Histology of the immune (lymphoid, lymphatic) system

1. Histology of the immune (lymphoid, lymphatic) system • Jeanne Adiwinata Pawitan • Dept. of Histology • FMUI Jeanne A Pawitan

2. Immune system • Cells of the immune system • Bone marrow (myeloid tissue) • Diffuse lymphoid system • Diffuse lymphoid tissue • Lymph (lymphoid) nodules • Lymphoid organs - capsule Jeanne A Pawitan

3. Immune system – defense mechanism • Function: protection >< foreign elements • Foreign macromolecules • Invasive microorganisms • Viruses • Bacteria • Others • Transformed cells Jeanne A Pawitan

4. Defence mechanism (Martini) • Non specific defenses • Physical barriers • Phagocytes (M, neutro, eosinophils, monocytes) • Immunological surveillance: NK cells • Interferons, complement system • Inflammatory responses, fever • Specific defenses – specific immunity –specific immune response • Innate (human >< animal disease, except AIDS) • Acquired Jeanne A Pawitan

5. Immune response • Specific recognition system (specific immune system) • Recognize self >< non self • Component • Cellular (lymphocytes B, T) • Soluble (Ig) • Nonspecific (innate) effector system (non specific immune system) • Amplifies – function – specific system Jeanne A Pawitan

6. Nonspecific immune system • Soluble component • Complement proteins (cytokines): lymphokines-monokines: interleukines (ILs), interferons (IFNs), tumor necrosis factors (TNFs), transforming growth factors (TGFs), hematopoietic colony-stimulating factors (CSFs) • Cellular component – phagocytes: • Blood: neutrophils, eosinophils, monocytes • Tissue: macrophages (alveolar macrophages, Kupffer’s cells, synovial cells – joint cavities, perivascular microglial cells – CNS) Jeanne A Pawitan

7. Bone marrow (red) – myeloid tissue • Location: • central (marrow, medullary) cavity – long bones • Interstices (trabeculae) – spongy/cancelous bones • Soft, gelatinous, highly vascular – cellular tissue • Function: hemopoiesis – 5th month prenatal • LM: • vascular compartment (A., V., sinusoids) • Intervening spaces • hemopoietic compartments – meshwork - islands of hemopoietic cells • Adventitial reticular cells, reticular fibers Jeanne A Pawitan

8. Bone marrow cells • Hemopoietic cells • Blood cells – various stages • Macrophages – destroyed • Nuclei – erythrocytes precursors • Malformed cells • Excess cytoplasm • Adventitial reticular cells • By age 20 – adult: cytoplasm - accumulate fat • ≈ adipose cells – large – reduce hemopoietic compartment •  yellow marrow Jeanne A Pawitan

9. Diffuse lymphoid system • Non-encapsulated • Location: • Lymphoid organs • Mucosa (lamina propria) – mucosa associated lymphoid tissue (MALT) • Digestive system (Gut ALT): Peyer’s patches • Respiratory system (Bronchus ALT) • Urinary system • Occur as • Diffuse lymphoid tissue = localized lymphocyte infiltration • Lymphoid nodules (lymphonodulus) Jeanne A Pawitan

10. Diffuse lymphoid tissue • Consists of • Stroma • Reticular fibers – silver impregnation • Reticular cells of mesenchymal origin – some are phagocytic ≈ fixed macrophages • Lymphocytes • Free macrophages • Plasma cells Jeanne A Pawitan

11. Reticular cells • Shape: elongate – stellate • Nucleus: ovoid – euchromatic • Cytoplasm: • Scanty • Acidophilic • Contains • RER – few • Golgi complex – moderate-well developed • Fine filaments – bundles – at periphery Jeanne A Pawitan

12. Lymph (lymphoid, lymphatic) nodule, lymphonodulus – lymphoid follicles • =circumscribed-spherical/ovoid-closely packed-lymphocytes • In diffuse lymphoid tissue • Location: • Lymph node –cortex • Spleen – white pulp • Tonsils • Lamina propria (MALT): Peyer’s patches, etc. Jeanne A Pawitan

13. Gut-associated lymphoid tissue • Isolated lymphoid follicles • Peyer’s patches – aggregates – ileum • Lymphoid follicles • B cells • T cells – looser – surrounding B Cells • Numerous APC – surrounding B cells • Simple columnar epithelium  M (microfold) cells – capture Ag  present their epitopes to lymphocytes • Afferent lymph vessels (-), • Efferent lymph drainage (+) • Received small arterioles  capillary bed  high endothelial lined venules (HEVs) • Lymphocytes entering Peyer’s patches have homing receptors – specific for HEVs of GALT Jeanne A Pawitan

14. Bronchus-associated lymphoid tissue • ≈ Peyer’s patches – walls – bronchus – esp. bronchi-bronchiole bifurcate • Epithelial cover: pseudostratified ciliated columnar epithelium with goblet cells  M cells • Afferent lymph vessels (-) • Efferent lymph drainage (+) • Rich vascular supply  HEVs • Possible systemic and localized role in immune response • Lymphocytes entering BALT have homing receptors for HEVs of BALT • Cells: mostly B cells, also APC, T cells Jeanne A Pawitan

15. Lymphoid organs • Thymus (primary lymphoid organ) • Lymph nodes (lymphonodus) • Spleen (lien) • Tonsils (tonsila) Jeanne A Pawitan

16. Thymus • Location: superior mediatinum – anterior of great vessels (aorta) • After puberty – involution (atrophy) → adult – adipose cells • 2 lobes • Encapsulated – dense-irregular-collagenous connective tissue septa (trabecula) – lobes  incomplete lobules Jeanne A Pawitan

17. Lymph node • Location: interposed in the path of lymph vessels-esp. • Neck, axila, groin • Along major vessel • body cavities • Functions: • Filter – remove • Bacteria • Foreign substances Jeanne A Pawitan

18. Lymph node • Small, soft, Ø < 3 cm • Capsule – fibrous connective tissue (thickened at hilum) - trabeculae - adipose tissue • Convex: afferent lymph vessels – valves • Concave = hilum: A., V., efferent lymph vessels – valves  ← medulla Jeanne A Pawitan

19. Lymph node - sinuses Sinuses: network – stellate reticular cells – macrophages – endothelial-like simple squamous epithelium – migratory lymphoid cells Course: Afferent lymphatic vessels • Subcapsular sinus • Cortical (paratrabecular) sinuses • Medullary sinuses Efferent lymphatic vessels Jeanne A Pawitan

20. Lymph node • Histologically: • Cortex – antigen-presenting follicular dendritic cells • Primary lymphoid nodules (virgin B & memory B cells) • Secondary nodules (with germinal centers) – antigenic challenge B memory & plasma cell • Paracortex – Thymus dependent zone • Medulla Jeanne A Pawitan

21. Lymph node - medulla • Trabeculae – from hilum • Medullary cords • Network – reticular fiber – reticular cells • Cells • Lymphocytes – migrating from cortex  medullary sinuses • Plasma cells • Macrophages Jeanne A Pawitan

22. Lymph node - vascularization • Artery (hilum)  trabeculae  medulla  medullary cords  • Capillary beds in medulla • Cortex – cortical capillary beds  postcapillary venules (paracortex)  vein - hilum Jeanne A Pawitan

23. Spleen (lien) • Largest lymphoid organ • Upper left quadrant – abdominal cavity • Intraperitoneal – visceral peritoneum • Function: • Proliferation B, T cells • Ab formation – blood-borne Ag inactivation • Elimination of Ag, bacteria, particles, etc. • Filtering blood – destroying old erythrocytes • Hemopoietic (fetal) – adult – when needed Jeanne A Pawitan

24. Spleen (lien) • Convex surface • Concave surface – hilum – capsule-thickened • Arteries – nerve fibers (in) • Veins – lymph vessels (out) • Dense – irregular connective tissue – capsule - occasional smooth muscle cells – trabeculae  into the organ Jeanne A Pawitan

25. Spleen (lien) • Histology • Network – reticular fibers – reticular cells – attached to capsule  trabeculae – blood vessels • Fresh - cut - parenchyma • Grey area = white pulp • (Marginal zone – 100 μm wide – between white – red pulp) • Surrounding red area = red pulp (splenic cords of Billroth) Jeanne A Pawitan

26. Spleen (lien) – blood supply • Splenic artery - hilum branching  trabecular arteries ( 0.2mm) central arteries – periarterial lymphatic sheath (PALS)  • Radiating - slender blood vessels  red pulp  (recur) -marginal sinuses – marginal zone • branching penicillar arteries – red pulp: • Pulp arteriole • Sheated arteriole – Schweigger-Seidel sheath – macrophages) • Terminal arterial capillaries – splenic sinuses  • Veins of the pulp  splenic vein portal vein Jeanne A Pawitan

27. Closed circulation – open circ. • Closed circulation • Endothelial lining: terminal arterial capillaries –continuous - sinuses • Open circulation • Terminal arterial capillaries – red pulp - sinuses • Combination of both Jeanne A Pawitan

28. Spleen (lien) – white pulp • Central arteriole • PALS: • T lymphocytes • Frequently: lymphoid nodules (B cells) – germinal center = antigenic challenge  central arteriole - periphery Jeanne A Pawitan

29. Spleen (lien) – red pulp •  sponge • Spaces = splenic (venous) sinuses (sinusoids) • Endothelial lining – fusiform  staves of a barrel • Between endothelial cells - spaces - 2-3 m • Surrounded by reticular fibers (continuous with splenic cords) – thin strands ┴ longitudinal axis • Have a discontinuous basal lamina • Sponge material = splenic cords of Billroth • Reticular fibers (collagen III) – loose network – interstices permeated by extravasated blood • Stellate reticular cells – isolate coll III from blood >< platelet reaction to coll >< coagulation • Macrophages particularly numerous near sinusoids Jeanne A Pawitan

30. Spleen –histophysiology • Macrophages • Marginal sinuses – macrophage rich • Periphery of splenic sinuses • Phagocytosis • Ag, bacteria, particulate matter, etc • Old erythrocytes • Less fkexible (old, malaria) –cannot penetrate spaces between endothelium • Surface coat: sialic acid residue (-)  galactose moieties exposed – induced phagocytosis Jeanne A Pawitan

31. Spleen –histophysiology • Lymphocytes -Ag challenge  white pulp  • B memory cells, plasma cells – lymphoid nodules • T cells (various subcategories) – PALS •  marginal sinuses  • Site of Ag challenge • Circulating pool of lymphocytes • Plasma cells • Some  stay in marginal zone  Ab marginal sinuses • Most  bone marrow – Ab  bone marrow sinuses Jeanne A Pawitan

32. Tonsils: palatine, pharyngeal, lingual • Incompletely encapsulated • Aggregates of lymphoid nodules • Guard the entrance of oral (oro) pharynx • Exposed to • Airborne Ag • Ingested Ag • Reaction to Ag • Forming lymphocytes • Mounting immune response Jeanne A Pawitan