title: Replication slippage and the dynamics of the immune response in malaria: a formal model for immunity.
abstract: A simple mathematical model of the dynamics of malaria invasion is proposed. The model is based on the hypothesis that replication slippage (slipped strand mispairing occurring in replicating DNAs), likely to take place within regular, low-complexity, regions of the plasmodium genome, is a significant mechanism of the ability for the parasite to escape the host immune defence. The model reconciles the conclusions of other formal approaches like periodic bursts of parasitaemia and, in particular, it predicts that antibody cross-reactivity affects the level and the time profile of malaria recrudescence. It also suggests that an efficient strategy for the parasite to escape host humoral immune defences is to express a single antigen. Linking local complexity to antigenic variability tentatively allows prediction of new potentially immunogenic sequences in the plasmodium genome.
authors.affiliation: Université Denis Diderot, ITODYS, 1 Rue Guy de la Brosse, 75005 Paris, France. dodin@paris7.jussieu.fr
authors.forename: G
authors.initials: G
authors.lastname: Dodin
authors.forename: P
authors.initials: P
authors.lastname: Levoir
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D000940:Antigenic Variation / Q000235:genetics; D000953:Antigens, Protozoan / Q000276:immunology; D020137:Base Pair Mismatch / Q000235:genetics; D003198:Computer Simulation; D004261:DNA Replication / Q000235:genetics*; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology*; D006790:Host-Parasite Interactions / Q000276:immunology*; D006801:Humans; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D008954:Models, Biological; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D013997:Time Factors
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan