Immunoglobulins

Immunoglobulins

1. 5 classes

   • Ig A
     • Secretory- dimeric
       • has SC that protects in harsh enviroment of secretions
     • 2 subclasses IgA1/A2
     • Serum-monomeric
   • Ig D
     • Very low serum concentrations
     • Found on lymphocyte surface
     • Function unclear
   • Ig G
     • Most abundant Ig in plasma
     • It has 4 subasses-IgG1/G2/G3/G4
     • Efficient at triggering complement and phagocytosis via Fc receptors
     • Only antibody to cross placenta to foetus
     • Predominant antibody in 2nd response
   • Ig M
     • Only in plasma and secretion too large to enter tissue
     • Pentamer, joined by J chains and disulphide bridges
     • Heavy chains has 5 domains
     • good at agglutinating particles e.g viruses, efficient at activating complement
     • Predominant antibody in 1st response
   • Ig E
     • Extra C domain
     • Associated with allergic response
     • Protects against parasites

2. Structure of antibody

   • • Light chains have 2 types- Lambda and kappa
       • Fold up into 2 domaians-VL and CL, each domain made of 2 Beta sheets linksed b y a disulphide bridge
     • Heavy chain determines the class of the antibody
       • Fold into 4(5) domains-VH, CH1,CH2,CH3 (CH4)
   • Fab- responsible for binding the antigen
   • Fc-reponsible for effector function (clearance mechanisms)

3. How are antigens recognised?

   • 3 hypervariable loobs (CDR) in each variable domain (VH & VL) form the antigen binding site
   • Antibody recognises structural epitopes on the antigen
   • Binds antigen with non- covalent interactions

4. Effect of Antibodies

   • Blocking of entry to pathogens
     • Antibody binds to virus preventing it binding with receptors so preventing fusion event
     • Antibodies against adhesion bind to bacterial and prevent colonization and therefore uptake
   • Neutralisation of toxins
     • IgG and IgA bind to solube toxin preventing them from binding to cellular receptors and poisoning the cell
   • Activation of classical complement pathway (IgM or Ig G) which leads to bacterial cell lysis
     • IgM binds to antigens on bacterial surface, adopt staple form. C1q complex binds to IgM and activates C1r which cleaves and activates serine protease
     • IgG bind to antigens on bacterial surface. C1q cmplx binds to at least 2 IgG molecules. This activates C1r which cleaves and activates serine protease
   • Bacterial opsonisation
     • 1) Bacterial is coated in complement and antibody
     • 2) When complement bind to receptor and the antibody binds to the Fc receptor on macrophage membrane the bacteria is phagocytosed
     • 3) Macrophage membrane fuse forming a phagosome
     • 4) Lysosomes fuse with hagosome and release enzymes that degrade the bacteria
   • Fc mediated clearance through cross-links
     • Aggregation of antibody on bacterial surface allows cross-llinking of Fc receptor and activation of macrohage, leading to phagocytosis and destruction