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INTRODUCTION

SUMMARY

Innate lymphoid cells (ILCs) are a distinct lineage of lymphocytes that differ from immune lymphoid cells by not expressing somatically rearranged genes encoding antigen specific receptors. They are important in maintaining the homeostasis of different tissues and they have been classified into group 1, 2, and 3 based on their homology in functions and cytokine production with the T-helper subsets Th1, Th2, and Th22/17, respectively. Natural killer (NK) cells are now considered to belong to group 1 ILCS. NK cells have a constitutive ability to mediate cytotoxicity of pathologic target cells and to secrete cytokines, participate in the innate resistance to intracellular pathogens and malignancies, and have a modulatory effect on adaptive immunity and hematopoiesis. NK cell activity is regulated by the opposite effects of activating and inhibitory receptors.

Acronyms and Abbreviations

ADCC, antibody- dependent cell-mediated cytotoxicity; CAR, chimeric antigen receptor; CHILP, common helper ILC progenitor; CKR, chemokine receptor; CLP, common lymphoid precursor, CTL, cytotoxic T lymphocytes; CTLA4,ccytotoxic T –lymphocyteantigen 4; EILP, early ILC precursor; GM-CSF, granulocyte-macrophage colony stimulating factor; HLA, human leukocyte antigen; IFN, interferon; Ig, immunoglobulin; IL, interleukin; ILC, innate lymphoid cells; iNK-Tcell, invariant NK-T cell; ITAM, immunoreceptor tyrosine-based activating motif; ITIM, immunoreceptor tyrosine-based inhibitory motif; KIR, killer cell Ig-like receptors; LCMV, lymphocytic choriomeningitis virus; LGL, large granular lymphocytes; LILR, leukocyte Ig-like receptor; LIT, lymphoid tissue inducer cell; MAIT, mucosal associated invariant T cells; M-CSF, macrophage colony stimulating factor; MHC, major histocompatibility complex; MR1, MHC Class I-like protein; NCR, natural cytotoxicity recptor; NFIL3, nuclear factor interleukin 3 regulated; NK, natural killer; PD1 programmed cell death protein 1; PDL1 ligand for programmed cell death protein 1; Rag, recombination-activating genes; STAT, signal transducer and activator of transcription; TCF1, T cell-factor 1; TCR, T cell antigen receptor; T. gonadii, toxoplasma gonadii; Th, T helper; TNF, tumor necrosis factor; Id2, transcriptional regulator inhibitor of DNA binding 2; WT1, Wilm’s tumour 1protein,

INNATE LYMPHOID CELLS

DEFINITION

Natural killer (NK) cells have been known for several decades as a subset of innate immune lymphocytes with cytotoxic activity and cytokine production similar to those of CD8+ cytotoxic T cells but not expressing the clonally distributed antigen-specific T-cell receptors (TCRs).1,2 Another innate lymphoid cell (ILC), the lymphoid tissue inducer (LTI) cell, was described in the 1990s in lymphoid tissues of neonatal mice.3 Immune T-helper cells during immune responses polarize into different subsets, namely, T-helper 1 (Th1), Th2, Th22/17, and T-regulatory cells (Tregs), that produce different arrays of cytokines and contribute different functions in the immunity to infections, antitumor response, tissue repair and inflammation.4–6 Similarly, new ILC populations have been identified that parallel the cytokine production ability of Th subsets7,8 (Fig. 20–1). ILCs do not somatically recombine the genes encoding the antigen-specific TCR and unlike adaptive lymphocytes are epigenetically poised to rapidly transcribe and produce cytokines when activated through cytokine receptors ...

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