The immune system relies on a network of specialised organs and tissues where immune cells are produced, mature, and carry out their defensive functions. These lymphoid organs are classified into primary and secondary based on their specific roles in lymphocyte biology. Primary lymphoid organs provide the environment where lymphocytes differentiate from haematopoietic stem cells and mature into immunocompetent (antigen-recognising) but antigen-naive cells. Secondary lymphoid organs provide specialised environments where mature, antigen-naive lymphocytes encounter antigens (presented by antigen-presenting cells like dendritic cells and macrophages), become activated, proliferate, and differentiate into effector cells that carry out immune responses, as well as memory cells that provide long-lasting immunity.

Bone marrow: located in the cancellous (spongy) bone of axial skeleton (sternum, ribs, vertebrae, pelvis) and in long bone epiphyses in adults. Contains haematopoietic stem cells (HSCs) that give rise to all blood cells, including lymphocytes. B lymphocytes undergo their entire development and maturation within the bone marrow itself (hence "B" for Bone marrow) — immature B cells undergo V(D)J recombination to generate diverse B cell receptors, then positive selection for functional BCR expression and negative selection to delete self-reactive B cells, before exiting as mature naive B cells. T lymphocyte precursors originate in the bone marrow but must migrate to the thymus for their maturation. Thymus: a bilobed organ in the anterior mediastinum above the pericardium; most active in childhood and early adulthood, with progressive fatty replacement (involution) after puberty. T lymphocyte precursors (thymocytes) migrate from bone marrow to the thymus cortex, where they undergo V(D)J recombination to generate diverse T cell receptors; positive selection in the cortex ensures T cells can recognise peptides presented on self-MHC molecules; negative selection in the medulla deletes strongly self-reactive T cells; survivors emerge as mature naive CD4+ or CD8+ T cells. Thymus is absolutely essential for T cell development — children born without a thymus (DiGeorge syndrome) completely lack T cells and have severe combined immunodeficiency.

Secondary lymphoid organs are strategically positioned at sites where foreign antigens are likely to enter or concentrate, ensuring that circulating antigen-naive lymphocytes have maximum opportunity to encounter the antigens they are specific for. Spleen: largest secondary lymphoid organ; filters blood and mounts immune responses to blood-borne antigens; white pulp contains periarteriolar lymphoid sheaths (PALS, T cell zones around central arterioles) and primary and secondary lymphoid follicles (B cell zones containing germinal centres during active antibody responses); marginal zone between white and red pulp contains specialised macrophages and B cells for rapid T-independent antibody responses to polysaccharide antigens. Lymph nodes: small bean-shaped organs (~1 cm) distributed throughout the lymphatic system; filter lymph and mount responses to antigens carried in lymph from peripheral tissues; have a cortex (B cell follicles), paracortex (T cell zones with high endothelial venules for lymphocyte recirculation), and medulla with plasma cells secreting antibodies into the efferent lymph. Tonsils: lymphoid tissue in the oropharynx sampling antigens entering via the respiratory and digestive tracts. Peyer's patches: gut-associated lymphoid tissue in the ileum sampling intestinal antigens.

A critical aspect of adaptive immunity is the recirculation of lymphocytes through secondary lymphoid organs, which enables antigen-specific lymphocytes (present in very low frequency in the body — perhaps 1 in 10^5 to 10^6 lymphocytes is specific for any given antigen) to continuously survey secondary lymphoid organs for the antigens they recognise, dramatically increasing the probability that a rare antigen-specific lymphocyte will encounter its specific antigen during the relatively brief window when that antigen is present in the body. Naive lymphocytes enter secondary lymphoid organs from the bloodstream through specialised high endothelial venules (HEVs) — unique post-capillary venules expressing tissue-specific adhesion molecules and chemokines that direct naive T and B cells to enter the lymph node or spleen. If a lymphocyte does not find its specific antigen within a secondary lymphoid organ, it exits via efferent lymphatics (or splenic sinusoids) back into the bloodstream and continues circulating. This continuous recirculation through all secondary lymphoid organs ensures that every naive lymphocyte has repeated opportunities to survey the entire lymphoid system for its antigen, while also concentrating antigen-presenting cells and antigen-specific lymphocytes together in secondary lymphoid organs where activation can occur efficiently.