The 3 major types of innate and adaptive cell-mediated effector immunity

J Allergy Clin Immunol. 2015 Mar;135(3):626-35. doi: 10.1016/j.jaci.2014.11.001. Epub 2014 Dec 18.


The immune system has tailored its effector functions to optimally respond to distinct species of microbes. Based on emerging knowledge on the different effector T-cell and innate lymphoid cell (ILC) lineages, it is clear that the innate and adaptive immune systems converge into 3 major kinds of cell-mediated effector immunity, which we propose to categorize as type 1, type 2, and type 3. Type 1 immunity consists of T-bet(+) IFN-γ-producing group 1 ILCs (ILC1 and natural killer cells), CD8(+) cytotoxic T cells (TC1), and CD4(+) TH1 cells, which protect against intracellular microbes through activation of mononuclear phagocytes. Type 2 immunity consists of GATA-3(+) ILC2s, TC2 cells, and TH2 cells producing IL-4, IL-5, and IL-13, which induce mast cell, basophil, and eosinophil activation, as well as IgE antibody production, thus protecting against helminthes and venoms. Type 3 immunity is mediated by retinoic acid-related orphan receptor γt(+) ILC3s, TC17 cells, and TH17 cells producing IL-17, IL-22, or both, which activate mononuclear phagocytes but also recruit neutrophils and induce epithelial antimicrobial responses, thus protecting against extracellular bacteria and fungi. On the other hand, type 1 and 3 immunity mediate autoimmune diseases, whereas type 2 responses can cause allergic diseases.

Keywords: T(C)1; T(C)17/T(C)22; T(C)2; T(H)1; T(H)17/T(H)22; T(H)2; Type 1 immunity; innate lymphoid cells; type 2 immunity; type 3 immunity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptive Immunity*
  • Autoimmunity / genetics
  • Basophils / immunology
  • Basophils / pathology
  • Biomarkers / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • Communicable Diseases / genetics
  • Communicable Diseases / immunology*
  • Communicable Diseases / microbiology
  • Communicable Diseases / pathology
  • Cytokines / immunology
  • Eosinophils / immunology
  • Eosinophils / pathology
  • Gene Expression
  • Humans
  • Hypersensitivity / genetics
  • Hypersensitivity / immunology*
  • Hypersensitivity / pathology
  • Immunity, Cellular*
  • Immunity, Innate*
  • Mast Cells / immunology
  • Mast Cells / pathology
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / pathology
  • Th17 Cells / immunology
  • Th17 Cells / pathology
  • Th2 Cells / immunology
  • Th2 Cells / pathology


  • Biomarkers
  • Cytokines