Leukocyte Homing Within Secondary Lymphoid Organs

Acquired immunity is perhaps the most significant evolutionary advancement of the vertebrate immune system. This system is dependent on the ability of circulating lymphocytes to migrate from the periphery to secondary lymphoid organs such as the lymph nodes, Peyer's patches, and spleen [127,128], Constant circulation of lymphocytes through the lymphoid and circulatory systems provides an effective means to present captured foreign antigen to the lymphocyte repertoire. Homeostatic chemokines are largely responsible for regulating this aspect of acquired immunity.

During inflammation, chemokine release at the area of insult rapidly recruits tissue resident dendritic cells expressing CCR1, CCR5, CCR6, and CXCR1 chemokine receptors [127], After antigen capture and dendritic cell stimulation, the profile of expressed chemokine receptors changes dramatically. The inflammatory receptors are downregulated and the homeostatic receptors CCR7, CXCR4, and CCR4 are upregulated [129], This serves both to remove the chemotactic pressure to remain in the area of inflammation as well as to target the antigen-loaded dendritic cells to the draining lymph nodes.

Homing of both dendritic cells and T cells to secondary lymph nodes appears to be largely dependent on the CCR7 chemokine receptor. Mice possessing the paucity of lymph node T cells (pit) mutation—where T cell and dendritic cell migration to lymph nodes and splenic white pulps is impaired—show a defect in the expression of CCL21/SLC, the ligand of CCR7 [130], In addition, CCR7 deficient mice exhibit severe defects in dendritic cell and T cell trafficking to lymph nodes and node microarchitecture. These mice also fail to mount primary T cell responses [125], CCR7 has been identified as regulating the migration of CD4+ Thl cells to the T cell zone of secondary lymphoid organs [131]. Conversely, gene transfer of CCR7 to CD4+ Th2 cells changed their localization from the splenic B cell zone to the peri arteriolar lymphoid sheath (PALS) and severely impaired the B cell response to antigen [131]. Forster et al. [125] also demonstrated that non-primed CCR7' show inappropriate B cell stimulation, due to altered migration of T and B cells to PALS and B cell follicles, and that immunized CCR77 mice display delayed primary IgG isotype switching.

B cell trafficking is also highly dependent on chemokine expression. The means by which CXCL13/BLC and CXCR5 influence B cell function have been extensively studied. Mice deficient in CXCR5 or its ligand CXCL13/BLC both exhibit a severe developmental phenotype lacking most lymph nodes and Peyer's patches [132,133]. Furthermore, CXCL13 mice lack conventional B cell follicles in the lymph nodes and spleen and have defects in immigration of follicular dendritic cells [132]. CXCR4 ' B cells are capable of trafficking to lymphoid compartments, but ligand-induced desensitization of CXCR4 and CCR7 strongly inhibits B cell homing [134],

In summary, chemokines and their receptors are critical for trafficking of leukocytes for the process of antigen gathering. Furthermore, they contribute substantially to the organization of secondary lymphoid tissues, helping to dictate the various compartments within them.

Natural Treatments For Psoriasis

Natural Treatments For Psoriasis

Do You Suffer From the Itching and Scaling of Psoriasis? Or the Chronic Agony of Psoriatic Arthritis? If so you are not ALONE! A whopping three percent of the world’s populations suffer from either condition! An incredible 56 million working hours are lost every year by psoriasis sufferers according to the National Psoriasis Foundation.

Get My Free Ebook

Post a comment