ABSTRACT

Immune System and Importance of Compartmental Analysis of Lymphoid Organs ........... 518 14.3 Thymus ................................................................................................................................. 520

14.3.1 Thymus Structure: Historical Perspective .............................................................. 520 14.3.2 Thymus Structure: Species Differences ................................................................. 521 14.3.3 Thymus: Growth and Development ........................................................................ 522 14.3.4 Thymus: Function ................................................................................................... 524 14.3.5 Thymus: Conundrum of Involution versus Pathobiology ....................................... 525

14.4 Spleen .................................................................................................................................... 527 14.4.1 Spleen: Historical Perspective ................................................................................ 527 14.4.2 Spleen: White Pulp ................................................................................................. 528

14.4.2.1 PALS and Lymphoid Follicles ................................................................. 528 14.4.2.2 Marginal Zone, Mantle Zone, and Marginal Sinus .................................. 528

14.4.3 Spleen: Red Pulp ..................................................................................................... 531 14.4.3.1 Blood Flow and Filtration ........................................................................ 531

14.4.4 Spleen: Structure Recapitulates Function ............................................................... 531 14.4.4.1 Defensive Spleen ...................................................................................... 531 14.4.4.2 Storage Spleen .......................................................................................... 532 14.4.4.3 Intermediate Spleen .................................................................................. 532 14.4.4.4 Hematopoiesis .......................................................................................... 532 14.4.4.5 Lymphopoiesis .......................................................................................... 532

14.4.5 Spleen: Histopathology ........................................................................................... 533 14.5 Lymph Nodes ........................................................................................................................ 534

14.5.1 Lymph Nodes: Historical Perspective .................................................................... 534 14.5.2 Lymph Nodes: Structure and Species Differences ................................................. 535 14.5.3 Lymphoid Follicle: Functional Anatomical Dynamics .......................................... 538 14.5.4 Lymph Nodes: Histopathology ............................................................................... 538

14.6 Mucosal-Associated Lymphoid Tissue ................................................................................. 541 14.6.1 Bronchus-Associated Lymphoid Tissue.................................................................. 541 14.6.2 Nasal-Associated Lymphoid Tissue ........................................................................ 541 14.6.3 Gut-Associated Lymphoid Tissue ........................................................................... 542 14.6.4 GALT: Histopathology ........................................................................................... 543

14.7 Bone Marrow: Lymphopoiesis.............................................................................................. 545 14.8 Immunotoxicants versus Stress, the Hobgoblin of Toxicologic Pathology ..........................546 14.9 Lymphoid Neoplasia of Mice and Rats ................................................................................ 550

14.9.1 Small Lymphocyte: B-or T-Cell Origin ................................................................ 552 14.9.2 Follicular/Pleomorphic Lymphoma ........................................................................ 552 14.9.3 MZ Lymphoma ....................................................................................................... 552 14.9.4 Immunoblastic Lymphoma ..................................................................................... 552

Histomorphologic assessment of the immune system is a recognized cornerstone in the identication of immunotoxicity. Broad-based scientic forums have culminated in the generation of an International Conference on Harmonization (ICH) guidance and “Best Practices” for evaluation of the immune system (ICH S8 2006; Haley et al. 2005). Additionally, multiple excellent manuscripts and book chapters provide detailed methods to assist in the accurate and consistent characterization of intended and unintended drug-induced alterations of the immune system (Jones et al. 1990; Kuper et al. 1991, 1992, 1995; Greaves 2000; Gopinath et al. 1987; Sternberg 1997), and the reader is encouraged to obtain and regularly refer to these and the numerous excellent articles that are presented in the work of Maronpot (2006).