Primary Lymphoid Organs are the locations were the Haematopoietic Stem Cells mature into fully functional immune cells. Humans have to two primary lymphoid organs, the Bone Marrow and the Thymus. These two organs will be discussed in detail below.

Bone Marrow

• The bone marrow is the site of differentiation of the HSCs into immune cells as well as the site of the maturation for B lymphocytes.

• The bone marrow consists of several cell types.

  • Osteoblasts - Generate bone and control the differentiation of HSCs

  • Endothelial cells - Line the blood vessels and regulate HSC differentiation

  • Reticular cells - The long processes of this cell connect bone and blood vessels

  • Sympathetic neurons - Control the release of HSCs from the bone marrow

• As we established in the previous infodumps, all the immune cells arise from the HSC. However the proliferation and differentiation of the HSCs into fully functional leucocytes is a result of the microenvironments.

  • These microenvironments, known as Stem Cell Niches, consist of a supportive network of Stromal Cells.

  • The stromal cells regulate the survival, proliferation, differentiation and trafficking of the HSCs by expressing soluble as well as membrane-bound proteins.

  • The bone marrow has two stem cell niches.

    • Endosteal niche - The region surrounding the bone. It is in contact with osteoblasts. Occupied by quiescent HSCs.

    • Vascular niche - The region surrounding the blood vessels. It is in contact with endothelial cells. Occupied by HSCs that are differentiating or migrate into the circulatory system.

  • The more differentiated a cell is, the farther it migrates from the supportive osteoblasts to the central region of the bone enriched with blood vessels.

• Although bones contain bone marrow, the long bones (femur and humerus), the hip bones (ileum) and the sternum are the most active sites for haematopoiesis.

Thymus

• Thymus is the site of maturation for T lymphocytes.

• Originally, the organ was thought to be a graveyard for immune cells.

• In the 1960s, J.F.A.P. Miller proved this hypothesis wrong by establishing the important function of the thymus in the maturation of the T cells.

• T-cell precursors migrate to the thymus through blood from the bone marrow.

• The immature T cells are known as Thymocytes.

• The thymocytes generate antigen specific receptors known as T cell receptors (TCR) in the process of maturation.

• These cells are then selected on the basis of reactivity to self MHC-peptide complexes expressed by stromal cells in the thymus.

• Almost 95% of the cells do not survive this selection process.

• As the cells undergo the maturation process, they traverse through the various microenvironments of the thymus.

  • The T cell precursors enters the thymus through the blood cell at the corticomedullary junction between the thymic cortex, the outer portion of the organ, and the thymic medulla, the inner portion of the organ. The cells at this stage express neither CD4 nor CD8 receptors (Double Negative - DN cells).

  • The DN cells migrate to the subcapsular cortex where they start expressing both CD4 and CD8 receptors (Double Positive - DP cells).

  • The cortical thymic epithelial cells, a type of thymic stromal cells, test the T cells ability to bind to MHC-peptide complexes.

  • After the selection process, the surviving cells travel to the thymic medulla, where the medullary thymic epithelial cells support the final stages of maturation.

  • These stromal cells also express proteins of other organs to eliminate any T cells that may damage the body.

  • Mature thymocytes that express either CD4 or CD8 (Single Positive - SP cells) leave the thymus through the blood vessels of the corticomedullary junction.