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Fig. 1 | Theoretical Biology and Medical Modelling

Fig. 1

From: MiStImm: an agent-based simulation tool to study the self-nonself discrimination of the adaptive immune response

Fig. 1

Humoral adaptive immune response by the ERS and CRS model. The ERS model is described by (a), (b) and (c), while CRS models are described by (c) alone. a In the ERS model, a hypothesized weak affinity interaction begins in intrauterine life and keeps the immune image of self during the whole life. It is sufficient for homeostasis; low affinity BCR binds self-antigens and presents self-peptides in their MHCII to regulatory T helper (Threg) cells; this ensures B and Threg cell survival. b In the ERS model another hypothesized interaction, intermediate affinity interaction initiate the first line of defense against an infection; some B cells that have higher BCR affinity for the antigens of the pathogen capture pathogens with intermediate affinity and present foreign peptides in their MHCII. The foreign peptides indirectly inhibit binding of Threg cells to these B cells for a critical time period, then the B cells will secrete hypothesized danger signals. Danger signals activate local Th cells, which in turn, release interleukins that fuel local T cell activation. This way a non-specific, local polyclonal B and T cell activation is induced, which is the primary defense mechanism against infections in the ERS model. Clonal expansion requires affinity maturation, which results in a several magnitude increase of BCR affinity, typically over a time of one week. Random mutations cause the production of B cells with a broad range of affinities for their presented foreign antigen. B cells with unfavorable mutations will not get sufficiently activated by the foreign antigen and will die, while those with improved affinity will be stimulated to clone themselves. c Specific immune reaction, here called as strong affinity interaction, appears in both the ERS and CRS models and is supervised and supported by pathogen peptide-specific Th cells, which require direct contact via TCR to the MHCII of the expanding B cell clone. Such higher affinity interactions would then drive clonal T cell proliferation, activation, lysis of infected cells. Having cleared the infection, specific T cells could eventually become an expanded memory type T cell clone, while B cells could differentiate into infection specific antibody-producing plasma cells or memory B cells. This interaction usually needs several days to efficiently start

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