The Framework of Host Innate and Adaptive Immunological Pathways

Background: Host immune responses can be broadly divided into innate and adaptive immunity. Numerous adaptive immune responses have been identified, including TH1, TH2, TH3, TH9, TH17, and TH22 immunity. Within innate immunity, Vγ9-chain γδ T cells are among the most extensively studied immune-cell populations. Knowledge Gap: However, the precise functional classification of these innate and adaptive immunological pathways in responses to different types of pathogens remains incompletely understood. Purpose of the Review: This review proposes an integrated framework for the detailed functional classification of host innate and adaptive immunological pathways. Proposed Framework: Within innate immunity, γδ T cells can be categorized into several functional groups. The clonal anergy and tolerance pathway is associated with Vγ2-chain γδ T cells. The host innate immunological pathway against viruses is associated with Vγ8-chain γδ T cells, whereas the pathway against intracellular microorganisms is associated with Vγ9-chain γδ T cells. The pathway against extracellular microorganisms is associated with Vγ4-chain γδ T cells, the pathway against helminths with Vγ5-chain γδ T cells, and the pathway against insects with Vγ3-chain γδ T cells. Within adaptive immunity, five eradicable immune reactions and four tolerable immune reactions are described. Among the tolerable immune reactions, TH3 is associated with interleukin-35-producing CD4 T cells, whereas TH4 is associated with interleukin-32-producing CD4 T cells. Significance: A more precise functional classification of innate and adaptive immunological pathways may provide a useful conceptual basis for combating infections and hypersensitivity disorders.