Primary Lymphoid Organs (B/T cell maturation):
• Bone marrow — B-cells (mammals).
• Thymus — T-cells. Has cortex (dense lymphocytes) + medulla (lighter, with Hassall's corpuscles).
• Bursa of Fabricius — B-cells in birds.

Secondary Lymphoid Organs (immune response):
• Lymph node — bean-shaped; cortex (B-cell follicles) + paracortex (T-cells) + medulla (medullary cords + sinuses).
• Spleen — white pulp (lymphoid; B-cell follicles + PALS = T-cells around central artery) + red pulp (sinusoids + cords).
• Tonsils — pharyngeal mucosal lymphoid tissue; with crypts.
• MALT (Peyer's patches, BALT, GALT).

LYMPHOID SYSTEM HISTOLOGY

I. PRIMARY LYMPHOID ORGANS (where lymphocytes are MADE & mature):

1. Bone Marrow: Site of all blood cell production; B-cell maturation in mammals.

2. Thymus:
• Lobed organ whose cervical and mediastinal extent varies markedly among domestic species and with age; it is large in young animals, atrophies after puberty.
• Capsule + trabeculae divide it into lobules.
• Cortex: densely packed immature T-cells (thymocytes); few visible epithelial cells. T cells undergo positive selection mainly in the cortex; negative selection occurs chiefly in the medulla and corticomedullary region.
• Medulla: lighter; mature T-cells; Hassall's corpuscles = whorls of degenerated epithelial cells (PATHOGNOMONIC for thymus on histology).
• Blood-thymus barrier (cortex only) prevents auto-antigen exposure.

3. Bursa of Fabricius (Birds): Sac-like dorsal diverticulum of cloaca; B-cell maturation. Atrophies after sexual maturity.

II. SECONDARY LYMPHOID ORGANS (where antigens are PROCESSED & immune responses occur):

1. Lymph Node:
• Capsule + trabeculae.
• Cortex (outer):
– Lymphoid follicles: round dense aggregates of B-cells.
• Primary follicles = quiescent.
• Secondary follicles = active; have germinal center (pale, with proliferating B-cells, follicular dendritic cells, helper T-cells).
– Subcapsular sinus with macrophages.
• Paracortex (deep cortex): T-cells; high endothelial venules (HEV) — lymphocytes enter from blood here.
• Medulla: Medullary cords (plasma cells + macrophages) + medullary sinuses (drainage).
• Lymph flow: afferent lymphatics (multiple) → subcapsular sinus → trabecular sinuses → medullary sinuses → efferent lymphatic (one) at hilum.

2. Spleen:
• Capsule with smooth muscle (especially in horse + dog → can contract to release stored RBCs).
• Trabeculae carry vessels.
• White pulp = lymphoid tissue:
– PALS (Periarteriolar lymphoid sheath) around central arteriole = T-cells.
– Lymphoid follicles (often eccentric on PALS) = B-cells; active ones have germinal centers.
• Red pulp = blood-filled tissue:
– Splenic cords (of Billroth) = reticular meshwork + macrophages + RBCs + plasma cells.
– Sinusoids = elongated venous spaces with discontinuous endothelium; macrophages screen passing RBCs (remove old/damaged).
• Marginal zone between white + red pulp; contains specialised macrophages.
• Function: blood filtration, RBC storage (huge in horse), immune surveillance.

3. Tonsils:
• Mucosal lymphoid aggregates around oropharynx (palatine, lingual, pharyngeal).
• Tonsillar epithelium and crypt development vary by site: oropharyngeal tonsils are generally stratified squamous, whereas the pharyngeal tonsil has respiratory epithelium.
• Lymphoid follicles deep to crypts.

4. MALT (Mucosa-associated Lymphoid Tissue):
• GALT = Gut: Peyer's patches in ileum (clusters of lymphoid follicles in submucosa); covered by M-cells (sample antigens).
• BALT = Bronchus.
• NALT = Nasopharyngeal.
• Diffuse lymphocytes throughout lamina propria.