Lymphoid Organs and Their Functions

"The organs of the immune system may be divided into the primary, or generative, lymphoid organs (bone marrow and thymus), where lymphocytes mature, and the secondary, or peripheral, lymphoid organs (lymph nodes, spleen, and the mucosal and cutaneous immune systems), where lymphocytes are activated by antigens."

• Robbins & Kumar Basic Pathology

1. Primary (Generative) Lymphoid Organs

A. Bone Marrow

• The source of all blood cells, including lymphocytes (haematopoiesis)
• Site of B lymphocyte maturation - B cells complete their development here and become mature naive B cells
• Releases mature B and T cell precursors into the circulation
• T cell precursors leave the bone marrow early and migrate to the thymus to finish maturing
• Contains ~50 x 10⁹ lymphocytes in a healthy adult

B. Thymus

• Located in the upper anterior mediastinum (chest)
• The exclusive site of T lymphocyte maturation
• T cell precursors from bone marrow migrate here and undergo:
  • Positive selection - cells that can recognize self-MHC molecules survive
  • Negative selection - self-reactive cells are eliminated (clonal deletion) to prevent autoimmunity
• The thymus environment transforms precursors into functional, self-tolerant T cells
• Mature T cells are then released into the circulation to populate secondary lymphoid organs
• The thymus contains 100% T lymphocytes and 0% B lymphocytes (unlike all other lymphoid organs)

2. Secondary (Peripheral) Lymphoid Organs

"The secondary lymphoid organs are organized to concentrate antigens, APCs, and lymphocytes in a way that optimizes interactions among these cells and the development of adaptive immune responses."

• Robbins & Kumar Basic Pathology

A. Lymph Nodes

• Cortex - contains B cell follicles (primary follicles = naive B cells; secondary follicles = germinal centers where B cells are actively responding to antigen)
• Paracortex (T cell zone) - rich in T lymphocytes and dendritic cells
• Medulla - contains plasma cells and macrophages

1. Antigen surveillance - as lymph drains from tissues, APCs (especially dendritic cells) carry antigens to the node via afferent lymphatics
2. Immune activation - naive T and B cells circulating through the node encounter antigen-bearing dendritic cells and become activated
3. Effector cell production - activated lymphocytes proliferate and differentiate; effector T cells leave via the efferent lymphatic vessel and return to bloodstream to fight infection
4. Antibody production - activated B cells form germinal centers in follicles and differentiate into antibody-secreting plasma cells

Fig: Morphology of a lymph node. (A) Histological cross-section. (B) Schematic showing T cell zone (paracortex) and B cell zone (follicles). (C) Immunostaining showing B cells (green) and T cells (red). - Robbins & Kumar Basic Pathology

B. Spleen

• Red pulp - a network of vascular sinusoids filled with blood; site of red blood cell destruction and blood filtration
• White pulp - lymphoid tissue organized around central arterioles:
  • Periarteriolar lymphoid sheath (PALS) - T cell zone surrounding the central arteriole
  • Follicles - B cell zones; secondary follicles contain germinal centers
  • Marginal zone - transition zone between red and white pulp; important for trapping blood-borne antigens

1. Immune surveillance of blood - blood entering the spleen flows through sinusoids where DCs and macrophages trap bloodborne antigens and microbes
2. Initiation of immune responses - antigen-bearing DCs present antigens to T and B cells in the white pulp
3. Blood filtration - removes old, damaged, or opsonized red blood cells (red pulp macrophages phagocytose them)
4. Blood reservoir - the red pulp stores concentrated red blood cells that can be mobilized by the sympathetic nervous system (up to 50 mL released during stress)
5. Defense against encapsulated bacteria - asplenic patients are highly susceptible to infections with organisms like Streptococcus pneumoniae

Fig: Functional structure of the spleen - Guyton & Hall Textbook of Medical Physiology

C. Mucosa-Associated Lymphoid Tissue (MALT)

• Gut-associated lymphoid tissue (GALT) includes tonsils, adenoids, appendix, and Peyer's patches
• Peyer's patches (in the small intestine) are the most organized MALT structures; they collect antigens from the gut via specialized M cells (microfold cells) in the epithelium
• The mucosal immune system is estimated to contain as many lymphocytes as all the rest of the body combined
• Lymphocytes generated in mucosal lymphoid tissue preferentially home back to mucosal surfaces ("homing")

3. Distribution of Lymphocytes Across Organs (Healthy Adult)

4. Key Differences: Primary vs. Secondary Lymphoid Organs

Summary

• Robbins & Kumar Basic Pathology, p. 161
• Janeway's Immunobiology 10e, p. 40-46
• Cellular and Molecular Immunology, p. 128-129
• Guyton and Hall Textbook of Medical Physiology