Antibody molecules Flashcards
Linus Pauling
Model proposed that a pre-formed, undifferentiated “immunoprotein”. Single immunoprotein react to all antigens. WRONG
Sir Frank MacFarlane Burnet
- Clonal Selection Theory. Somatic mutation during embryonic life - random specific antibodies. eliminate self-reactive antibodies
Antigens
Any molecule or part of a molecule that is recognised by a variable antigen-receptor on an immunoglobulin
Paratope
antigen-binding region of the natibody
epitope
specific region of antigen that binds to immunoglobulin
Heavy chain
55kDa. gamma, mu, alpha, delta, epislon.
Light chain
22kDa. kappa or lambda.
IgG
gamma heavy chain. monomer. valency of 2. circulating - greatest conc found in circulation
IgM
mu heavy chain. circulating. pentamer (with J chain). first response. low affinity. valency of 10.
IgA
alpha heavy chain. mucosal membranes. monomer, dimer or trimer (J chain). secretory component.
IgE
allergic reactions. epsilon heavy chain. monomer.
IgD
delta heavy chain. monomer.
Porter and Edelman
- Porter used papain (protease) to show that immunoglobulin has 3 fractions. Fraction 1 and 2 bound antigens - Fab. Fraction 3 crystallised - Fc. Edelman used pepsin (protease) to show IgG consisted of 4 chains (2x heavy and 2x light).
Vh and Vl
hyper-variability within four conserved framework regions (FR1, FR2, FR3, FR4). form loops that combine toghether to form antigen binding surfaces. complementary determining regions (CDR1, CDR2, CDR3) are important for engineering antibodies.
Trans-epithelial transport of IgA
IgA dimer with J chain binds to the polymeric Ig receptor (pIgR) - transmembrane protein expressed at basal surface of epithelial cells of gut and airways. Binding of IgA induces transcytosis of pIgR. Complex delivered into the lumen.
IgA secretory component
protects against proteases within mucus and anchors IgA at the desired location
Opsinisation and Phagocytosis
opsonise with IgA, Fca/uR binds to IgA (or IgM) to mediate uptake by macrophage and DC. FcaRI mediates uptake by neutrophil.
ITAM
immunoreceptor tyrosin-based activation motif. Contains precisely spaced tyrosines. always have leucine or isoleucine in amino acid repeat. When phosphorylated, the tyrosine residues provide a binding site for intracellular tyrosine kinases (Syk in most immune cells or ZAP-70 in T cells). These have SH2domain –> singal transduction