Mucosa-associated lymphoid tissue (MALT)

Also known as: MALT, GALT, BALT, NALT, gut-associated lymphoid tissue, bronchus-associated lymphoid tissue, nasopharynx-associated lymphoid tissue, mucosal immune system

Unencapsulated lymphoid tissue in the mucosae of the gut, airways and urogenital tract — from scattered lymphocytes to organised follicles such as the tonsils, Peyer patches and appendix — specialised for producing secretory IgA and maintaining tolerance to harmless antigens.

Overview

Mucosal surfaces — far larger in area than the skin, and mostly intestinal — are the main portals of entry for pathogens, and they are protected by the largest immune compartment in the body. Organised MALT consists of lymphoid follicles beneath a specialised epithelium: in the gut (GALT) the Peyer patches, the appendix and thousands of isolated lymphoid follicles; in the nasopharynx (NALT) the tonsils of Waldeyer ring; and, less prominently in healthy adults, bronchus-associated tissue (BALT). Diffuse MALT comprises the lymphocytes, plasma cells, dendritic cells and macrophages scattered in the lamina propria, and the intraepithelial lymphocytes (mostly CD8⁺ and γδ T cells) between epithelial cells. The gut contains the majority of the body's lymphocytes and plasma cells.

MALT has no afferent lymphatics; antigen is sampled directly from the lumen by M (microfold) cells in the follicle-associated epithelium, by dendritic cells extending processes between epithelial cells, and through goblet-cell-associated passages. Lymphocytes primed in MALT acquire mucosal homing receptors (α4β7 integrin, CCR9 for the gut), leave through draining lymph nodes, circulate, and return to mucosal lamina propria via MAdCAM-1 — and can seed other mucosae, including the lactating breast (the "common mucosal immune system").

The signature product is secretory IgA. Lamina-propria plasma cells secrete dimeric IgA (joined by a J chain), which binds the polymeric immunoglobulin receptor (pIgR) on the basolateral surface of epithelial cells, is transcytosed and released at the apical surface still attached to part of the receptor — the secretory component, which protects it from proteolysis. More IgA is made each day (several grams) than all other isotypes combined. It works by immune exclusion — neutralising toxins and microbes and preventing adherence — without triggering inflammation. MALT also maintains oral tolerance to food and commensal antigens through regulatory T cells.

Location

Lamina propria and submucosa of the gastrointestinal, respiratory, urogenital and conjunctival mucosae.

Parts & subdivisions

Gut-associated lymphoid tissue (GALT)

Peyer patches, appendix, isolated lymphoid follicles, lamina propria lymphocytes and intraepithelial lymphocytes.

Appendix

Rich in lymphoid follicles, especially in children and young adults — part of GALT.

Nasopharynx-associated lymphoid tissue (NALT)

The tonsils of Waldeyer ring.

Bronchus-associated lymphoid tissue (BALT)

Lymphoid aggregates at bronchial bifurcations; sparse in healthy adults, induced by infection or smoking.

M cells

Specialised epithelial cells with short microfolds instead of microvilli, a thin glycocalyx and a basolateral pocket holding lymphocytes and dendritic cells; they transcytose antigen intact.

Intraepithelial lymphocytes

Mostly CD8⁺ αβ and γδ T cells between epithelial cells; increased in coeliac disease.

Function

First-line adaptive defence of mucosal surfaces, principally via secretory IgA.

Sampling of luminal antigens to generate protective immunity against pathogens.

Maintenance of tolerance to food antigens and the commensal microbiota (oral tolerance).

Supplies IgA-secreting cells to exocrine glands, including the lactating mammary gland (breast-milk IgA).

Physiology

Class switching to IgA is promoted by TGF-β, retinoic acid (from gut dendritic cells), and BAFF/APRIL. Gut dendritic cells also imprint gut-homing receptors and favour induction of FOXP3⁺ regulatory T cells, helping explain why feeding an antigen usually induces tolerance rather than inflammation.

Clinical significance

MALT lymphoma

Extranodal marginal-zone B-cell lymphoma arising in MALT acquired through chronic antigen stimulation — most often gastric MALT lymphoma driven by Helicobacter pylori (early lesions often regress after eradication therapy), also salivary MALT lymphoma in Sjögren syndrome and thyroid MALT lymphoma in Hashimoto thyroiditis.

Mucosal immune disorders

Selective IgA deficiency (recurrent sinopulmonary and GI infections, giardiasis, coeliac disease, anaphylaxis to IgA in blood products); coeliac disease (gluten-reactive HLA-DQ2/DQ8-restricted T cells, raised intraepithelial lymphocytes, villous atrophy); inflammatory bowel disease, treated in part by blocking lymphocyte gut homing (vedolizumab, anti-α4β7).