BIOL 620 1st Edition Lecture 6 Outline of Current LectureImmunology: Secondary Structures of hemoglobin molecule:Current LectureAllotype: Variations outside the motifs gives allotype. Allotype with isotype has slight amino acid variation within alleles. Same isotype can have idiotype but not necessary.Same allotype does not mean the same idiotype.Domains: There are intra- chain disulphide bonds as well as inter- chain disulphide bonds with light chain and heavy chain.Sequence amino acids in each domain:CH 1 125 amino acids CH 2 375 nucleotides Due to repeated mutations in ancestral genome, there are 3 sequences coding for related proteins. There is immunoglobulin supergene family.Biological functions of domains: Variable Domain- binds to Ag.CH1- serves as a arm to extend Ag binding site.- also donates cysteine to form disulphide bridge between heavy and light chain.- Stabilizes Variable (light) and Variable (constant) interaction.- Adds to Ab diversity.Hinge region- gives flexibility to arms.- twists at hinge region.- Rich in proline and cysteine whereby proline gives turn in hexagon structure.Ig M and Ig E – has no hinge region.- CH 1 takes over this role to Ab arm flexibility.CH 2 Domain- Resolves Ab in water.- Since Aqueous form nedded for serum.- Globular protein dissolves well.- Long peptides have lesser dissolution.- CH 2 region has amino acids with carbohydrate (oligosaccharide) side chains which push CH 2 domains apart and enhance solubility.- Complement activation.CH 3 – enhances phagocytic binding.- active role in opsonization and enhanced binding for phagocytosis when Ab is attached to Ag.Isotypes: Features and Functions:Ig G – 4 different gamma chains in genome.- 4 different Ig G subtypes vary in hinge region and number of disulphide bonds.Ig G1, Ig G3, Ig G4 – can cross the placenta.Ig G3 and Ig G 1 – activate complements. Also, Ig G3 has the strongest complement activation.Ig G1 and Ig G3 bind to Fragment C receptors. The Fragment C receptors bind to Fragment C fragment of Ig G molecule.Ig M – found in the surface of resting mature B- lymphocytes as a membrane bound Molecule.- One particular cell has 1 idiotype and plasma cell pentamer has same idiotype.- Is pentameric and 900 K Da.- When first produced has low affinity but high avidity due to its pentameric property.Plasma cell- produces Ig G, Ig A, and Ig E which is identical idiotype to B- cell. Ag size – different valence are due to Ag size. Small Ag has 2 neighboring Ag Ab binding site closer than heavy and light cahin of the molecule. Large Ag creates steric hindrance formed closest to arm.Function comparison between Ig M and Ig G:Function Ig M Ig E1. Phagocytic binding + -2. Complement activation + + + +3. Crossing placenta + -4. Agglutination + + + +Human Blood Groups: Ag on the cell surface as a side chain is added by enzymes. Gene mutation in enzyme, change in substrate specificity, causes the formation of B Ag. In blood group O, mutation results in none of Ag added. Since this group has no evolutionary demand, human genome is converting to O. B Ag present in Group A even without the Ag exposure, as infants non Ab present but develops due to plant and bacteria exposure. If blood A and blood B react, they cause Ab-Ag response due to cross reactivity. In cats, first transfusion results in Ab formation, so next transfusion becomes fatal. Also, Ig M recognizes Ag and determines Blood group. Ig M does not cross