ORGANS OF THE IMMUNE SYSTEM
G. Mathew Srirangam
The immune system consists of many structurally and functionally diverse organs and tissues that are widely dispersed throughout the body. These organs can be classified based on functional differences into two main groups –
1. The primary lymphoid organs or Central lymphoid organs
2. The secondary lymphoid organs or Peripheral lymphoid organs.
The primary lymphoid organs provide appropriate microenvironments in which the precursor lymphocytes proliferate, develop and acquire immunological capability. And the secondary lymphoid organs trap antigen form defined tissues or vascular spaces and provide sites where mature lymphocytes can interact effectively with that antigen. The thymus and bone marrow constitute the primary lymphoid organs. Spleen, Lymph nodes and various mucosal-associated tissues (MALT) compose the secondary lymphoid organs.
Thymus develops from the epithelium of the third and fourth pharyngeal pouches at about the sixth week of gestation and by the eight week, grows into a compact epithelial structure. Mesenchymal stem cells or precursors of lymphocytes from the yolk sac, foetal liver and bone marrow reach the thymus and differentiate into the thymic lymphoid cells (thymocytes). The thymus acquires its characteristic lymphoid appearance by the third month of gestation. It is thus the first organ to become predominantly lymphoid. In human beings, the thymus reaches its maximal relative size just prior to birth. It continues to grow till about the 12th year. After puberty, it undergoes spontaneous progressive involution, indicating that it functions best in early life.
The thymus is a flat, bilobed organ located behind the upper part of the sternum above the heart. Each lobe of thymus is surrounded by a capsule and is divided into lobules, which are separated from each other by strands of connective tissue called trabeculae. Each lobule is organized into two compartments; the outer compartment or cortex, which is densely packed with immature T cells, called thymocytes. The inner compartment or medulla is sparsely populated with thymocytes but have mature lymphocytes between are present Hassall’s corpuscles which are whorl-like aggregations of epithelial cells. Both the cortex and medulla of the thymus are criss-crossed by a three-dimensional stroma-cell network composed of epithelial cells, interdigitating dendric cells and macrophages. Some epithelial cells in the outer cortex, called nurse cells, have long membrane processes that surround as many as 50 thymocytes, forming large multicellular complexes.
The primary function of thymus is the production of thymic lymphocytes or T lymphocytes or Thymus dependent (T) lymphocytes. It is the major site for lymphocyte proliferation. The thymus confers immunological competence on the lymphocytes during their stay in the organ, so that they are capable of mounting cell-mediated immune response against appropriate antigens. Finally the T lymphocytes are selectively seeded into certain sites in the peripheral lymphatic tissues, being found in the white pulp of the spleen, around the central arterioles and in the paracortical areas of lymphoid nodes. A congenital birth defect in humans called DiGeorge’s syndrome and in certain mice (nude mice) involves the failure of the thymus to develop T-lymphocytes and absence of cell-mediated immunity.
In birds a lymphoid organ called the bursa of Fabricus is the primary site of B-cell maturation. There is no bursa in mammals and no single counterpart to it as a primary lymphoid organ. Instead, regions of the bone marrow serve as the ‘bursal equivalent’ where B cell maturation occurs. Immature B cells proliferate and differentiate within the microenvironment of the bone marrow. Bone marrow is composed of hematopoietic cells of various lineage and maturity packed between fat cells, thin bands of bony tissue (trabeculae), collagen fibers, fibroblasts and dendritic cells. All the hematopoietic cells are derived from multipotential stem cells which give rise not only to all of the lymphoid cells found in the lymphoid tissue, but also to all of the cells found in the blood. The bone marrow gives rise to all of the lymphoid cells that migrate to the thymus for T-cell maturation as well as to the major population of conventional B cells. B cells mature in the bone marrow and undergo selection for non-self before making their way to the peripheral lymphoid tissues. Stromal cells within the bone marrow interacts directly with the B cells and secretes various cytokines that are required before the B-cell developmental process.
Spleen is a large, ovoid, secondary lymphoid organ situated high in the left abdominal cavity. Unlike lymph nodes, which are specialized to trap localized antigen from regional tissue spaces, the spleen is adapted to filtering blood and trapping blood-borne antigens, and thus can respond to systemic infections.
The spleen is surrounded by a capsule that sends a number of projections (trabeculae) into the interior to form a compartmentalized structure. The compartments are of two types, the red pulp and the white pulp, which are separated by a diffuse marginal zone. The splenic red pulp consists of a network of sinusoids populated with macrophages and numerous red blood cells (erythrocytes). It is the site where old and defective red blood cells are destroyed and removed. Many of the macrophages within the red pulp contain engulfed red blood cells or iron pigments from degraded hemoglobin. The splenic white pulp surrounds the arteries, forming a periarteriolar lymphoid sheath (PALS) populated mainly by T-lymphocytes. The marginal zone, located peripheral to the PALS, is rich in B cells organized into primary lymphoid follicles.
The main immunological function of the spleen is to filter the blood and trap blood borne microorganisms and producing an immune response to them.