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Introduction. More than 250 unique RBC antigens have been Documented to date Around 30 Blood group antigens assigned Most discovered in the course of blood transfusion. Biological Functions of Blood group Systems. Blood group Ag: On cell surface of Molecules with Wide Structural Diversity

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introduction
Introduction
  • More than 250 unique RBC antigens have been Documented to date
  • Around 30 Blood group antigens assigned
  • Most discovered in the course of blood transfusion
biological functions of blood group systems
Biological Functions of Blood group Systems
  • Blood group Ag:
    • On cell surface of Molecules with Wide Structural Diversity
      • Carbohydrate epitopes on glycoprotein/glycolipid
      • Peptide Ag on Membrane Proteins
      • GPI-Linked
      • Carried by Complexes
      • Expressed on Non-Erythroid tissue
        • Transfusion
        • Organ Transplantation
        • Development
slide3

Biological Functions of Blood group Systems

  • Functional Diversity
    • Transporters/Channels
      • Transporting Water-Soluble molecules/compounds
      • Rh, Colton, Diago, Kx, Kidd
    • Receptors
      • Biological
        • Duffy, Knops, Indian
      • Microbial
        • MNS, P, Lewis, Duffy, Cromer
    • Adhesion Molecules
      • Leuthran, Xg, L-W, Indian
    • Role in Complement Pathway
      • Chido/Rodgers, Cromer, Knops
    • Enzymes
      • ABO, P, Lewis, H
    • Structural Proteins
      • Maintain Shape
      • MNS, Diago, Gerbich
receptor function of blood antigens
Receptor Function of Blood Antigens
  • Many Microorganisms Recognize CHO on Glycoprotein or Glycolipid
    • Galα1-4Gal motif on P, P1, Pk Blood Group  Upper Urinary Tract Infect
    • Globoside with P  B19 Parvovirus Infects RBC Progenitor; Start Anemia
    • Leb  H.Pyroli causitive Agent of Causitive Gastritis, Peptic Ulcers, Gastric Carcinoma
    • LPS Express phase varying Lewis Ag (Lex/Ley/Lea/Leb)
      • P.Falciparum Invasion & Sequestration
      • Sequestration  Resette* Formation or Cytoadhesion** of infected RBC
    • DAF(CD55) (Carrier of Cromer)  in P.Vivax; Receptor for Chemokine
    • CD77(Carrier of Pk)  Transduce Signal for certain B cell Apoptosis

*Mediated by CD35(CR1)[Carrier of Knops]; so Helgenson Phenotype (CR1-) unable to form Rosette

** Protective Endothelial Receptors and Cryptic RBC Antigens like on Attached Band3

adhesion molecules of blood groups
Adhesion Molecules of Blood Groups
  • Mediate Intracellular Adhesion mechanisms & Interactions with Proteins of the Extracellular Matrix
  • Example:
    • Sialyl-Lex(Lea)
      • Involved in Rolling of Leukocyte Emigration from Blood Stream
        • Leukocyte Defeciency Syndrome II
          • Mental & Psychomotor Development Anomoly
  • Presence Varies Greatly During Endothelial Differentiation  Different Functions
slide10

Adhesion molecules with or associated with blood groups. Schematic representation of red cell membrane adhesion proteins with blood group specificity. The region (light grey) above the phospholipid bilayer (4-5 nm) represents the “glycocalix” (about 12 nm). The Ig-like domains of IgSF protein members are indicated as well as the ligand(s) when known.

blood group abo
Blood Group: ABO
  • Chromosomal Location: 9q34.1-q34.2
  • Gene Product: α3-N-acetyl-D-galactosaminyl transferase, α3-3-D-galactosyltransferase
  • Biological Function: Enzyme
  • Antigen No.:5
  • Size: 40-42 Kdal
blood group mns
Blood Group: MNS
  • Chromosomal Location: 4q28-q31
  • Gene Product: Glycophorin A, Glycophorin B, Glycophorin E
  • Biological Function: P. falciparum receptor
  • Antigen No.: 43
  • Size: 36.20 Kdal
blood group p
Blood Group: P
  • Chromosomal Location:22q11.2-qter
  • Gene Product: Galactosyltransferase
  • Biological Function: Parvovirus B19 Receptor
  • Antigen No.: 1
blood group rh
Blood Group: Rh
  • Chromosomal Location: 1p36.2-p34
  • Gene Product: RHE, RHC, RHD (CD240)
  • Biological Function: CD241* Amonium transporter
  • Antigen No.: 55
  • Size: 30-32 Kdal
blood group lutheran
Blood Group: Lutheran
  • Traditional Name: Lu
  • Chromosomal Location: 19q12-q13
  • Gene Product: Lutheran Glycoprotein/ B-CAM (CD239)
  • Biological Function: Ligand = Laminin (chain α5)
  • Antigen No.: 21
  • Size: 78-85 Kdal
blood group kell
Blood Group: Kell
  • Traditional Name: K
  • Chromosomal Location: 7q33
  • Gene Product: Kell Glycoprotein(CD238)
  • Biological Function: Zn-Metalloproteinase Enzyme
  • Antigen No.: 27
  • Size: 93 Kdal
blood group lewis
Blood Group: Lewis
  • ISBN Name: LE
  • Chromosomal Location: 19q13.3
  • Gene Product: α-3/4 fucosyltransferase
  • Biological Function: Enzyme
  • Antigen No.: 6
  • Size:
blood group duffy
Blood Group: Duffy
  • Traditional Name: Fy
  • ISBN Name: FY
  • Chromosomal Location: 1q22-q23
  • Gene Product: Fy glycoprotein(CD234)
  • Biological Function: P.vivax receptor / chemokine
  • Antigen No.: 6
  • Size: 3-45 Kdal

DARC = Duffy Antigen / Receptor for Chemokine

introduction20
Introduction
  • Found 1950
    • Only on RBC
    • Well developed at birth
    • Uncommon cause of HDN
    • Significantly different in populations
    • in Blacks (fy a-/b-) in White (fy a+/b+) (fy a-/b+) (fy a+/b-)
    • IgG
    • Indirect Anti-globulin test
    • Ab stimulation upon transfusion/pregnancy/exposure
    • Ab does not bind Complement
    • DARC action is Calcium Independent Unlike other Chemokine Receptors
slide21
Pathologically  in Renal Tissue of

Children with Nephropathy

Hemolytic Uremic Syndrome

Endothelial cells at Inflammatory sites in acute Renal Transplant Rejection

7-TM Glycoprotein/G-Protein Coupled

Receptor for ProinflammatoryChemokines (Homology with IL-8 receptor) WBC Activation

Receptor for P. vivax and HIV-1

Tissue Disribution:

RBC

Endothelial cells

Post-Capillary Venule

DARC Binds CC & CXC