infections, and neoplasms (Figure 7.8). Immunohistochemistry can identify distinct T and B cell areas with high‐endothelial venules, follicles with follicular dendritic cells and sometimes germinal centers. The same cytokines and chemokines that orchestrate the formation of secondary lymphoid organs play a role, but tertiary lymphoid organs are formed after birth and not at preselected sites [33]. The role of tertiary lymphoid organs in inflammation and cancer is not well established. Tertiary lymphoid organs associated with autoimmune inflammation are thought to contribute to the autoimmune response and be detrimental. However, tertiary lymphoid organs formed in the adventitial layer of the aorta in ApoE‐deficient mice (B6.129P2‐Apoetm1Unc/J) with atherosclerosis seem to have a beneficial effect as the atherosclerosis was more severe in mice in which the formation of the serosal lymphoid tissue was blocked [60]. The presence of tertiary lymphoid organs in and near tumors is thought to increase the response to immunotherapy and to be a positive prognostic indicator [61].
Figure 7.7 Melanin vs. hemosiderin. (a) Spleen of B6.Cg‐Prkdcscid/SzJ mouse with melanocytes and melanin‐laden macrophages and hemosiderin. (b) Prussian blue stain distinguishes hemosiderin (blue) and melanin (dark brown) pigments.
Figure 7.8 Tertiary lymphoid structures. Tertiary lymphoid tissue with two follicles with germinal centers in the kidney of a CD‐1 mouse with chronic pyelonephritis.
Acknowledgments
This work was supported grants from the National Institutes of Health (R01‐CA089713 and P30‐CA034196 to JPS).
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