Access-Fate-Amplification (AFA): A Compartmental Decision Grammar for Allergic Disease

Abstract

Central thesis Antigen identity and clinical phenotype do not reconstruct causal architecture. AFA asks which causal object reached which compartment, how genuine non-self was antigen-specifically engaged, which qualitative programme Fate allocated, what state persisted, what executed the acute phenotype, and whether any true feedback return relation amplified it. Abstract Access–Fate–Amplification (AFA) is the genuine-non-self branch of Compartmental Decision Pathology (CDP). It applies when antigen-specific receptor engagement is followed by a physiological Fate operation that integrates contextual, tissue-derived and prior-state information to allocate qualitatively distinct immune programmes. The causal grammar is Perturbation → [Access when required] → Fate → Functional configuration → Amplification → Phenotype, with modes of interference acting orthogonally. Access is optional and relational; receptor binding, scalar activation, effector execution and the resulting immune state are not Fate. AFA v1.0 retains strong operation-level support from controlled OVA/TCR-transgenic systems in which fixed antigen specificity is redirected between regulatory and effector programmes. Hardy et al. provide a qualified four-test state anchor for a peanut-specific recall-memory disposition, while independently isolated Fate provenance remains open; Chapman and Bruton provide complementary history-content and persistent-reset evidence, leaving recurrent Fate a strong candidate rather than a closed anchor. IgE/FcεRI effector causality is strong, but generic feedback Amplification remains unclosed. The public v1.0 baseline synchronizes AFA with CDP v1.0 and strengthens causal-object, Access and boundary discipline. Atopic dermatitis separates barrier predisposition from Fate; thunderstorm asthma and local allergic rhinitis sharpen route and compartment; drug and excipient hypersensitivity show that the named product need not be the causal antigenic object; and Hymenoptera venom immunotherapy provides a human reconfiguration stress-test in which challenge outcome can change despite persistent sensitization markers. Similar clinical phenotypes can arise through non-AFA mechanisms, and a single disease may contain nested branch-specific episodes. No single AFA model currently closes Fate, an operation-derived Functional configuration, feedback Amplification and Access where required.