Unit 09 — Lymphoid Organs · Question Bank

The spleen is the largest secondary lymphoid organ and the body's only filter of the bloodstream. Unlike a lymph node it has no afferent lymphatics — blood arrives via the splenic artery, percolates through the parenchyma, and leaves via the splenic vein. To answer this essay fully you describe the connective-tissue framework (capsule and trabeculae), the lymphoid white pulp built around the central artery, the marginal zone that screens blood antigen, and the blood-filled red pulp that mechanically filters senescent erythrocytes. You should end with the relevant functional summary so the examiner sees you understand why each component looks the way it does.

Capsule & trabeculae

The spleen is enveloped externally by mesothelium (visceral peritoneum) which overlies a dense connective-tissue capsule that, uniquely among human lymphoid organs, contains scattered smooth-muscle cells. The capsule sends trabeculae deep into the parenchyma; these carry the trabecular arteries and veins and, in some species more than humans, contract to expel stored blood. There is no cortex–medulla organisation as in a lymph node, and there are no afferent lymphatics anywhere — an examiner-pleasing point because it underlines the spleen's status as a blood organ.

White pulp — PALS and splenic corpuscles

At the hilum the splenic artery branches into trabecular arteries, which eventually leave the trabeculae as small central arteries. Each central artery quickly becomes wrapped by a diffuse sleeve of T lymphocytes called the periarterial lymphatic sheath (PALS) — the splenic equivalent of the lymph-node paracortex. Off to one side of the PALS sits a splenic corpuscle: a B-cell nodule, primary or secondary with a germinal centre after antigenic stimulation, complete with follicular dendritic cells, centroblasts in the dark zone and centrocytes in the light zone. Together PALS + splenic corpuscle make up the white pulp, visible on H&E as violet islands set in the surrounding red.

Marginal zone

Between white and red pulp lies the marginal zone, a thin transitional layer populated by marginal-zone B cells, dendritic cells and macrophages. Side-branches of the central artery empty into a marginal sinus here, so any antigen carried in the blood is presented to the immune cells of the marginal zone before the blood enters the red pulp. This zone is the spleen's main sampling station for blood-borne antigen and is functionally indispensable for responses to encapsulated bacteria.

Red pulp — cords of Billroth and venous sinusoids

Beyond the marginal zone is the red pulp, which fills most of the splenic parenchyma. It is built of two interlocking elements. The splenic cords (cords of Billroth) are a loose meshwork of reticular cells, macrophages, plasma cells and stranded blood cells through which blood seeps in an open circulation. The venous sinusoids are wide vessels lined by rod-shaped “stave” endothelial cells with persistent slits between them and an incomplete, ring-like basal lamina. To return to circulation, a red cell must squeeze back from the cord into the sinus through these slits — only flexible cells succeed, and old or damaged erythrocytes are trapped in the cord and devoured by cordal macrophages.

Functional summary

The white pulp + marginal zone provide immune defence against blood-borne antigen, the red pulp filters blood by mechanically removing senescent or damaged erythrocytes (recycling their iron through cordal macrophages), and the spleen as a whole stores roughly a third of the body's platelet pool and serves as a reserve site of haemopoiesis in fetal life and severe stress. Splenectomy or sickle-cell autosplenectomy abolishes the marginal zone and red-pulp filtration, leaving the patient at lifelong risk of overwhelming infection by encapsulated organisms and producing Howell-Jolly bodies in the peripheral smear.

A lymph node is a bean-shaped secondary lymphoid organ placed along the lymphatic vessels of every drainage field. Its job is to filter lymph, mount adaptive immune responses against antigen carried in that lymph, and release antibody and effector lymphocytes into the efferent vessel. A full answer therefore needs a description of the connective-tissue framework, the three functional zones (superficial cortex, paracortex, medulla), and an explicit lymph pathway from afferent vessels to efferent vessel at the hilum.

Capsule, trabeculae, hilum

Each node is wrapped in a dense connective-tissue capsule from which trabeculae extend inward carrying blood vessels and dividing the cortex into incomplete compartments. The convex surface is pierced by several afferent lymphatics, each with a valve so that lymph flows only into the node, while the concave hilum on the opposite side is the exit point for a single (occasionally two) efferent lymphatic and for the blood vessels of the node. The whole parenchyma sits on a fine reticular scaffold of reticular cells and type-III collagen fibres.

Superficial cortex — the B-cell zone

Just deep to the subcapsular sinus, the superficial cortex contains spherical lymphoid nodules. Primary nodules are uniformly dark, populated by small resting B cells. Secondary nodules show a pale central germinal centre with a dark mantle; here antigen-activated B cells undergo proliferation, somatic hypermutation (dark zone, centroblasts) and selection against antigen held on follicular dendritic cells (light zone, centrocytes), eventually leaving as plasma cells or memory B cells. Between the nodules is internodular diffuse lymphoid tissue.

Paracortex — the T-cell zone

The deep cortex, or paracortex, is diffuse lymphoid tissue populated chiefly by T cells. It is called the thymus-dependent zone because it is colonised by mature T cells exported from the thymus, and it becomes empty in thymic aplasia such as DiGeorge syndrome. Its histological signature is the high endothelial venule (HEV) — a postcapillary venule with unusually tall cuboidal endothelium. Circulating naive lymphocytes use L-selectin and CCL21 to bind these HEVs and squeeze across into the node, which is how blood lymphocytes physically enter to look for antigen.

Medulla — cords and sinuses

Closer to the hilum the parenchyma reorganises into anastomosing medullary cords separated by wide medullary sinuses. The cords are strings of B cells, antibody-secreting plasma cells (which have migrated down from the germinal centres above), and macrophages embedded in reticular tissue. The medullary sinuses are lined incompletely by endothelium, are crossed by reticular fibres and resident macrophages, and pour antibody-rich filtered lymph toward the hilar efferent vessel.

Lymph pathway

Lymph flow follows the architecture directly. Afferent lymphatics empty into the subcapsular sinus just under the capsule; from there lymph passes through the peritrabecular (cortical) sinuses that run alongside the trabeculae down through the cortex, then through the medullary sinuses between the medullary cords, and finally exits at the hilum via the single efferent lymphatic. As it travels, macrophages lining the sinus walls phagocytose antigen, debris, and any tumour cells that have drifted in, while plasma cells in the cords add freshly made antibody to the stream.

The thymus is the primary lymphoid organ in which T lymphocytes complete their maturation and self-tolerance training. Two histological facts make it unique among the lymphoid organs: its stroma is built of epithelial reticular cells, not reticular connective tissue, and a true blood-thymus barrier in the cortex isolates developing thymocytes from circulating antigen. A complete answer describes the lobular architecture, the cellular population of cortex and medulla (with the diagnostic Hassall's corpuscles), the three components of the blood-thymus barrier, and notes the age-related involution that distinguishes the thymus from every other lymphoid organ.

Lobular architecture

A thin connective-tissue capsule covers the thymus and sends septa inward to divide it into incomplete lobules. Within each lobule a dark outer cortex and a paler central medulla can be made out, but the medulla of adjacent lobules is continuous so the demarcation is incomplete. The thymus is bilobed in the superior mediastinum and is largest at puberty before undergoing involution.

The stroma — epithelial reticular cells

Unlike every other lymphoid organ, the thymic framework is not reticular connective tissue but a meshwork of epithelial reticular cells. These are star-shaped epithelial cells joined to each other by desmosomes, leaving spaces in which thymocytes sit. They arise from endoderm of the third pharyngeal pouch in development — failure of this pouch in 22q11.2 deletion produces DiGeorge syndrome. Six subtypes of epithelial reticular cell are recognised; some form the capsular and septal lining, some constitute the blood-thymus barrier, some present self-antigen on MHC to test thymocytes, and some ultimately degenerate to form Hassall's corpuscles.

Cortex and medulla

The cortex is dark on H&E because it is densely packed with immature thymocytes — bone-marrow-derived precursors that arrive via blood and undergo positive then negative selection against self-MHC presented by the cortical epithelial reticular cells. Macrophages clear the apoptotic debris of the >95% that fail selection. The medulla is paler, contains fewer but more mature thymocytes (those that passed selection), abundant medullary epithelial reticular cells, dendritic cells and macrophages. Its diagnostic histological feature is the Hassall (thymic) corpuscle — a concentric onion-like whorl of degenerating, keratinised epithelial reticular cells found nowhere else in the body. The thymus has no B-cell nodules, no germinal centres, and no afferent lymphatics.

The blood-thymus barrier

The barrier exists only in the cortex and protects developing thymocytes from premature antigen exposure that would corrupt self-tolerance training. Three layers separate blood lumen from thymocyte. First, the continuous capillary endothelium with its basal lamina — tight junctions seal it, so molecules cannot leak between endothelial cells. Second, a perivascular space containing patrolling macrophages that phagocytose any antigen that does slip through. Third, a sheath of cortical epithelial reticular cells with their own basal lamina that physically separates the perivascular space from the parenchyma. Mature T cells leave the thymus via venules of the medulla, where no equivalent barrier exists.

Involution

The thymus is unique in being a regressing organ. It is largest in absolute size at puberty, after which its cortex thins and lymphoid tissue is progressively replaced by adipose tissue; Hassall's corpuscles persist as the most reliable clue that the residual tissue is still thymic. The clinical consequence is reduced output of naive T cells in older adults, which contributes to immune senescence.

Lymph node, spleen and thymus are the three named lymphoid organs of the body, but they differ in classification (primary vs secondary), in what they filter, in stromal scaffold, in regional architecture, and in what cells they contain. A clean comparison answer walks the examiner through each of these axes rather than describing the organs serially.

Classification and main function

The thymus is the only primary lymphoid organ of the three — its role is T-lymphocyte maturation and self-tolerance education, not the mounting of immune responses. Both lymph node and spleen are secondary lymphoid organs, sites where mature lymphocytes meet antigen and respond. The lymph node specialises in filtering lymph that drains from peripheral tissue beds; the spleen filters blood and additionally clears senescent erythrocytes.

Stroma

Lymph node and spleen share the standard lymphoid scaffold — reticular cells producing type-III collagen fibres, with lymphocytes packing the holes of the mesh. The thymus is unique: its stroma is built of epithelial reticular cells, star-shaped epithelial cells joined by desmosomes that are derived from endoderm of the third pharyngeal pouch. Recognising this single difference distinguishes thymus from any other lymphoid section on a slide.

Regional architecture

The lymph node has a clean three-zone plan: a superficial cortex of B-cell nodules, a paracortex of diffuse T-cell tissue with high endothelial venules, and a medulla of cords (plasma cells, B cells, macrophages) separated by medullary sinuses. The spleen has no cortex–medulla; instead, scattered white pulp (PALS of T cells around the central artery, plus a splenic corpuscle of B cells) sits within a sea of red pulp made of cords of Billroth and venous sinusoids, with a thin marginal zone between. The thymus has a lobular cortex (dark, thymocyte-packed, the site of selection) and medulla (pale, with Hassall's corpuscles).

Vascular and lymphatic supply

Only the lymph node has afferent lymphatics; spleen and thymus have none. Each lymph node has many afferents piercing the convex surface and a single efferent leaving at the hilum. The spleen receives blood at the hilum, channels it through trabecular arteries to central arteries surrounded by the PALS, and returns it via the splenic vein. The thymus has neither afferent lymphatics nor a special arterial arrangement; its critical vascular feature is the blood-thymus barrier in the cortex.

Cellular distinctives

Lymph node and spleen both contain B-cell follicles with germinal centres; the thymus contains no follicles and no germinal centres. The defining cell of the thymus is the epithelial reticular cell and its end-product, the Hassall corpuscle. The defining structure of the splenic red pulp is the rod-shaped stave cell of the venous sinusoid; of the splenic white pulp, the central artery wrapped by PALS. The lymph node's defining vessel is the high endothelial venule of the paracortex.

Life history

Finally, only the thymus involutes after puberty, with progressive replacement of lymphoid tissue by fat; lymph nodes and spleen are lifelong functioning organs that may enlarge in disease but do not regress with age.

The lymphoid nodule (follicle) is the basic structural unit of the B-cell response, and the germinal centre that arises at its core is where high-affinity, class-switched antibody is actually generated. A complete essay describes the primary and secondary nodule, the dark- and light-zone organisation of the germinal centre with its cell populations, the molecular events of proliferation, somatic hypermutation and selection, and the anatomical locations at which nodules are found.

Primary nodule

A primary lymphoid nodule is a spherical, 0.2–1 mm aggregate of small resting B lymphocytes with a clear boundary against surrounding diffuse lymphoid tissue. On H&E it is uniformly dark because the cells are small and tightly packed, and it lacks any pale central area. Primary nodules are seen in unstimulated lymphoid tissue or in immunodeficient subjects in whom germinal centres cannot form.

Secondary nodule and the germinal centre

Once a primary nodule encounters antigen and B cells become activated (with T-cell help from the adjacent paracortex / PALS), the nodule transforms into a secondary nodule with a pale central germinal centre surrounded by a dark rim called the mantle or corona of small, displaced resting B cells. The germinal centre itself organises into two anatomically and functionally distinct compartments. In the dark zone, large rapidly dividing centroblasts proliferate and undergo somatic hypermutation of their immunoglobulin V regions, generating clones with subtly altered receptors. In the light zone, smaller non-dividing centrocytes meet follicular dendritic cells (FDCs) whose long cytoplasmic processes retain antigen on their surface. Only centrocytes whose mutated receptor binds antigen with high affinity receive survival signals (with additional help from T follicular helper cells); the rest die by apoptosis and are phagocytosed by tingible-body macrophages, whose pale cytoplasm filled with dark apoptotic debris is the histological signature of a working germinal centre. Class switching of the immunoglobulin heavy chain also occurs here. Survivors exit as either antibody-secreting plasma cells or long-lived memory B cells.

Resident cell types

The cellular cast of a secondary nodule therefore includes (1) centroblasts of the dark zone, (2) centrocytes of the light zone, (3) follicular dendritic cells presenting antigen on their processes, (4) T follicular helper cells providing survival and class-switch signals, (5) tingible-body macrophages clearing apoptotic debris, and (6) small mantle-zone B cells around the periphery.

Locations

Lymphoid nodules occur wherever B cells need to mount responses against antigen: in the superficial cortex of every lymph node, in the splenic corpuscle of the splenic white pulp, in the tonsils (palatine, lingual, pharyngeal/adenoid), in Peyer's patches of the ileum, and scattered throughout the lamina propria of the gut and airway mucosae as part of MALT (mucosa-associated lymphoid tissue). The appendix is essentially a small intestine wrapped in confluent nodules. The thymus, by contrast, has no nodules at all.

Clinical anchor

Follicular lymphoma is a B-cell malignancy of germinal-centre origin in which the t(14;18) translocation places the anti-apoptotic BCL-2 gene under control of the immunoglobulin heavy-chain enhancer. Centrocytes that should have died in the selection step instead survive indefinitely; the resulting lymph node fills with monomorphic, back-to-back follicles that have lost their tingible-body macrophages.