Gut-associated lymphoid tissue

Owing to its physiological function in food absorption, the mucosal surface is thin and acts as a permeable barrier to the interior of the body.

Equally, its fragility and permeability creates vulnerability to infection and, in fact, the vast majority of the infectious agents invading the human body use this route.

These are located at the bottom of the crypts and release a number of antibacterial substances, among them lysozyme, and are thought to be involved in the control of infections.

[11] The development of the GALT has also been described in several marsupial species,[12] including tammar wallabies,[13] stripe-faced dunnarts (Sminthopsis macroura),[14][15] and red-tailed phascogales [16] The Peyer's patch is an aggregate of lymphoid cells projected to the lumen of the gut which acts as a very important site for the initiation of the immune response.

The complex interaction between these intestinal microbiota, the intestinal epithelial layer, and the local mucosal immune system is essential for maintaining gut health and systemic immunity because the nutrition level of a person’s diet contributes to the gut microbiota (a multispecies microbial community of bacteria, fungi, and viruses, all in a particular niche) that is in synergy with the host.

[5] Still there must be a robust defence in a case that pathogens cross either the border line of epithelium or produce harmful substances like bacterial toxins.

Firstly epithelial cell binds a dimer of IgA via polymeric Ig receptor at the basolateral side and transports it in a vesicle into the luminal space.

Inappropriate stimulation (typically by segmented filamentous bacteria - SFB) of chronic Th1 or Th17 cell response plays a crucial role in pathological damage to the host.

[23] Robust engagement of a variety of lymphoid cells patrolling the epithelial layer also reflects evolutionary pressure and arms race between immune systems and pathogens escaping its control.

[24] In contrast to other peripheral lymphocytes, IEL do not circulate in the blood stream or lymphatic system but reside in the epithelial layer in intestine.

[24] γδ T cells express TCR receptor made of γ and δ subunit and do not recognize antigen peptides presented in the MHC-bound form.

Main property of γδ T cells is formation of long-lived memory populations in barrier tissues such as intestinal epithelium or in the skin.

Macrophages can use their trans-epithelial dendrites (long cytoplasmic extensions) and directly contact epithelial layer and sample luminal bacteria.

[26] Under healthy conditions macrophages engulf commensal bacteria and surrounding cellular debris, secrete IL-10, drive maturation of Treg and contribute to tissue homeostasis.

Because of low expression of innate response receptors and co-stimulatory surface molecules, intestinal macrophages do not initiate inflammation.

But upon infection or inflammation, the profile of macrophages changes and they start to secrete large amounts of TNF-α and become proinflammatory effector cells.

Inherent production of retinoic acid and TGF-β (typical for gut-associated DCs) induces expression of gut-homing molecules and favor IgA switch during maturation of B cells in folicules.

DCs also direct Treg and conventional IELs to receive their final phenotype of mature effector cells in intestine.

It has been suggested that from this existing GALT, and due to the pressure put by commensal bacteria in gut that coevolved with vertebrates, later specializations as thymus, spleen or lymph nodes appeared as part of the adaptive immune system.