Bronchus-associated lymphoid tissue (BALT) was originally described as a mucosal lymphoid organ in the lungs of some species. However, while the lungs of naive mice and humans typically lack BALT, pulmonary infection in mice leads to the development of inducible BALT (iBALT), which is located in peribronchial, perivascular, and interstitial areas throughout the lung. Here we investigated whether iBALT forms in patients with a variety of interstitial lung diseases. We show that while iBALT can be found in the lungs of patients suffering from multiple diseases, well-developed iBALT is most prevalent in patients with pulmonary complications of RA and Sjogren syndrome. In these patients, iBALT consisted of numerous B cell follicles containing germinal centers and follicular dendritic cells. A loosely defined T cell area surrounded the B cell follicles while lymphatics and high endothelial venules were found at the B cell/T cell interface. Increased expression of lymphoid-organizing chemokines, such as CXCL13 and CCL21, as well as molecules involved in the immunopathology of RA, such as B cell–activating factor of the TNF family (BAFF), ICOS ligand, and lymphotoxin, correlated with more well-developed iBALT. Finally, the presence of iBALT correlated with tissue damage in the lungs of RA patients, suggesting that iBALT participates in local RA pathogenesis.

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Inducible bronchus-associated lymphoid tissue (iBALT) in patients with pulmonary complications of rheumatoid arthritis

M cells are specialized epithelial cells of the mucosa-associated lymphoid tissues. A characteristic of M cells is that they transport antigens from the lumen to cells of the immune system, thereby initiating an immune response or tolerance. Soluble macromolecules, small particles, and also entire microorganisms are transported by M cells. The interactions of these substances with the M cell surface, their transcytosis, and the role of associated lymphoid cells are reviewed in detail. The ultrastructure and several immuno- and lectin-histochemical properties of M cells vary according to species and location along the intestine. We present updated reports on these variations, on identification markers, and on the origin and differentiation of M cells. The immunological significance of M cells and their functional relationship to lymphocytes and antigenpresenting cells are critically reviewed. The current knowledge on M cells in mucosa-associated lymphoid tissues outside the gut is briefly outlined. Clinical implications for drug deliver, infection, and vaccine development are discussed.

M cells in Peyer's patches of the intestine.

Bronchus-associated lymphoid tissue (BALT) is a constitutive mucosal lymphoid tissue adjacent to major airways in some mammalian species, including rats and rabbits, but not humans or mice. A related tissue, inducible BALT (iBALT), is an ectopic lymphoid tissue that is formed upon inflammation or infection in both mice and humans and can be found throughout the lung. Both BALT and iBALT acquire antigens from the airways and initiate local immune responses and maintain memory cells in the lungs. Here, we discuss the development and function of BALT and iBALT in the context of pulmonary immunity to infectious agents, tumors, and allergens as well as autoimmunity and inflammatory diseases of the lung.

/pdf/bronchus-associated-lymphoid-tissue-balt-structure-and-5b2r3642ps.pdf

Bronchus-associated lymphoid tissue (BALT) structure and function.

Tetanus toxoid was adsorbed onto poly(L-lactic acid) microspheres. Analyses by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and Western blotting suggest that the formulation procedure does not affect the stability or the antigenic properties of the protein. After nasal administration to guinea-pigs, the resulting preparation enhanced the immune response to the tetanus toxoid when compared with the free antigen. The increase in systemic immunoglobulin G titre was almost immediate in the group treated with the adsorbed tetanus toxoid (time zero, 140; week 2, 1550; week 4, 2760), reaching 36,000 two weeks after the booster (week 7), whereas the free antigen produced an immune response similar to that found in non-treated animals. In a parallel experiment, latex particles of a similar size to poly(L-lactic acid) microspheres, administered to both rats and rabbits, were detected in the blood stream. These findings with tetanus toxoid demonstrate the use of microsphere delivery systems for nasal application of antigens. These had a profound effect on the immune response, and indicate possibilities for overcoming some of the barriers to drug absorption in general.

Immune response to nasal delivery of antigenically intact tetanus toxoid associated with poly(L-lactic acid) microspheres in rats, rabbits and guinea-pigs.

Only relatively recently the significance of inducing not only systemic immunity but also significant local immunity at susceptible mucosal surfaces has become appreciated. A new field of mucosal immunity has been established as information accumulates on mucosal-associated lymphoid tissue (MALT) and on its role in both local and systemic immune responses. This review describes the formulation of vaccines to be delivered to one of MALT components, i.e. the nasal-associated lymphoid tissue (NALT), which bears some similarities with the Peyer's patches of the intestine. The association of antigens with adjuvants and particulate carriers such as microparticles, nanoparticles and liposomes is emphasised.

Nasal Delivery of Vaccines

Soluble protein antigen (Horseradish peroxidase — HRP) administered to rats intratracheally is predominantly phagocytosed by alveolar macrophages and Type-II pneumonocytes. A proportion, after localization on the lumenal surface of the bronchiolar epithelium is transported across the epithelium via the apical cytoplasm and the intercellular space to the region of the basement membrane. The rate of transfer is faster in the epithelium closer to areas of BALT than elsewhere and in these areas there is further significant penetration below the basement membrane into the BALT tissue to facilitate the contact of antigen and of lymphoid cells. No evidence of alveolar macrophage re-entry to the lymphatic system after phagocytosis of HRP could be seen.

Nigel A. Edmondson

Papers

Preferential uptake of soluble antigen by respiratory tract epithelium overlying bronchus-associated lymphoid tissue in the rat.