A model of neutralization of Chlamydia trachomatis based on antibody and host cell aggregation on the elementary body...

Humoral immunity is that aspect of specific immunity that is mediated by B lymphocytes and involves the neutralizing of pathogens by means of antibodies attaching to the pathogen's binding sites. Antibodies bind to and block ligand sites on the pathogen which prevents these sites from attaching to target cell receptors and so cell entry is inhibited. Many studies investigate the role of humoral immunity for protection against chlamydial challenge and they have shown that neutralization of the chlamydial body requires a large number of attached antibodies. Steric hindrance greatly influences the number of available sites that may be bound, reducing relative occupancy well below 100%. We model steric effects of antibody Fab fragment attachment indicating that they must be taken into consideration to accurately model valency, the number of available binding sites. We derive a partial differential equation for the number of antibody Fabs and host cell receptors that are aggregated to extracellular chlamydial elementary bodies. We consider steric effects in describing the size distribution of aggregates. Our theory is in good agreement with Monte Carlo simulations of binding. We use our theoretical prediction for the valency in a model for the in-host population dynamics of a chlamydial infection and we fit our model to experimental data.