPOSITION
Table 52–7. Summary of Biochemical Information About the Membrane of the Human
Red Blood Cell

•The membrane is a bilayer composed of about 50% lipid and 50% protein.
•The major lipid classes are phospholipids and cholesterol; the major phospholipids
are phosphatidylcholine (PC), phosphatidylethanolamine (PE), and
phosphatidylserine (PS) along with sphingomyelin (Sph).
•The choline-containing phospholipids, PC and Sph, predominate in the outer
leaflet and the amino-containing phospholipids (PE and PS) in the inner leaflet.
•Glycosphingolipids (GSLs) (neutral GSLs, gangliosides, and complex species,
including the ABO blood group substances) constitute about 5–10% of the total
lipid.

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RBC COMPOSITION

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RBC COMPOSITION
Table 52–7. Summary of Biochemical Information About the Membrane of the Human
Red Blood Cell (CONT)

•Analysis by SDS-PAGE shows that the membrane contains about 10 major


proteins and more than 100 minor species
•The major proteins (which include spectrin, ankyrin, the anion exchange protein,
actin, and band 4.1)
•Many of the proteins are glycoproteins (eg, the glycophorins) containing O- or N-
linked (or both) oligosaccharide chains located on the external surface of the
membrane.

Harper’s Illustrated Biochemistry, 28e

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PRINCIPAL PROTEINS OF THE RED CELL


MEMBRANE
Band Number1 Protein Integral (I) or Approximate
  Peripheral (P) Molecular Mass (kDa)
1 Spectrin (a ) P 240
2 Spectrin (B) P 220
2.1 Ankyrin P 210
2.2 Ankyrin P 195
2.3 Ankyrin P 175
2.6 Ankyrin P 145
3 Anion exchange protein I 100
4.1 Unnamed P 80
5 Actin P 43
6 Glyceraldehyde-3-phosphate P 35
dehydrogenase
7 Tropomyosin P 29
8 Unnamed P 23
Glycophorins A, B, and C I 31, 23, and 28
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THE MAJOR INTEGRAL PROTEINS OF THE


RBC
 Anion exchange protein (band 3)
 a transmembrane glycoprotein, with its carboxyl terminal end on the
external surface of the membrane and its amino terminal end on the
cytoplasmic surface.
 a multipass membrane protein, extending across the bilayer
approximately fourteen times
 exists as a dimer in the membrane, in which it forms a tunnel,
permitting the exchange of chloride for bicarbonate. Carbon dioxide,
formed in the tissues, enters the red cell as bicarbonate, which is
exchanged for chloride in the lungs, where carbon dioxide is exhaled.
 The amino terminal end binds many proteins, including hemoglobin,
proteins 4.1 and 4.2, ankyrin, and several glycolytic enzymes.
Purified band 3 has been added to lipid vesicles in vitro and has been Next

shown to perform its transport functions in this reconstituted system.


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 Glycophorins A, B, and C

 also transmembrane glycoproteins but of the single-pass  type,


extending across the membrane only once.
 A is the major glycophorin, is made up of 131 amino acids, and is
heavily glycosylated (about 60% of its mass).
 Its amino terminal end, which contains 16 oligosaccharide chains
(15 of which are O-glycans), extrudes out from the surface of the red
blood cell. Approximately 90% of the sialic acid of the red cell
membrane is located in this protein.
 The carboxyl terminal end extends into the cytosol and binds to
protein 4.1, which in turn binds to spectrin.
 Glycophorin A contains binding sites for influenza virus and for
Plasmodium falciparum, the cause of one form of malaria.
Intriguingly, the function of red blood cells of individuals who lack
glycophorin A does not appear to be affected.
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THE PERIPHERAL MEMBRANE PROTEINS


 Spectrin
 major protein of the cytoskeleton, composed of two polypeptides:
spectrin 1 ( chain) and spectrin 2 ( chain).
 These chains, measuring approximately 100 nm in length, are
aligned in an antiparallel manner and are loosely intertwined,
forming a dimer.
 Both chains are made up of segments of 106 amino acids that
appear to fold into triple-stranded -helical coils joined by nonhelical
segments.
 One dimer interacts with another, forming a head-to-head tetramer.
The overall shape confers flexibility on the protein and in turn on the
membrane of the red blood cell. At least four binding sites can be
defined in spectrin: (1) for self-association, (2) for ankyrin (bands Next

2.1, etc), (3) for actin (band 5), and (4) for protein 4.1.
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 Ankyrin

 pyramid-shaped protein that binds spectrin. In turn, ankyrin binds


tightly to band 3, securing attachment of spectrin to the membrane.
Ankyrin is sensitive to proteolysis, accounting for the appearance of
bands 2.2, 2.3, and 2.6, all of which are derived from band 2.1.

 Actin (band 5)

 exists in red blood cells as short, double-helical filaments of F-actin.


The tail end of spectrin dimers binds to actin. Actin also binds to
protein 4.1.

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 Protein 4.1,

a globular protein, binds tightly to the tail end of spectrin, near the
actin-binding site of the latter, and thus is part of a protein 4.1-
spectrinactin ternary complex. Protein 4.1 also binds to the integral
proteins, glycophorins A and C, thereby attaching the ternary
complex to the membrane. In addition, protein 4.1 may interact with
certain membrane phospholipids, thus connecting the lipid bilayer to
the cytoskeleton.

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Interaction of cystoskeletal proteins with each other and with certain integral proteins of the RBC.
DANG
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BLOOD GROUP SYSTEMS


 Discovered by Landsteiner
 30 human blood group systems have been recognized, the
best known of which are the ABO, Rh (Rhesus), and MN
systems.
 "blood group" applies to a defined system of red blood cell
antigens (blood group substances) controlled by a genetic
locus having a variable number of alleles (eg, A, B, and O in
the ABO system).
 "blood type" refers to the antigenic phenotype, usually
recognized by the use of appropriate antibodies.
DEFINITION OF TERMS Home

 Glucosyltransferase:
are enzyme that facilitate the transfer of carbohydrate molecules onto
carbohydrate precursor molecules.

 Immunodominant sugar:
is the sugar molecule that completes the antigenic determinant when
combined with the precursor substance.

 Amorph:
a mutant allele that has little or no effect on the expression
of a trait

 Allele:
any alternate form of a gene that can occupy a given chromosomal
location (Locus).
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ABO BLOOD GROUP SYSTEM


 Based on two agglutinogens referred to as A and B.
 Individuals whose erythrocytes develop only Antigen A are said
to have blood type A.
 Those whose erythrocytes develop only agglutinogen B are
said to have blood group B.
 Some individuals, who have erythrocytes which develop both
agglutinogen A and B, are said to have blood group AB.
 Those individuals who manufacture neither agglutinogen are
said to have blood group O.

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 The blood group agglutinins, a and b, are present in the


plasma of the individuals.
 Blood group A plasma contains agglutinin b.

 Blood group B plasma contains agglutinin a.

 Blood group AB contains neither of the agglutinin.

 Blood group O contains both agglutinin a and b.


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RED CELL ANTIGEN


Antigens are inherited

Real function unknown

Damn important during transfusion

Lots of antigens exist (grouped into systems)

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BLOOD TYPE (OR BLOOD GROUP) IS DETERMINED, IN PART,
BY THE ABO BLOOD GROUP ANTIGENS PRESENT ON RED
BLOOD CELLS
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ABH ANTIGEN
 The inheritance of ABO blood group demonstrates that
each individual inherits ABO gene from each parent and
these two genes will determine the antigen present on
RBC membrane.

 One position or locus on each chromosome 9 is


occupied by A, B, or O gene.

 A locus termed H and the final product of the genes at


that locus is H antigen. It is necessary for the expression
of normal ABO antigens.
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H ANTIGEN
 Basic structure molecule
 Required to produce either A and B antigens

 Detected using a specific antisera (lectin seed extract known


as Ulex europeaus)
 Each parent contributes one gene either, H or h. Giving
possible genetic combinations HH, Hh or hh.

H gene acts on a
Precursor
substance(PS)* *PS = oligosaccharide
by adding chain attached to
Fucose glycosphingo-lipid, Type
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2 chain (on RBC)
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H ANTIGEN
H h

H HH Hh

h Hh hh

 HH and Hh will produce the H antigen


 hh do not produce the H antigen and will have the
Bombay phenotype
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BOMBAY GROUP
 A very rare cases
 Red cells that are not agglutinated by Anti-A, Anti-B, or
Anti-AB
 Believed to be formed under the influence of suppressor
gene and are characterized by reactions resembling those
of O cells
 The plasma contains Anti-A and Anti-B, but the cells do
not react with Anti-H or with Anti-A or Anti-B
 Differentiation is based on the presence of Anti-H in the
plasma and a lack of H substance on the cells
 Normal group O blood do not possess Anti-H in the
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plasma, but do contain H substance on the cells


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BOMBAY GROUP

Cells Contain Serum Contains

Anti-A1
Bombay Group ----------------- Anti-B
Anti-H

Group O H Substance Anti-A1


Anti-B
ABO SUBSTANCES : Home

GLYCOSPHINGOLIPIDS &
GLYCOPROTEINS

 ABO substances 
 Are complex oligosaccharides present in most cells of the body and in certain
secretions
 On membranes of red blood cells, the oligosaccharides that determine the
specific natures of the ABO substances appear to be mostly present in
glycosphingolipids
 whereas in secretions the same oligosaccharides are present in glycoproteins.

Their presence in secretions is determined by a gene designated Se  (for


secretor ), which codes for a specific fucosyl (Fuc) transferase enzyme  that
adds fucose onto Type I chains primarily in secretory glands. Individuals of
SeSe or Sese genotypes secrete A or B antigens (or both), whereas individuals
of the sese genotype do not secrete A or B substances, but their red blood cells
can express the A and B antigens.
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HOW DO YOU MAKE AN ANTIGEN?


Start with a protein precursor

Add fucose to make H antigen

Add N-acetylgalactosamine to H Ag to make A Ag

Add galactose to H Ag to make B Ag


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Biochemical structure of
Precursor Substance
A, B and H antigens are built on
oligosaccharide chains of 4 types.
The most common forms are Type
1 and Type 2.

Type 1: Carbon one of Gal is


attached to the carbon three of
GlcNAc.

Type 2: Carbon one of Gal is


attached to the carbon four of
GlcNAc.
Biochemical structure of H antigen
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H gene acts on a
Precursor
substance(PS) by
adding L-fucosyl
Fucose transferase

Precursor Substance-
Oligosaccharide chain
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Biochemical structure of A antigen

N-acetyl-galactosamine
added to H substance GalNAc
transferase

H gene acts on a Precursor


substance(PS) by adding L-fucosyl
Fucose Precursor substance-
transferase
oligosaccharide chain
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Biochemical structure of B antigen

D-galactose added to H
D- galactosyl
substance
transferase

H gene acts on a Precursor


substance(PS) by adding L-fucosyl Precursor Substance
Fucose transferase -oligosaccharide chain

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 Blood Group O people have red blood cells rich in H


antigen. Why?
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Donor Nucleotides & Immundominant Sugars responsible for


H, A, and B Ags specificity
Antigen Immunodominant sugar Nucleotide Glcosyltransferase Gene

H L-fucose Guanosine
L- fucosyl transferase H
GDP-FUC

A N-acetyl-D- Uridine N acetylgalactosaminyl A


galactoseamine UDP- transferase
GALNAC

B D-galactose Uridine
D- galactosyl B
UDP-GAL transferase
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ABO Genetics
 Genes at three separate loci control the occurrence and location of A and B
antigens
1. Hh gene – H and h alleles (h is 1. Controls presence of H, A, and B
antigens on both RBCs and in
an a morph) Secretions

2. Se gene – Se and se alleles (se is 2. Controls presence of ABH


an amorph) antigen in the secretions

3. ABO genes– A, B and O alleles 3. Inherit 1 gene from each parent


that codes for an enzyme that
adds a sugar to the H antigen

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Blood
Genotype Antigens
type
AA
A A
AO
BB
B B
BO
AB A and B AB
OO None O
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BLOOD TYPING, TRANSFUSION,


REACTIONS
 Doc Jennyca De Villa
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ABO TYPING
2 Methods:
 Direct/Toward/Cell Grouping – Testing the patients red cell
using known antisera
Anti-A : Blue
Anti-B : Yellow

 Indirect/Reverse/Serum Group – Testing the patients using


known cells (To detect Antibodies)
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ABO SYSTEM IN BLOOD TRANSFUSION


Type A have anti-B antibodies in their plasma, thus agglutinate type B or type AB blood.
Type B have anti-A antibodies and will agglutinate type A or type AB blood
Type AB blood has neither anti-A nor anti-B antibodies (universal recipient)
Type O blood has neither A nor B substances (universal donor)

Explanation of these findings is related to the fact that the body does not usually produce
antibodies to its own constituents.

Thus, individuals of type A do not produce antibodies to their own blood group substance, A,
but do possess antibodies to the foreign blood group substance, B, possibly because similar
structures are present in microorganisms to which the body is exposed early in life.

Since individuals of type O have neither A nor B substances, they possess antibodies to
both these foreign substances.
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RED BLOOD CELL COMPATIBILITY TABLE


Recipient[1 Donor[1]
O− O+ A− A+ B− B+ AB− AB+
O−
O+
A−
A+
B−
B+
AB−
AB+

Table note
Assumes absence of atypical antibodies that would cause an incompatibility between
donor and recipient blood, as is usual for blood selected by cross matching.
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UNTOWARD EFFECTS OF BLOOD


TRANSFUSION
 Hemolytic Transfusion Reactions
 Anaphylaptic and Allergic Reactions

 Circulatory Overload

 Bacterial Reactions

 Miscellaneous Acute Problems

 Delayed Effects

 Transmission of Diseases

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HEMOLYTIC TRANSFUSION
REACTIONS
 The most dreaded transfusion reaction
 Results from acute hemolysis of donor’s red cells as they enter the
circulation of the recipient
 Caused by ABO incompatibilty which most frequently results from some
form of clerical error
 Signs and Symptoms:
 Fever
 Chills
 Flushing
 Nausea
 Burning at the intravenous (IV) line site
 Chest tightness
 Restlessness
 Apprehension
 Joint pain Next

 Back pain
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ANAPHYLACTIC AND ALLERGIC


REACTIONS
 Happens very rapidly as the transfusion begins
 Requires immediate intervention

 Cause by a rapid antibody reaction to a plasma protein


lacking the recipient
 Signs and Symptoms:
 Urticaria or Hives

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CIRCULATORY OVERLOAD
 Sudden increase in circulating blood volume are not well
tolerated by patients with:
 Cardiac / Pulmonary diseases
 Very anemic patients
 Infants

 Signs and Symptoms:


 Dyspnea
 Coughing
 Pulmonary Edema
 Cyanosis
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BACTERIAL REACTIONS
 When the donor’s blood is contaminated with large
numbers of living organisms
 Often caused by psychrophilic organisms

 Signs and Symptoms:


 Chills
 Headache
 Vomiting
 Muscle pains
 Diarrhea
 High Fever

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MISC ACUTE PROBLEMS


 Citrate Intoxication
 Hyperkalemia

 Hypothermia

 Pulmonary insfuciency due to debris in stored blood

 Air embolism

 Hemolysis due to overheated blood

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DELAYED EFFECTS
 Delayed hemolytic reactions
 5-7 Days
Reason: A previously immunized recipient may have little or no
circulating antibody at the time compatibility tests are
performed.

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TRANSMISSION OF DISEASES
(UNLUCKY ONES)
 Viral Hepatitis

 Cytomegalovirus Infection

 Syphilis

 Malaria

 AIDS
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GUIDE QUESTIONS
 What are the compositions of RBC?
 Discuss the Biochemical Basis of blood typing and blood type
determination.
 Explain the importance of the oligosaccharide sequence in the
RBC membrane in blood type determination.
 Explain the role of genetics in determining the blood type,
especially in the oligosaccharide content of membrane
lipoproteins.
 Discuss the biochemical basis of ABO incompatibility.