Lecture 14Antibody-Antigen Reactions无法晶示俊图片
Lecture 14 Antibody-Antigen Reactions
Binding of the epitope in theantigen binding siteGOOD FITPOOR FITantibody combiningsiteantigendeterminanthigh repulsionhighattractionlowattractionlowrepulsion
Binding of the epitope in the antigen binding site GOOD FIT POOR FIT antibody combining site antigen determinant high attraction low repulsion high repulsion low attraction
AntibodyAvidityMultiple interactions between antigen binding sites andepitopesGreater than additiveSimilartoVelcro More relevant to biologic systems than affinity
Antibody Avidity ◼ Multiple interactions between antigen binding sites and epitopes ◼ Greater than additive ◼ Similar to Velcro ◼ More relevant to biologic systems than affinity
Effect of multivalentinteractionsIgGIgMFabIgGantibody2upto10effective antibody valence1nnantigen valence1011107104104equilibrium constant(L/M)103-fold107-foldadvantage of multi-valenceaffinityaffinityavidityaviditydefinition of bindngintrinsic affinityfunctional affinity
Effect of multivalent interactions antibody Fab IgG IgG IgM effective antibody valence 1 1 2 up to 10 antigen valence 1 1 n n equilibrium constant (L/M) 104 104 107 1011 advantage of multi-valence - - 103-fold 107-fold definition of bindng affinity affinity avidity avidity intrinsic affinity functional affinity
Biological Consequences of AntibodyAffinity/AvidityNeutralization of toxinsComplementactivationImmune elimination of antigenVirus neutralizationMoreintense immunecomplex disease inanimalshigher levels of circulating antigen-antibodycomplexesmore intenselocalization of immunecomplexesonbasementmembranes.more severe impairmentof organfunction
Biological Consequences of Antibody Affinity/Avidity ◼ Neutralization of toxins ◼ Complement activation ◼ Immune elimination of antigen ◼ Virus neutralization ◼ More intense immune complex disease in animals ◼ higher levels of circulating antigen-antibody complexes ◼ more intense localization of immune complexes on basement membranes. ◼ more severe impairment of organ function