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