The following points highlight the two main types of organs present in immune system of humans. The types are: 1. Primary Lymphoid Organs 2. Secondary Lymphoid Organs.
Type # 1. Primary Lymphoid Organs:
Primary lymphoid organs (PLO) are the major sites of lymphocyte development i.e. lymphopoiesis. Lymphocytes differentiate from lymphoid stem cells, proliferate and mature into functional cells called immuno-competent cells. In mammals, B-cell maturation occurs in the bone marrow and T-cell maturation occurs in the thymus.
Thymus:
i. Location:
Thymus is located in the thoracic cavity (in the mediastinum), just above the heart and beneath the breast bone (Fig. 3.2.1).
ii. Origin:
In mammals thymus develops from the endoderm of the third and fourth pharyngeal pouch.
iii. Structure:
The thymus is flat, bilobed, greyish lympho-epithelial organ. Each lobe is made of lobules separated from each other by strands of connective-tissue trabeculae and covered by a capsule. Each lobule consists of two compartments the outer compartment (cortex) is densely packed with immature T-cells (thymocytes) and the inner compartment (medulla) is sparsely populated with mature thymocytes (Fig. 3.3) which express CD44 (not found in the cortical thymocytes).
iv. Cell types of thymus:
There are basically four types of cells found in thymus— thymocytes, dendritic cells, epithelial cells and macrophages. Both the cortex and medulla of the thymus are crisscrossed by a three dimensional stromal-cell network.
v. Functions:
i. Out of four cell types, dendritic cells, epithelial cells and macrophages act in a combine manner, as a framework to assist in thymocyte maturation. Some thymic epithelial cells in the outer cortex, called nurse cells, have long membrane processes which surround as many as 50 thymocytes forming large multicellular complexes. Other cortical epithelial cells have long inter-connecting cytoplasmic processes that form a network.
ii. The thymocytes are differentiated and matured into different types of T-cells under hormonal influence. Lymphoid progenitor cells formed in the bone marrow migrate to the thymus under the influence of specialized thymic environment.
Maturation of T-cells:
There are four types of hormones named as α1-thymosin, β4-thymsin, thymopoeitin and thymulin (and thymic factor and. thymic humoral factor). The T-cell progenitors formed in the bone marrow during hematopoiesis, begin to migrate to the thymus at the 9th week of gestation in humans.
Thymosin is a protein with lymphocytopoietic capacity which is able to enhance maturation of pro-thymocytes to mature T-cells. Maturation of T-cells is also supported by interleukin-7(IL-7) which is produced from the thymic stromal cells. During the maturation of thymocytes within thymus, the antigenic diversity of the T-cell receptors, generated by various gene arrangement.
In this process class I and class II MHC (Major Histocompatibility Complex) level also help to recognize self MHC and foreign molecules by maturing thymocytes. Finally, cells with such self- recognition power are selected and rest are (95%-99%) being self destructed by different external and internal factors called programmed cell death (PCD).
i. Proliferation of mature T-cell:
After maturation is completed, the mature T- cells leave thymus via post capillary venules of cortico-medullary junctions. Again they will migrate into different target oriented secondary lymphoid tissues. Thymus is one of the most important primary lymphoid organ as because it is meant for generation of T- cells which have immense importance in cell mediated immune response.
ii. Effect:
Effect of Thymus is detected several times by several removal of thymus (thymectomy), in mice, at birth, creates immune defects in the branch of cell-mediated immunity. Even if a grafting of thymus is done to a new born mice that will show better results.
Bone marrow:
i. Location:
It is found in the cavities of most bones in the body including the skull, ribs, sternum, femur and spine. In birds, no bone marrow is found to be present, instead a lymphoid organ named Bursa identified by Fabricius called Bursa of Fabricius, is present and performs the same duty of bone marrow of mammals.
ii. Structure:
Bone marrow of different bones mainly consists of a sponge like reticular framework located between long trabeculae. The spaces in this framework are filled with fat cells, stromal fibroblasts and precursors of blood cells (Fig. 3.4).
iii. Function:
The bone marrow is the main site of generation of all types of circulating blood cells in adult and is the principal site of B-cell maturation and proliferation. During foetal development, the generation of all blood cells, called haematopoiesis, occurs initially in blood island of yolk sac and para-aortic mesenchyme and later in the liver and spleen.
Gradually, these functions are shifted to bone marrow. All blood cells originate from haematopoietic stem cell and become committed to differentiate along particular lineages (erythroid, megakaryocyte granulocytic, monocyte and lymphocytic).
Bone marrow is not only the source of all blood cells but also provides the microenvironment for the antigen independent differentiation of B-cell. Besides this, bone marrow serves as a secondary lymphoid organ where mature, virgin, antigen reactive lymphocytes (T & B cell) may respond to antigen, trapped by antigen presenting cells, such as macrophages. Thus, like spleen, bone marrow may provide an antigen processing environment.
Bursa of Fabricius:
i. Origin:
The Bursa is a lympho-epithelial organ, present as an intestinal pouch in birds only.
ii. Location:
It is located just above the cloaca of a chick and opens directly in the cloaca.
iii. Structure:
It is a hollow sac like structure (about 1 cm. in diameter) with a duct. It is lined with epithelial cells which cover outer cortical and inner medullary areas. The Bursa reaches its greatest size about one to two weeks after the chick’s hatching and then it gradually atrophies.
Inside it, folds of epithelium extend into the lumen, a number of follicles of lymphoid cells remain scattered through out the folds. Each follicle is divided into cortex and medulla. The cortex contains lymphocytes, plasma cells and macrophages.
At the boundary between these regions i.e. cortico-medullary junction, there is a basement membrane and capillary network. Inside of which epithelial cells are present. Each follicle is directly connected with the epithelium covering the surface of the fold (Fig. 3.5).
iv. Function:
The Bursa of birds serves as the hemopoietic inducing micro-environment for progenitor B-cells. It serves as a maturation and differentiation site for the lymphocytes of the antibody forming system. These cells are called B-lymphocytes or B-cells. Several hormones have been extracted from the Bursa. The most important of this is bursin, a tripeptide (lys-his-glycylamide). Bursin activates B-cells but not T-cells.
Type # 2. Secondary Lymphoid Organs:
Besides the primary lymphoid organs, there are some other lymphoid organs which are referred to as secondary lymphoid organs. Lymph nodes and spleen are the most important and highly organized secondary lymphoid organs.
Besides these, less organized lymphoid tissue collectively called mucosal-associated lymphoid tissue (MALT) which includes Peyer’s patches in the small intestine, the tonsils, the appendix, as well as numerous lymphoid follicles within the lamina propria of the intestines and in the mucous membranes lining the upper airways, bronchi and genital tract.
Importance of Secondary lymphoid organ:
In case of closed blood vascular system, blood remain always confined within the blood vessels. Lymph and lymphatic system bathe the tissue, tissue fluid and cells. As because lymphatic system represents an accessory route through which fluids or lymph can flow from interstitial spaces into the blood, which is comprised by tiny lymphatic vessels.
There are different organized lymphoid tissues which are located all along the lymphatic vessels, remain as diffuse collections of lymphocytes and the macrophages and some other are organized into structures called as the lymphoid follicles. These two remain as aggregates of various cells surrounded by a network of draining lymphatic capillaries. These are designated as secondary lymphoid tissues.
The secondary lymphoid organs are rich in macrophages and dendritic cells that trap and process antigens in T & B lymphocytes, which mediate the immune responses. The anatomical structure of these organs is designed to facilitate antigen trapping and its maximize opportunities for processed antigen are to be presented to antigen-sensitive cells.
Lymph nodes:
i. Location:
Lymph nodes are located at major junctions of the network of lymph flow through lymphatic channels (lymphatic vessels, Fig. 3.6).
ii. Structure:
The lymph nodes of man are round or bean shaped structures placed on lymphatic vessels so that they can filter out any foreign material carried in the lymph (Fig. 3.7 and 3.8). Lymph nodes consist of a fibrous reticular network filled with lymphocytes, macrophages and dendritic cells. Lymphatic sinuses penetrate the node.
A sub-capsular sinus is located immediately under the connective tissue capsule of the node; other sinuses pass through the node but are most prominent in a medulla. Afferent lymphatic vessels (those flowing into the node) enter the lymphatics node around its circumference, and efferent lymphatic vessels (those flowing out of the node) leave from depression (or hilus) on one side. The blood vessels supplying a lymph node also enter and leave via hilus.
The interior of a lymph node is divided into three concentric zones—an outer cortex, a para-cortex and a central medulla. Each of which provides a distinct micro-environment. The cells in the cortex are predominantly (B-cells) lymphocytes (arranged in nodules), macrophages and follicular dendritic cells arranged in primary follicles.
In lymph nodes, these follicles are stimulated by antigen, turned into secondary follicles to expand upto germinal centers where B-cells undergo somatic mutation.
Intense B-cell activation and differentiation into plasma and memory B-cells. It occur in the germinal centers of lymph nodes. Cells that increase their ability to respond to an antigen leave the germinal center to colonize other secondary lymphoid organs. Cells with reduced ability undergo apoptosis (programmed cell death) and are removed by macrophages.
The para-cortex sometime is referred to as thymus dependant area, in contrast to the cortex, which is thymus independent area. The para-cortex is largely constituted with T-lymphocytes and dendritic cells. The inter-digitating dendritic cells act as antigen presenting cells (APCS) and thus express class II MHC (Major Histocompatibility Complex) molecules.
The inner most layer of the lymph node is composed of lymphocytes, forming inter connecting strands in the medulla, called the medullary cord. Again these medullary cords surround the medullary sinuses which have plasma cells and some macrophages (Fig. 3.9).
Spleen:
i. Location:
Spleen, the secondary lymphoid organ is located high in the left abdominal cavity. The spleen is specially adapted for filtering blood and trapping blood-borne antigens and respond to systemic infections.
ii. Structure:
Spleen is one of the most important lymphoid organ remain surrounded by a capsule. From the capsule, a no. of projections called trabeculae remain extended to the interior to form a compartmentalized structure.
There are two types of compartments, named red pulp and white pulp.
These two pulps are separated by a diffused marginal zone:
i. Red pulp:
The red pulp of spleen consists of a network of sinusoids. Sinusoids are with huge macrophages and erythrocytes.
Function:
This splenic zone helps to destroy and remove old and defective red blood cells. Some of the macrophages within the red pulp contain engulfed red blood cells or iron pigments from degraded haemoglobin.
ii. White pulp:
This zone is with T-lymphocytes. It surrounds the periarteriolar lymphoid sheath (PALS).
Function:
The T-cell-rich-PALS mediate the initial activation of B and T cells. Here, dendritic cells capture antigen and present it with THelper (TH) cells. In terms these activated T-cells activate B cells. Activated B and TH cells together migrate to primary follicles present in the marginal zone. Primary follicles gradually develop characteristic secondary follicles after antigenic challenge and rapidly give rise to B-cells and plasma cells (Fig. 3.8).
Mucosal-associated lymphoid tissue:
Besides lymph nodes, spleen mucosal associated lymphoid tissue (MALT) is also considered as secondary lymphoid organ.
i. Location:
The digestive, respiratory and urogenital systems have a mucous membranes which are lined up by a vulnerable membrane with lymphoid tissues.
ii. Structure:
Loose cluster of lymphoid cells are present with little organizations in the lamina propria of intestinal villi to organised structures such as the tonsils, appendix and Peyer’s patches.
iii. Function:
MALTs are meant for the production of huge antibody-producing plasma cells which are very essential for the body defense (Fig. 3.9).
