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# Innate-like lymphocytes: ILCs, γδ T, NKT, MAIT, B-1 and marginal-zone B cells

- Cell

Some lymphocytes do not wait days to learn: they react within hours to common danger signals and act as a bridge between innate and adaptive immunity.

Updated 2026-11-01

## Key points

- ILCs = innate mirror of Th1, Th2 and Th17, with no antigen receptor.
- γδ T cells live in epithelia and are not MHC-restricted.
- NKT cells see lipids on CD1d; MAIT cells see bacterial vitamin B metabolites on MR1.
- Marginal-zone B cells answer blood-borne polysaccharides: why the spleen protects against encapsulated bacteria.
- ILC2 + IL-5/IL-13 = helminths and allergic asthma.

## What it is

Besides classic T and B cells with highly diverse receptors, the body has lymphocytes with no antigen receptor (innate lymphoid cells, ILCs) or with receptors of limited diversity (γδ T cells, NKT cells, MAIT cells, B-1 and marginal-zone B cells). They sit mainly in epithelia, mucosa, liver, body cavities and the spleen, and respond fast to cytokines or to conserved microbial molecules. They give early protection and shape the later adaptive response.

## Key facts

- ILCs have no T- or B-cell receptor and do not need RAG; they mirror the helper T subsets (ILC1 like Th1, ILC2 like Th2, ILC3 like Th17).
- Their master transcription factors match the T-cell subsets: T-bet (ILC1), GATA-3 (ILC2), RORγt (ILC3).
- MAIT cells are a small fraction of blood T cells but a large share of T cells in the liver.
- The splenic marginal zone matures slowly, one reason why children under 2 years respond poorly to pure polysaccharide antigens.
- Conjugate vaccines link the polysaccharide to a protein so that helper T cells drive a stronger, longer-lasting response.

## Innate-like lymphocytes at a glance

| Cell | What it recognises | Where | Main role |
| --- | --- | --- | --- |
| ILC1 (and NK cells) | No antigen receptor; activated by cytokines (IL-12, IL-15, IL-18) | Mucosa, liver; NK cells in blood | IFN-γ against intracellular microbes; NK cells kill infected and tumour cells |
| ILC2 | No antigen receptor; activated by epithelial alarmins (IL-25, IL-33, TSLP) | Lung, gut, skin | IL-5 and IL-13: defence against helminths; contributes to asthma and allergy |
| ILC3 (including LTi cells) | No antigen receptor; activated by IL-1β and IL-23 | Gut lamina propria | IL-17 and IL-22: mucosal barrier against bacteria and fungi; LTi cells build lymph nodes in the fetus |
| γδ T cells | Limited TCR; stress molecules and non-peptide antigens, not MHC-restricted | Skin and intestinal epithelium | Rapid cytokines and killing of stressed epithelial cells |
| NKT cells | Semi-invariant αβ TCR; lipids presented by CD1d | Liver, spleen | Fast IFN-γ or IL-4; response to lipid antigens |
| MAIT cells | Semi-invariant αβ TCR; bacterial vitamin B (riboflavin) metabolites on MR1 | Liver, mucosa, blood | Rapid response to many bacteria and yeasts |
| B-1 and marginal-zone B cells | Limited BCR; polysaccharides and lipids (T-independent) | Peritoneal and pleural cavities (B-1); splenic marginal zone | Natural IgM and quick IgM against blood-borne encapsulated bacteria |

## Markers

- NK: CD16, CD56
- ILC: lineage-negative, CD127
- γδ TCR
- NKT: CD1d
- MAIT: MR1
- B-1: CD5

## Clinical notes

- Asplenia or splenectomy removes marginal-zone B cells: risk of overwhelming infection by pneumococcus, Haemophilus and meningococcus.
- ILC2s activated by IL-33 and TSLP help sustain eosinophilic asthma, a target of anti-alarmin biologics.
- Many of these cells are kept even in RAG-deficient SCID (ILCs and NK cells), which explains the T-B-NK+ phenotype.
- B-1 cells produce natural IgM against conserved molecules such as phosphorylcholine, part of early protection against pneumococcus.

## Memory aid

ILC1, 2 and 3 are the T helpers without an ID card: they do the same jobs (IFN-γ, IL-5/IL-13, IL-17/IL-22) but nobody checked which antigen they know.

## Test yourself

Think of the answer, then tap the question to see it.

## Which innate lymphoid cell group responds to IL-33 and makes IL-5 and IL-13?

ILC2, important against helminths and in allergic asthma.

## Which molecule presents lipid antigens to NKT cells?

CD1d, a non-polymorphic MHC class I-like molecule.

## Why does asplenia raise the risk of infection by encapsulated bacteria?

It removes marginal-zone B cells and splenic macrophages that make fast IgM against blood-borne polysaccharides and clear opsonised bacteria.

## What do MAIT cells recognise?

Vitamin B (riboflavin) metabolites made by bacteria and yeasts, presented by MR1.

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## Related

- [Natural killer cell](https://durgical.com/en/immunology/natural-killer-cell/)
- [B cell and plasma cell](https://durgical.com/en/immunology/b-cell-and-plasma-cell/)
- [Th1, Th2, Th17, Tfh and Treg](https://durgical.com/en/immunology/th1-th2-th17-tfh-and-treg/)
- [Spleen: white pulp, red pulp, asplenia](https://durgical.com/en/immunology/spleen-white-pulp-red-pulp-asplenia/)
- [Interleukin-17](https://durgical.com/en/immunology/interleukin-17/)
- [IL-4, IL-5 and IL-13 (the Th2 cytokines)](https://durgical.com/en/immunology/il-4-il-5-and-il-13/)
- [Innate immunity (overview, barriers)](https://durgical.com/en/immunology/innate-immunity/)

[← All of immunology](https://durgical.com/en/immunology/)

Educational content on the immune system; not a treatment or individual vaccination guide and no substitute for a health professional's advice. No doses are given.

Sources: [21.2 Barrier Defenses and the Innate Immune Response](https://openstax.org/books/anatomy-and-physiology-2e/pages/21-2-barrier-defenses-and-the-innate-immune-response) (OpenStax (Anatomy and Physiology 2e), 2022); [18.4 B Lymphocytes and Humoral Immunity](https://openstax.org/books/microbiology/pages/18-4-b-lymphocytes-and-humoral-immunity) (OpenStax (Microbiology), 2016).

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Representative model, for educational purposes only.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/immunology/innate-like-lymphocytes-ilcs-t-nkt-mait-b-1-and-marginal-zone-b-cells/