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What makes up the lymphatic system?
Its own vasculature (lymphatic vessels and lymphatic capillaries filled with lymph) plus lymphoid organs and tissues.
Lymphoid tissues vs lymphoid organs
Tissues (no capsule): lymphoid nodules (e.g. tonsils) and MALT. Organs (encapsulated): lymph nodes, spleen, and thymus.
What is MALT and where is it found?
Mucosa-associated lymphoid tissue, found in the digestive tract (especially the appendix), respiratory, urinary, and reproductive systems. It is the most common lymphoid structure, roughly half of the lymphatic system.
Functions of lymphatic vessels
Collect excess interstitial fluid from tissues and return it to blood; screen antigens via lymph nodes; provide a highway for lymphocytes to recirculate from tissues to blood and for WBCs to deliver antigens to lymph nodes.
What is lymph?
Interstitial fluid (and the solutes it carries) after it enters lymphatic vessels.
Lymphatic capillary structure
Blind-ended (dead-end) vessels intermingled with blood capillary beds. Endothelial cells overlap and seal; accumulating fluid stretches the tissue and pulls them open. WBCs can squeeze in at any time.
How do lymphatic vessels prevent backflow?
Valves (bicuspid valves in larger vessels), like veins. Middle and outer layers resemble veins.
Lymphatic vessel histology tips
Not flushed during fixation, so lumens look pink from fixed protein; capillaries are thin-walled with overlapping endothelium (irregular inner surface); larger vessels show valve flaps.
Where does the lymphatic system drain into the blood?
Right lymphatic duct drains 1/4 of the body into the right subclavian vein. Thoracic duct drains 3/4 of the body into the left subclavian vein.
What is lymphedema and why is infection risk higher?
Swelling of distal limbs from blockage or damage to lymphatic vessels that prevents fluid drainage. Infection risk rises because lymph (with antigens and immune cells) can't be properly screened and cleared. Obesity is a major risk factor.
Lymph node structure: afferent vs efferent vessels and hilum
Multiple afferent lymphatic vessels bring lymph in; a single efferent vessel carries it out. The hilum is the entrance/exit for arteries, veins, and the efferent vessel. About 500 lymph nodes in the body.
What is the function of a lymph node?
Acts like a sieve that filters lymph and inspects it for signs of infection; a screening zone for antigens and a muster point for activated cells.
Flow of lymph through a lymph node
Afferent vessels -> outer cortex (B cell follicles screen antigens) -> deep cortex/parafollicular zone (T cells await antigen presentation by dendritic cells or macrophages) -> medulla (plasma cells secrete antibodies) -> efferent vessel.
Where do B cells and T cells live in a lymph node?
B cells: follicles in the outer cortex. T cells: deep cortex (parafollicular zone).
Primary vs secondary lymphoid follicles
Primary: contain naive (unactivated) B cells. Secondary: contain activated B cells dividing in a germinal center as they prepare an immune response.
Germinal center histology
Lighter and larger activated lymphocytes undergoing clonal expansion (mitotic figures visible), inside secondary follicles; surrounded by the darker naive lymphocytes of the follicle periphery. Reticular cells are also present.
What are high endothelial venules (HEVs)?
Specialized venules lined by simple cuboidal endothelium that let circulating lymphocytes enter the node directly. They mark the border between outer and deep cortex.
Lymph node medulla histology
Central, patchy appearance: medullary cords (dense patches including plasma cells) and medullary sinuses (less dense, leading toward the efferent vessel).
Reticular fibers in lymph nodes
Revealed by silver stains; reticular connective tissue forms a net-like scaffold for cells to interact without impeding lymph flow.
What do macrophages do in lymph nodes?
They are found in multiple locations, consume debris and pathogens, and present large antigens.
Dendritic cells: function
Tissue-resident, phagocytic leukocytes that link innate and adaptive immunity as antigen-presenting cells: they phagocytose microbes/debris, break them down, and present antigen fragments to lymphocytes to teach them to recognize pathogens.
How do naive lymphocytes recirculate?
They enter nodes through HEVs, dwell briefly, then re-enter the blood via efferent lymph and the thoracic duct to visit other nodes.
Spleen: functions
Removes and recycles abnormal/old blood cells; stores iron from recycled hemoglobin; screens the bloodstream for infection and starts immune responses. It is like a giant lymph node for the blood.
Spleen: white pulp vs red pulp
White pulp: houses T and B cells (PALS around central arterioles; B cell follicles with germinal centers). Red pulp: reserve and recycling center for RBCs, with many macrophages and splenic sinuses.
What is the PALS?
Periarterial lymphoid sheath: the T cell zone of white pulp lining the central arterioles; B cells are in follicles next to it.
Spleen histology landmarks
Capsule, trabeculae (connective tissue extensions of the capsule), white pulp with germinal centers, and red pulp. Arteries follow the trabeculae, branch into white pulp, and end in capillary beds in red pulp.
Spleen circulation: open vs closed
Many red pulp capillaries are open-ended and spill RBCs into the stroma (open circulation); closed circulation capillaries connect to sinuses. Splenic sinuses are sinusoidal capillaries that let RBCs re-enter circulation; reticular fibers maintain their structure.
How does the spleen's immune function differ from lymph nodes?
The spleen screens antigens and APCs in blood (not lymph) as they pass T and B cells.
Thymus: function
Site where immature T lymphocytes (born in bone marrow) circulate to and fully mature.
Thymus: cortex vs medulla
Cortex: densely packed with immature T cells (thymocytes); newest arrivals are least mature. Medulla: fewer thymocytes, more mature cells, and Hassall's corpuscles.
What is thymic selection?
In the medulla, epithelial cells present self antigens to thymocytes; any thymocyte that recognizes self is destroyed. Only mature T cells that don't recognize self leave (fewer than 5%).
Hassall's corpuscles
Distinctive structures in the thymic medulla (function unknown).
Epithelial reticular cells of the thymus
Epithelial-derived network that serves as a scaffold (instead of reticular fibers), presents self antigens to thymocytes, and forms the blood-thymus barrier preventing blood solutes from entering.
Thymus histology
Lobules separated by capsule and trabeculae; each lobule has a dark densely cellular cortex and paler medulla.
What is thymic involution?
Age-related shrinkage of the thymus: lobules shrink, cortical/medullary organization is disrupted, and adipose tissue fills the space.
Lymphoid nodules: function and size
Areas of loose connective tissue where lymphocytes congregate, guarding body entrances open to the environment (respiratory, digestive, urinary, reproductive tracts). Most are about 1 mm; some are 2-3 cm; may contain germinal centers.
Tonsils
The most prominent lymphoid nodules, in the pharynx. They are large because they guard the shared entrance of the digestive and respiratory tracts, which is heavily exposed to microbes.
Lymphoid nodule and MALT histology
Nodules appear as follicles in the lamina propria beneath epithelial linings (tonsil, ileum, appendix). Dense purple cells outside the nodules are diffuse MALT: B cells, T cells, macrophages, dendritic cells, plasma cells, and mast cells (plus some fibroblasts).
Where do all leukocytes originate and mature?
All are born in bone marrow where cytokines drive differentiation. Most also mature there, but immature T cells must go to the thymus.
Which lymphoid organs are encapsulated and what is their capsule extension called?
Lymph nodes, spleen, and thymus; connective tissue trabeculae extend inward from the capsule (spleen and thymus especially).