https://www.biosyn.com/Images/ArticleImages/DDT_Oct_2_2003_reprint.pdf

Vaccine adjuvants: role and mechanisms of action in vaccine immunogenicity.

The conjunctiva forms a continuous mucosal surface from the eyelid margin to the cornea, and makes contact with airborne antigens and those on the adjacent eyelid skin and preocular tear film. Conjunctival lymphoid follicles (CLF) undergo hyperplasia upon conjunctival infection by a specific array of pathogens; infection-associated enlargement of draining preauricular lymph nodes suggests that CLF participate in the afferent limb of acquired immune responses for the ocular surface. In this review, we examine the evidence for classification of CLF as part of the common mucosal immune system, and explore the possible therapeutic implications.

The conjunctival lymphoid follicle in mucosal immunology.

The mammalian immune system is an integrated network of tissue, leukocytes and effector and regulatory molecules. All these components operate i) to maintain the proper structure of and processes expressed by each tissue. and ii) to protect the hosts from those microorganisms that generally invade them as part of their life cycle. Among the invading microorganisms. Listeria monocytogenes (L. monocytogenes) can persist as a live organism independent of the host, and is, thus, able to drive short-term infectious and pathogenic processes that are controlled by integrated innate and adaptive protective immune responses driven by CD8 and CD4 type 1 T lymphocytes acting on non-T non-B leukocytes. Although the effector functions and the fine specificity of T lymphocytes have been more and more characterized, an understanding of the precise regulation of both leukocyte traffic and T-lymphocyte migration depends on knowledge of the early tissue distribution of L. monocytogenes, points that are addressed in this review.

Listeria monocytogenes in laboratory mice: a model of short‐term infectious and pathogenic processes controllable by regulated protective immune responses

For maintenance of immunity and tolerance, the organs and tissues of the organism are connected by migrating lymphoid cells. Understanding lymphocyte migration is essential for many disorders and diseases-- especially in the mucosa-lined organs. Detailed analyses of migrating lymphocytes have been performed in many species, especially in laboratory animals. However, important experiments in lymphocyte migration have been carried out in large animals, for example sheep, cattle and pigs. These species allow experimental procedures like in situ-organ labelling, lymphocyte retransfusion studies or lymph vessel cannulations. Such studies have made an important contribution to the understanding of the overall principles of lymphocyte migration especially in the mucosal immune system. Major results on the specific migration of naive and memory T cells through lymphoid organs, the re-distribution of gamma/delta T cells in the intestinal immune system and the emigration of newly produced B cells from the ileal Peyer's patches have been obtained in large animals. Since there are growing numbers of markers for large animals, and molecular biology methods are available in these species, experiments in large animals will be an essential tool for the understanding of lymphocyte migration especially in mucosal organs.

/pdf/lymphocyte-migration-studies-507nkzu91c.pdf

Lymphocyte migration studies.

The basolateral membranes of intestinal M cells are invaginated to form large intraepithelial "pockets" that are populated by specific sub-sets of mucosal leukocytes, including CD4+ T cells, memory and naive B cells, and occasional dendritic cells. The adhesion molecules involved in leukocyte trafficking and/or retention within this unique immunological niche are unknown. In this study, we used immunofluorescence microscopy and a battery of monoclonal antibodies to identify the adhesion molecules expressed by leukocytes situated within the intracellular pockets of mouse Peyer's patch (PP) M cells. M cell associated leukocytes (MAL) consistently stained positive for integrin alpha4beta7, and integrin LFA-1 (CD11a/CD18), but were rarely positive for L-selectin (CD62L) or the mucosal integrin alphaEbeta7. However, neither the alpha4beta7 ligands MadCAM-1 or VCAM-1, nor the LFA-1 ligand ICAM-1, were detected on M cell basolateral membranes. To determine whether integrins alpha4beta7 or LFA-1 play a functional role leukocyte homing to M cell pockets, we examined M cells in mice deficient in integrin beta7 or CD11a/CD18. Although PP from CD18 or integrin beta7 mice were reduced in number and size as compared to age-matched controls, we identified M cells in both strains of mice. However, mice lacking CD18 (but not integrin beta7) had significantly fewer leukocytes within M cell pockets as compared to control animals, suggesting LFA-1 (but not alpha4beta7) may contribute, in part, to leukocyte trafficking into and/or retention within this unique immunological niche.

Analysis of Adhesion Molecules Involved in Leukocyte Homing into the Basolateral Pockets of Mouse Peyer's Patch M Cells

When an antigen has passed the epithelial barrier of the skin or mucosal surfaces it has to be processed and presented by accessory cells to lymphocytes. These reactions take place in lymphoid organs, such as the regional lymph nodes, Peyer's patches and tonsils, but also in the spleen if the antigen entered the blood directly. The respective lymphocyte clone expands by proliferating, and primed lymphocytes of the B and T cell series emigrate from the lymphoid organs. The traffic of lymphocytes is regulated by the interaction of a series of adhesion molecules with endothelial cells and lymphocytes. Several earlier ideas, for instance one specific "homing receptor" for each organ and different receptors for B and T lymphocytes, or exclusive migratory routes for "memory" and "naive" lymphocytes, have had to be replaced by the concept of a much more complex, multistep, cascade-type reaction. Most migration routes show "preference" rather than "selectivity". The regulation of the entry of activated T and B lymphocytes into the parenchyma of non-lymphoid organs, e.g. the lamina propria of the gut, is not as well as understood as the entry into a lymph node. A further important aspect in lymphocyte traffic is the regulation of lymphocyte migration within the organs, including the interaction between lymphoid cells and the extracellular matrix. the basic mechanisms of lymphocyte migration have to be considered when the effects of vaccination procedures are interpreted.

Lymphocyte migration: an essential step in understanding the effects of vaccination.

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Lymphocyte migration: an essential step in understanding the effects of vaccination.