The blood-forming tissues of the body (hematopoietic tissue) is a specialized form of connective tissue and is composed of two major divisions:
Lymphatic tissue is involved with lymphocyte production and immune responses. Lymphatic tissue has a major function in defending the body from disease and the spread of infection. Traces of foreign proteins (such as from invading microorganisms or cells) can elicit an immune response.
There is a constant recirculation of lymphocytes (especially T-lymphocytes) between the lymph and blood. The lymphocytes can leave the blood and enter the lymph system in specialized blood vessels (post-capillary venules) in lymph nodes. They eventually return to the blood together with the lymph via the thoracic duct. This recirculation involves lymphocytes that have acquired the ability to distinguish which molecules or cells belong to the body ("self") from foreign molecules or cells ("non-self"). These recirculating lymphocytes can be considered as being on protective patrol duties and are described as immunocompetent. When they encounter foreign molecules or cells they activate a series of immune responses to neutralize and destroy the invader.
TYPES OF LYMPHATIC TISSUE
There are three basic types of lymphatic (lymphoid) tissue:
Lymphatic nodules are found mainly in the loose connective tissue of many organs and in particular in the lamina propria of the digestive tract, upper respiratory tract and urinary passages. Nodules are temporary structures, which may appear and disappear in the same site. Nodules are spherical structures (0.2-1mm diameter) lacking a connective tissue capsule. They are mainly composed of dense aggregates of small B-lymphocytes. In many cases the cells at the center of the nodule are much larger, with more cytoplasm. This less-stained central area is known as the germinal center and develops according to the functional state of the nodule. Nodules with a germinal center are sometimes described as secondary nodules. The ring of small B-lymphocytes surrounding the germinal center is referred to as the corona or mantle zone. If these small peripheral lymphocytes are aggregated predominantly at one edge, they are referred to as a cap.
The germinal center is the site of proliferation
and differentiation of B-lymphocytes.
Cell types of the germinal center include :
Origin of lymphocytes
Bone marrow
The stem cells, from which lymphocytes originate, are found in the bone marrow. These stem cells are hard to distinguish morphologically.
CENTRAL LYMPHATIC ORGANS
The stem cells migrate to central lymphatic organs. These are sites of antigen-independent lymphocyte proliferation. Here the lymphocytes acquire their commitment for cell-mediated or humoral immune responses. The thymus is the site where T-lymphocytes develop. In birds the B-lymphocytes develop in a lymphatic structure in the cloacal region known as the Bursa of Fabricius. It is still not clear what is the equivalent central lymphatic organ for B-lymphocytes in humans, though there is increasing belief that this is possibly the bone marrow.
PERIPHERAL LYMPHATIC ORGANS
Peripheral lymphatic organs include the tonsils, lymph nodes and spleen. The T- and B-lymphocytes migrate to peripheral lymphatic organs, where they populate specific regions. T-lymphocytes, for example, are located in the paracortical zone of lymph nodes, in the periarterial sheath of the white pulp of the spleen or in loose lymphatic tissue such as the Peyer's Patches. The immunocompetent T-lymphocytes are also the main lymphocytes found in the blood and involved in recirculation. B-lymphocytes are found in the various lymphatic tissues of the body (lymphatic nodules, loose and dense lymphatic tissue) apart from the sites of the T-lymphocyte populations.
Effector cells
In the peripheral lymphatic organs both T- and B-lymphocytes respond to exposure to antigen and enlarge to form T-immunoblasts or B-immunoblasts (or lymphoblasts).
Some T-lymphocytes develop into T-memory cells. These cells only become effector cells if the body is exposed at some future date to the same antigen. This is the basis on which vaccines work. There are also suppressor T-cells, that operate as inhibitory cells and play a role in determining that the duration of the immune response is limited. The suppressor T-cells depress antibody production by depressing the conversion of B-lymphocytes into plasma cells (i.e. antagonistic effect to T-helper cells).
The cells circulating in the blood are mainly T-lymphocytes. T-lymphocytes and B-lymphocytes are morphologically identical, however they can be distinguished on the basis of different surface markers e.g. T-lymphocytes bind to sheep erythrocytes, whereas B-lymphocytes do not. Today there are large numbers of surface markers to distinguish the various lymphocytes.
Natural Killer cells
There are cytotoxic lymphocytes that are independent of the thymus. These are present even in animals lacking a thymus ("nude" mice). These cells are immunocompetent and respond to foreign cells (tumor cells, virus-infected cells) by developing into LAK cells (lymphokine activated killer cells).
Summary of components of immune system
Antigen-presenting cells hold or trap antigens on their surfaces so that these can be presented to B-lymphocytes (effector cells) resulting in antigen-antibody complexes. Antigen-presenting cells of the body include:
TONSILS
Tonsils are aggregates of lymphatic tissue, partly encapsulated, in the connective tissue associated with the oral and pharyngeal tract. They are best seen in the two palatine tonsils situated at the rear of the oral cavity and the start of the pharynx.
Stratified squamous epithelium with invaginations (crypts) covers the oral side of the tonsil. Lymphatic nodules and dense lymphatic tissue are present in the underlying lamina propria. The inner surface of the tonsils has a dense connective tissue capsule. Adjacent salivary glands are also commonly seen in histological preparations of tonsils.
LYMPH NODES
Lymph nodes are kidney-shaped structures situated along lymphatic vessels and serve as in-line mechanical filters of lymph. (They are sometimes incorrectly referred to as lymph glands, but this is a misnomer, as they are not glands and do not secrete).
The depression on the convex side of the node is called the hilum, which is the site of entry and exit of blood vessels and nerves. Lymph enters the node via a series of afferent lymphaticvessels on the convex surface and drains into a single efferent lymphatic vessel at the hilum. The lymph flow in the node is unidirectional, slow and passive. Valves in the lymphatic vessels prevent any backflow. A capsule of dense connective tissue surrounds the node. From this capsule extend radial trabeculae of connective tissue, to form incomplete compartments.
A loose reticular tissue extends throughout the node. This consists of reticulate cells and fibers, which form a network or scaffolding and which is well-demonstrated in preparations after silver impregnation techniques. This network provides an environment for the immunocompetent cells and antigen-presenting cells.
The lymph node is divided into two regions:
The sinuses of the node are irregular spaces formed of loose lymphatic tissue (reticular cells and fibers) containing various lymphocytes, antigen-presenting cells, macrophages. The sinuses act as mechanical filters in which lymph flow is extremely slow and are the sites where many cells are trapped. (This is the reason why biopsies of regional lymph nodes are examined to see if they contain cancer cells and the extent of the spread of the disease).
A paracortical zone, which lacks distinct morphological boundaries (situated between the cortex and the medulla,) is a region occupied by T-lymphocytes. This region has been shown to be thymus-dependent and if the thymus is removed experimentally, the paracortical zone disappears. Lymphocytes, mainly recirculating T-lymphocytes, leave the blood to repopulate the lymph nodes via post-capillary venules. These are blood vessels with unusual endothelium composed of tall or cuboidal endothelial cells. The T-lymphocytes can cross this endothelium to settle in the paracortical zone.
Antigens are trapped on the surface of antigen-presenting cells (dendritic follicular cells), where it is recognized and leads to B-cell activation to form B-immunoblasts and plasma cells, which produce specific antibodies. In cases of infection, lymph nodes become greatly enlarged.
THE SPLEEN
The spleen has a dense connective tissue capsule, with connective tissue trabeculae that divide the organ into incomplete compartments. The medial surface of the spleen has a hilum, which is the site for entry and exit of the blood vessels and nerves.
If a freshly cut spleen, small white spots (white pulp) consisting mainly of lymphatic nodules are visible embedded in soft, red, blood-rich tissue (red pulp).
White pulp
The white pulp consists of lymphatic tissue surrounding arteries and nodules also associated with arteries. The nodules can be distinguished because of the arteries (central arteries). Between the nodules and the red pulp is a marginal zone.
The lymphatic tissue immediately surrounding the central artery is known as the periarterial lymphatic sheath (PALS) and is composed of T-lymphocytes. The more peripheral part of the nodules is known as the peripheral white pulp (PWP) and consists of aggregates of B-lymphocytes. Dendcells in the marginal zone trap antigens and expose them to immunocompetent cells.
Red pulp
The red pulp is like a sponge composed of cords of cells (splenic cords) and splenic sinusoids (venous sinusoids).
The splenic cords (Billroth cords) are composed of :
Blood circulation
Tonsil Lymph node Lymph node Lymph node
Lymphatic nodule Afferent lymphatic Afferent lymphatic Subcapsular sinus
Subcapsular sinus Subcapsular sinus Subcapsular sinus. Lymph node medulla
Lymph node medulla Macrophages Spleen Spleen
Spleen Red pulp Central arteriole Central arteriole
Thymus Thymus Hassal bodies Hassal bodies
