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Lymphoid Organs: Lymph Nodes, Spleen, Thymus & MALT

Name: Lymphoid Organs: Lymph Nodes, Spleen, Thymus & MALT
Creator: Veli Bakalov, MD

Where lymphocytes are made, where they meet antigen, and what breaks when an organ is missing

Immunology·Immune Cells & Organs·7 min read·9 high-yield points·Reviewed by Veli Bakalov, MD @HemeOncBuddy

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Primary lymphoid organs (bone marrow, thymus) generate and educate lymphocytes; secondary organs (lymph nodes, spleen, MALT) are where naive lymphocytes meet antigen.
Lymph node follicles hold B cells (germinal centers when activated), the paracortex holds T cells and high endothelial venules, and the medulla holds plasma-cell cords and macrophage-lined sinuses.
The paracortex is underdeveloped in 22q11 deletion (DiGeorge) and expands in viral infections such as EBV mononucleosis.
Testes and ovaries drain to para-aortic nodes, while the scrotum and the anal canal below the pectinate line drain to superficial inguinal nodes.
Splenic red pulp (cords of Billroth and sinusoids) culls aged or IgG-coated RBCs; white pulp is the T-cell PALS plus B follicles; the marginal zone mounts T-independent responses to polysaccharide capsules.
Asplenia or sickle cell autosplenectomy predisposes to encapsulated organisms (S. pneumoniae, Hib, N. meningitidis, Salmonella, Klebsiella) and shows Howell-Jolly bodies, target cells and thrombocytosis.
Vaccinate against pneumococcus, Hib and meningococcus at least 2 weeks before elective splenectomy.
Thymus: third-pouch epithelium; cortex = immature thymocytes and positive selection, medulla = negative selection and Hassall corpuscles; absent thymic shadow in SCID and 22q11 deletion; thymoma causes myasthenia gravis and pure red cell aplasia.
M cells over ileal Peyer patches sample luminal antigens (a portal for Salmonella, Shigella, Yersinia), and Peyer patch B cells become plasma cells that make secretory IgA.

Organization of the lymphoid system

Primary lymphoid organs. Lymphocytes are generated and educated in the primary (central) organs. All lymphocytes arise from hematopoietic stem cells in the bone marrow, where B cells also complete their maturation; T-cell precursors travel to the thymus to mature. Cells leave these organs as naive lymphocytes that have not yet met their antigen.

Secondary lymphoid organs. Lymph nodes, the spleen and mucosa-associated lymphoid tissue (MALT: tonsils and adenoids, Peyer patches, appendix, bronchial lymphoid tissue) are where naive lymphocytes meet antigen presented by dendritic cells and become activated. Lymph nodes sample tissue fluid, the spleen samples blood, and MALT samples mucosal surfaces.

Recirculation. Naive lymphocytes continuously move from blood into secondary organs and back out through the lymph. They enter lymph nodes across high endothelial venules (HEVs), guided by L-selectin and the chemokine receptor CCR7, and exit through efferent lymphatics following a sphingosine-1-phosphate (S1P) gradient. Fingolimod, used in multiple sclerosis, blocks this S1P-guided exit and traps lymphocytes in the nodes.

Lymph nodes

Architecture. Afferent lymphatics pierce the capsule and empty into the subcapsular sinus. Lymph then filters through the cortical (trabecular) sinuses and the medullary sinuses and leaves by the efferent lymphatic at the hilum, where the artery enters and the vein exits.

Afferent lymphaticsEnter through the capsule, carrying antigen and dendritic cells from tissues
Subcapsular sinusFirst contact with cortical macrophages
Cortical and medullary sinusesMacrophages filter the lymph
Efferent lymphatic at the hilumCarries lymphocytes and antibody onward

The path of lymph through a node

Lymph node compartments

Zone	Main cells	Clinical correlation
Cortical follicles	B cells; germinal centers with follicular dendritic cells and tingible-body macrophages	Follicular hyperplasia (rheumatoid arthritis, toxoplasmosis, early HIV); follicular lymphoma
Paracortex	T cells, dendritic cells, high endothelial venules	Underdeveloped in 22q11 deletion; paracortical hyperplasia in viral infection (EBV)
Medullary cords	Plasma cells, lymphocytes	Antibody released into efferent lymph
Medullary sinuses	Macrophages, reticular cells	Sinus histiocytosis in nodes draining a cancer

Follicles. Primary follicles are dense collections of resting naive B cells. After antigen exposure they become secondary follicles with pale germinal centers, where B cells proliferate, undergo somatic hypermutation and class switching, and are selected on antigen held as immune complexes by follicular dendritic cells. Tingible-body macrophages clear the many B cells that die in the process.

Paracortex. This T-cell zone between the follicles and the medulla is where dendritic cells arriving from tissues present antigen to naive T cells. It is poorly developed when the thymus is absent (22q11 deletion) and expands in viral infections such as infectious mononucleosis.

Medulla. Medullary cords hold plasma cells that release antibody into the outgoing lymph, and macrophage-lined medullary sinuses perform a final filtering step.

Drainage patterns

Knowing where a region drains lets you predict which nodes enlarge first with an infection or tumor. The gonads are the classic trap: they drain with their vessels to para-aortic nodes, not to the groin.

High-yield lymphatic drainage

Region	First nodes
Testis, ovary	Para-aortic (lumbar)
Scrotum, vulva, most of the lower limb	Superficial inguinal
Anal canal below the pectinate line	Superficial inguinal
Lower rectum and anal canal above the pectinate line	Internal iliac
Posterolateral calf, lateral foot	Popliteal
Upper limb, lateral breast	Axillary
Medial breast	Parasternal (internal thoracic)
Stomach	Celiac

The right lymphatic duct drains the right head, neck, arm and chest; the thoracic duct drains everything else into the left subclavian–internal jugular junction.

An enlarged left supraclavicular (Virchow) node, fed by the thoracic duct, can be the first sign of an abdominal cancer such as gastric carcinoma.

Spleen

Red pulp. Most of the spleen is red pulp, a blood filter made of splenic cords (of Billroth), a macrophage-rich reticular meshwork, and venous sinusoids. To re-enter the circulation, red cells must squeeze through narrow slits between the elongated endothelial cells of the sinusoids. Aged, rigid or abnormal cells (spherocytes, sickle cells) and IgG-coated cells (warm autoimmune hemolytic anemia) are trapped and eaten by macrophages (culling), while inclusions such as nuclear remnants are removed from otherwise healthy cells (pitting). The spleen also holds about one third of the body's platelets.

White pulp. Central arterioles are sleeved by the periarteriolar lymphoid sheath (PALS) of T cells, with adjacent B-cell follicles that develop germinal centers when activated.

Marginal zone. At the junction of white and red pulp, marginal zone macrophages and B cells capture blood-borne antigens and produce rapid, T-independent IgM against bacterial polysaccharide capsules, supporting opsonization and clearance of encapsulated organisms. Because the marginal zone is immature before about age 2, young children respond poorly to plain polysaccharide vaccines; conjugating the polysaccharide to a protein recruits T-cell help and solves the problem.

Asplenia and hyposplenism

Causes. Surgical splenectomy (trauma, immune thrombocytopenia, hereditary spherocytosis), congenital asplenia, and functional asplenia. In sickle cell disease, repeated splenic infarction produces functional asplenia in early childhood and eventually a small fibrotic remnant (autosplenectomy).

Infections. Losing both the filter and marginal-zone antibody exposes patients to encapsulated bacteria: Streptococcus pneumoniae (the most common cause), Haemophilus influenzae type b, Neisseria meningitidis, Salmonella and Klebsiella. Overwhelming post-splenectomy infection can progress from fever to septic shock within hours. Capnocytophaga after dog bites, babesiosis and malaria are also more severe.

Blood findings. Without culling and pitting, the smear shows Howell-Jolly bodies (nuclear remnants), target cells, Pappenheimer and Heinz bodies and nucleated red cells. Loss of the splenic platelet pool causes thrombocytosis, and lymphocytosis is common.

~1/3of the body's platelets normally pool in the spleen

≥2 weeksbefore elective splenectomy to give vaccines

Prevention. Vaccinate against pneumococcus, Hib and meningococcus (plus yearly influenza) at least 2 weeks before elective splenectomy. Children with sickle cell disease receive daily penicillin prophylaxis in early childhood along with these vaccines, and every asplenic patient should seek care urgently for any fever.

Fever in an asplenic patient is an emergency: give empiric antibiotics immediately rather than waiting for culture results.

Thymus

Development and anatomy. The thymus lies in the anterior superior mediastinum. Its epithelial reticular framework derives from third pharyngeal pouch endoderm, the same pouch that gives rise to the inferior parathyroids, and it is colonized by bone marrow-derived T-cell precursors. It is largest relative to body size in infancy, producing the sail-shaped thymic shadow on infant chest films, and involutes into fat after puberty.

Thymic cortex vs medulla

Feature	Cortex	Medulla
Appearance	Dark, densely packed	Pale, less cellular
Thymocytes	Immature CD4+CD8+ (double positive)	Mature CD4+ or CD8+ (single positive)
Selection	Positive selection on cortical epithelial cells (MHC restriction)	Negative selection against self-antigens (AIRE)
Landmark	Numerous dividing thymocytes	Hassall corpuscles (keratinized epithelial whorls)

Absent thymic shadow. An infant chest film without a thymic shadow suggests severe combined immunodeficiency (no functional T cells; recurrent infections, thrush, chronic diarrhea, failure to thrive) or 22q11.2 deletion (DiGeorge), in which third and fourth pouch failure causes thymic aplasia, hypocalcemia from absent parathyroids and conotruncal heart defects.

Thymoma. An epithelial tumor and a classic anterior mediastinal mass. Its paraneoplastic associations are myasthenia gravis (anti-acetylcholine receptor antibodies), pure red cell aplasia and hypogammaglobulinemia. Among patients with myasthenia gravis, thymic hyperplasia is more common than thymoma, and thymectomy can improve the disease.

Mucosa-associated lymphoid tissue

M cells. Microfold (M) cells in the epithelium overlying Peyer patches of the ileum and other MALT transcytose luminal antigens to dendritic cells and lymphocytes beneath them. Salmonella, Shigella, Yersinia and poliovirus exploit this route to invade.

Secretory IgA. B cells primed in Peyer patches switch to IgA under TGF-β and T-cell help, then home back to the lamina propria as plasma cells. They secrete dimeric IgA joined by a J chain; the polymeric immunoglobulin receptor carries it across the epithelium and is cleaved to leave secretory component attached, which protects IgA in the lumen. IgA is the antibody the body produces in the greatest amount, even though IgG dominates in serum.

Clinical links. Hypertrophied Peyer patches after a viral illness are the usual lead point of ileocolic intussusception in toddlers. Chronic antigen stimulation of MALT can give rise to marginal zone (MALT) lymphoma, as in Helicobacter pylori gastritis, which may regress after eradication of the infection.