Thursday, July 26, 2007

SECONDARY LYMPHOID ORGANS
- Mathew Srirangam
Lymphatic System
As blood circulates under pressure, the fluid component of the blood (plasma) seeps through the thin wall of the capillaries into the surrounding tissues. This fluid is called the interstitial fluid or extra cellular fluid. Much of this fluid returns to the blood through the capillary membranes. The reminder of the interstitial fluid now called lymph flows from the connective tissue spaces into a network of thin open lymphatic capillaries and then into a series of progressively larges collecting vessels called lymphatic vessels. The largest lymphatic vessel called the thoracic duct opens into the left subclavian vein near the heart. In this way lymphatic system functions to capture fluid lost from the blood and returns it to the blood, thus ensuring the fluid steady state of the blood.

As the lymph is draining the connective tissues of the body, when a foreign antigen gains entrance into the tissues, it is picked up by the lymphatic system, and carried to various organized lymphatic tissues, which trap the antigen. Various types of organized lymphoid tissues are located along the vessels of the lymphatic system.

Some lymphoid tissues in the lung and lamina propria of the intestinal wall consist of diffuse collections of lymphocytes and macrophages. Other lymphoid tissue is organized into structures called lymphoid follicles. In the absence of antigen stimulus, a lymphoid follicle called primary follicle, comprises a network of follicular dendritic cells and small resting B-cells. Following an antigenic challenge, a primary follicle becomes a large secondary follicle – a ring of concentrically packed B lymphocytes surrounding a center called the germinal center in which proliferating B lymphocytes, memory cells and plasma cells are interspersed with macrophages and follicular dendritic cells.

Dendritic cells in lymphoid organs are two types.
In T-cell areas they are
called interdigitating dendritic cells
and in B-cell areas they are
called follicular dendritic cells
.

The germinal center is a site of intense B-cell activation. Here the B-cells that interact with antigen displayed on the membrane of follicular dendritic cells are induced to proliferate and differentiate into plasma and memory cells. In the absence of antigen activation, the B-cells appear to undergo programmed cell death with in the germinal center.

In order to maintain steady state levels of cells, the cells undergo programmed
cell death. These cells exhibit morphological changes collectively called
apoptosis. Apoptosis includes, decrease in cell volume, modification of
the cytoskeleton resulting in pronounced membrane blebbing (pinching off small
pieces).

Lymph Nodes:
Lymph nodes are encapsulated bean shaped structures containing a reticular network packed with lymphocytes, macrophages and dendritic cells. Clustered at junctions of the lymphatic vessels, lymph nodes are the first organized lymphoid structure to encounter the antigens that enter the tissue spaces. As lymph percolates through a node, the cellular network of phagocytic cells and dendritic cells will trap any particulate antigen that is brought in with the lymph.

Morphologically, a lymph node can be divided into three roughly concentric regions – the cortex, the paracortex and the medulla. The outermost layer, the cortex consists of lymphocytes (mostly B cells) macrophages, and follicular dendritic cells arranged in primary follicle. With antigenic challenge, the primary follicles enlarge into secondary follicles, each containing la germinal center. Intense B-cells activation and differentiation into plasma and memory cells occur in the germinal centers. Beneath the cortex is the paracortex, which is populated largely with T-lymphocytes and also contains interdigitating dendritic cells. These dendritic cells express high levels of Class II MHC molecules, which are necessary for antigen presentation to TH cells. The innermost layer of lymph node is the medulla, which is sparsely populated with lymphocytes, but many of these are plasma cells.

Afferent lymphatic vessels pierce the capsule of lymph node at numerous sites and empty lymph into the sub capsular sinus. Lymph coming from the tissues percolates slowly inward through the cortex, the paracortex and medulla; allowing phagocytic cells and dendritic cells to trap any bacteria or particulate material, (like antigen-antibody complexes) carried by the lymph.

The trapped antigen is processed and presented together with Class I MHC molecules by interdigitating dendritic cells in the paracortex resulting in TH cell activation. Followed by the activation of B cells. TH and B cells bring about their immunological responses respectively.

Spleen

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.

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