ABO and Rh ABO and Rh Blood group Blood group
systemssystems
History.• 1900 Austria Karl
Landsteiner• Cell and serum
reactions• groups A, B and O.• Antibody to lacking
antigen
cells
--++++6
--++++5
---++-4
--+--+3
--+--+2
---++-1
654321
seru
m
Landsteiner K. Über agglutinationserscheinungen normalen menschichen blutes. Wien Klin Wochenschr 1901; 14: 1132-1134.
• 1902 von Decastello and Stürli - AB
Antigens and antibodiesAntigens and antibodies
ABO phenotype
Antigens on RBCs
Antibody in serum
A A Anti-BB B Anti-A
AB AB NoneO none Anti-A,B
Antigens are terminal sugars on oligosaccharides attached to membrane glycolipid and glycoprotein
β-1,3
β-1,3
β-1,4
α-1,2
N-acetyl-D-galactosamine
Red Cell Surface
D-galactose
N-acetylglucosamine
L-fucose
α-1,3
A Antigen
AA gene produces an gene produces an enzyme which adds enzyme which adds the A specific sugar the A specific sugar NAcGalNAcGal
β-1,3
β-1,3
β-1,4
α-1,2
N-acetyl-D-galactosamine
Red Cell Surface
D-galactose
N-acetylglucosamine
L-fucose
α-1,3
B Antigen
BB gene produces an gene produces an enzyme which adds enzyme which adds the B specific sugar D-the B specific sugar D-GalGal
Genotypes and Genotypes and PhenotypesPhenotypes
AAA
AO
BBB
BO
AB AB
OO O
ABOABO genes on chromosome 7 genes on chromosome 7one gene from each parentone gene from each parentA and B co-dominant; O amorphicA and B co-dominant; O amorphic
A O
A
B O
B
A B
AB
A O B O O O
A B O
Phenotype
Genotype
Genotype
Phenotype
InheritanceInheritance..
Normal ABO Normal ABO GroupsGroups
Group Anti-A Anti-B A1 Red Cells
A2 Red Cells
B Red Cells
O Red Cells
A + - - - + -
B - + + + - -
O - - + + + -
AB + + - - - -
AntibodiesAntibodies• “Naturally occurring”• Predominantly complement binding
IgM.• Low levels of IgGCan cause:• Immediate and severe Haemolytic
Transfusion Reactions;• Mild to moderate Haemolytic Disease
of the Newborn
Transfusion practiceTransfusion practice
RecipientRecipient Donor product to be transfusedDonor product to be transfusedphenotypphenotyp
eeWhole bloodWhole blood RBCsRBCs PlasmaPlasma
AA AA A,OA,O A, ABA, ABBB BB B, OB, O B, ABB, AB
ABAB ABAB AB, A, B, OAB, A, B, O ABABOO OO OO O, A, B, ABO, A, B, AB
Identical ABO phenotype blood is best match Identical ABO phenotype blood is best match but where not available, use ABO-compatible but where not available, use ABO-compatible bloodbloodgroup O cells are group O cells are ““universal donorsuniversal donors””group AB - universal recipients group AB - universal recipients
Most DEATHS from blood transfusion caused by ABO incompatibility due to
avoidable clerical ERRORS!!!!
?Rh Bloodgroup ?Rh Bloodgroup systemsystem
• HISTORY• 1939 – Levine and Stetson • HDNB mother transfused with
and reacted to father’s blood• 1940 Landsteiner and Weiner• Immunised rabbits and guinea
pigs with Rhesus monkey cells
HistoryHistory1939 Levine and Stetson
Hydropicnewborn
Severely anaemic mother
Husband ABO compatible
Antibody in serum reacted with 85% of NY donors
Severe
HTR
HistoryHistory
Antibody reacted with 85% of NY donorsboth antibodies named anti-Rhesus in errorAntigen detected by anti-rhesus monkey later re-named LW!!
1940 Landsteiner and Weiner
Macaco rhesus macaca mulatta
RBCs
GeneticsGenetics• chromosome1chromosome1• 2 genes 2 genes RHDRHD and and RHCERHCE – codominant – codominant• protein antigens protein antigens • 4 alleles can occupy 4 alleles can occupy RHCERHCE locus locus• RHce, RHcE, RHCE, RHCeRHce, RHcE, RHCE, RHCe• Inheritance of Inheritance of RHDRHD = RhD positive = RhD positive• D –ve individuals inherit only D –ve individuals inherit only RHCERHCE• there is no “d” antigen
DCedce
DCce
DcEdce
DcEe
DCeDcE
DCe
Phenotype
Genotype
Genotype
Phenotype
DCedce dceDcE dcedce
DCcEe DcEe ce
R1R2 R1R1 R2r rr
R1rR2r
inheritanceinheritance.
The D Antigen.The D Antigen.
AntibodiesAntibodies• Predominantly IgG occasional IgM
anti-E• Delayed Haemolytic Transfusion
Reactions– Extravascular haemolysis
• Haemolytic Disease of the foetus and newborn
• Warm Auto immune Haemolytic anaemia
The plasma The plasma membranemembrane
Lipid molecules are amphipathicamphipathic.
have both polar (charged) and nonpolar (uncharged) parts
75% are phospholipids
Plasma MembranePlasma Membrane• fluid mosaic model describes
– “sea of lipids in which proteins float like icebergs”
– 50 % lipid & 50 % protein •held together by hydrogen bonds
– lipid is barrier to entry or exit of polar substances
– proteins -“gatekeepers” -- regulate traffic
• 50 lipid molecules for each protein molecule
The Lipid BilayerThe Lipid Bilayer• Basic framework of the plasma membrane• Lipid: phospholipids, cholesterol, glycolipids
Membrane Lipid BilayerMembrane Lipid Bilayer
• Phospholipids, cholesterol, glycolipids
Membrane FluidityMembrane Fluidity
• Membranes are fluid structures, most of the lipids and many of the proteins easily move in the bilayer.
• Membrane lipids and proteins are mobile in their own half of bilayer.
• Cholesterol serves to stabilize membrane and reduce fluidity.
Membrane ProteinsMembrane Proteins
Integral versus Peripheral Proteins
Integral ProteinsIntegral Proteins
• many are glycoproteins.• combined glycoproteins and
glycolipids form the glycocalyx– cell recognition– Adherence– protection from digestion by
enzymes in extracellular fluid.
Functions of Membrane Functions of Membrane Proteins Proteins
• Formation of ChannelFormation of Channel– passageway to allow specific
substance to pass through• Transporter ProteinsTransporter Proteins
– bind a specific substance, change their shape & move it across membrane
• Receptor ProteinsReceptor Proteins– cellular recognition site–bind to
substance• EnzymesEnzymes
Functions of Membrane Functions of Membrane ProteinsProteins
• Cell Identity Marker– allow cell to recognize
other similar cells
• Linker– anchor proteins in cell
membrane or to other cells
– allow cell movement– cell shape & structure
Functions of Membrane Functions of Membrane ProteinsProteins
ChimkupeteBlood
• Definition• Properties• Composition
– Plasma– Cells
• Circulation– arteries, veins
• Functions
Haemopoiesis - Stages, role of growth factors
Pluripotent stem cell
Lymphoid stem cell
Monoblast
Platelets
Eosinophil
Basophil Neutrophil Monocyte
B lymhocyte
T lymphocyte
Plasma cell Macrophage
Reticulocyte
Myeloid stem cell
CFU-GM
CFU-ECFU-Meg
Proerythroblast Megakaryoblast Eosinophilic & Basophilic myeloblast Myeloblast
megakaryocyte
Erythrocyte
T lymphoblast & B lymhoblast
•NumbersNumbers•Morpholog
y•Formation •Maturation•Functions
Blood cells
• Lymphocytes & monocytes
•Morphology•Maturation•Functions