Organs of the Immune System

Organs of the Immune System

Organs and tissues of immune responses are three types -  the primary and secondary lymphoid organs and tertiary lymphoid tissues.

Primary (or central) lymphoid organs - The thymus and bone marrow.  Here maturation of lymphocytes Takes place.

Secondary (or peripheral) lymphoid organs - The lymph nodes, spleen, and mucosal associated Lymphoid tissues (MALT).  These trap antigen and provide sites for mature lymphocytes to interact with that antigen.

Tertiary lymphoid tissues - cutaneous-associated lymphoid tissues.  they contain fewer lymphoid cells than secondary lymphoid organs, can bring in lymphoid cells during an inflammatory response.

Primary Lymphoid Organs

Immature lymphocytes generated through hematopoiesis mature and become committed to a particular antigenic specificity in the primary lymphoid organs. A lymphocyte become immunocompetent within a primary lymphoid organ.

T cells arise in the thymus, and in many mammals B cells originate in bone marrow. 

Thymus 

The thymus is the site of T-cell development and maturation.  The thymus reaches its maximal size at puberty and then atrophies.  Its size is 70g infants and 3 g in adults.

It is a flat, bilobed organ situated above the heart. Each lobe 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  (cortex) is densely packed with immature T cells (thymocytes).  The inner compartment (medulla) is sparsely populated with thymocytes.

Both the cortex and medulla of the thymus are crisscrossed by a stromal-cell network composed of epithelial cells, dendritic cells, and macrophages. These cells function in maturation of T cells. 

Nurse cells are thymic epithelial cells in the outer cortex and have long membrane extensions that surround as many as 50 thymocytes. Other cortical epithelial cells have long interconnecting cytoplasmic extensions and interact with numerous thymocytes.

Thymus

The function of the thymus is to allow maturation of T cells to protect the body from infection. As thymocytes develop, an enormous diversity of T-cell receptors is generated by a random process.  Some of these receptors on T cells are capable of recognizing antigen-MHC complexes and some are not.  The thymus induces the death of those T cells that cannot recognize antigen- MHC complexes and those that react with self-antigen–MHC. More than 95% of all thymocytes die by apoptosis in the thymus without ever reaching maturity.

Bone Marrow

Bone marrow is the site of B-cell origin and development in humans and mice. In birds, a lymphoid organ called the bursa of Fabricius is the primary site of B-cellmaturation. In cattle and sheep, B-cell origin and development occur in ileal Peyer’s patch (in the wall of the intestine)

Immature B cells proliferate and differentiate within the bone marrow.   Stromal cells within the bone marrow secrete various cytokines and interact directly with the B cells. A selection process within the bone marrow eliminates B cells with self-reactive antibody receptors.

Lymphatic System

The lymphatic system is a vascular network of tubules and ducts that collect, filter, and return lymph to blood circulation. Lymph is a clear fluid that comes from blood plasma. Lymph contains water, proteins, salts, lipids, white blood cells, etc.

 Lymphatic System

As blood circulates under pressure, its fluid component (plasma) seeps through the thin wall of the capillaries into the surrounding tissue.  This fluid is called interstitial fluid and a major portion of this returns to the blood through the capillary membranes. The remainder of this interstitial fluid flows  into a network of tiny lymphatic capillaries.  This fluid is now called lymph.  From tiny lymphatic capillaries it flows into a series of progressively larger collecting vessels called lymphatic vessels and reaches lymph node.   Lymph nodes are organized lymphoid tissues.  As lymph leaves the nodes, it is carried through larger efferent lymphatic vessels, which eventually drain into the circulatory system at the thoracic duct or right lymphatic duct. The largest lymphatic vessel is the thoracic duct.  It empties into the left subclavian vein near the heart.

The primary functions of the lymphatic system are

· to drain and return interstitial fluid to the blood

· to absorb and return lipids from the digestive system to the blood

· to filter fluid of pathogens, damaged cells, cellular debris, and cancerous cells.

The flow of lymph is achieved as the lymph vessels are squeezed by movements of the body’s muscles. There are a  series of one-way valves along the lymphatic vessels and they ensures that lymph flows in one direction.

When a foreign antigen gains entrance to the tissues, it is picked up by the lymphatic system.  The antigen is carried to lymph nodes.  Here the lymphocytes interact with the trapped antigen and undergo activation.  Lymph nodes act as filters for antigens.

Secondary Lymphoid Organs

Various types of organized lymphoid tissues are

located along the vessels of the lymphatic system.

A lymphoid follicle (a primary follicle) is a network of follicular dendritic cells and small resting B cells. When it encounters an antigen, a primary follicle becomes a larger secondary follicle.  A secondary lymphoid follicle consists of a large germinal center surrounded by a dense mantle of small lymphocytes. The centre contains proliferating B lymphocytes and surrounded by nondividing B cells, helper T cells, macrophages and follicular dendritic cells.

Lymph nodes and spleen are the secondary lymphoid organs.  They comprise of lymphoid follicles and additional distinct regions of Tcell and B-cell activity, and are surrounded by a fibrous capsule.

Mucosal-associated lymphoid tissue (MALT) are less-organized lymphoid tissue.  It is found in various body sites. MALT includes Peyer’s patches (in the small intestine), the tonsils, and 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.

Lymph nodes

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

Morphologically, a lymph node can be divided into three roughly concentric regions: the cortex, the  paracortex, and the medulla. 

                                                                       Lymph node

The cortex is the outermost layer.  It contains lymphocytes (mostly B cells), macro-phages, and follicular dendritic cells arranged in primary follicles. After antigenic challenge, the primary follicles enlarge into secondary follicles, each containing a germinal center.

Under the cortex is the paracortex.  This is populated largely by T lymphocytes and interdigitating dendritic cells. These interdigitating dendritic cells express high levels of class II MHC molecules,which are necessary for presenting antigen to T_H cells.

The innermost layer of a lymph node is the medulla.  It is more sparsely populated and contain plasma cells (actively secreting antibody molecules).

Afferent lymphatic vessels empty lymph into the lymph node. Lymph coming from the tissues percolates slowly inward through the cortex, paracortex, and medulla.  The phagocytic cells and dendritic cells trap any bacteria or particulate material (antigen-antibody complexes) carried by the lymph.  Tthe lymph leaving a node through efferent lymphatic vessel is enriched with antibodies newly secreted by plasma cells (in medulla) and also has a fiftyfold higher concentration of lymphocytes than the afferent lymph.

Antigenic stimulation in a node increase the concentration of lymphocytes there.  This is due to increase in the proliferation and also due to increased migration of lymphocytes from the blood to the node.  Thus the node swells visibly.

Lymph nodes are specialized for trapping antigen from local tissues.

Spleen

The spleen is a large, ovoid secondary lymphoid organ situated high in the left abdominal cavity. The spleen functions in filtering blood and trapping blood-borne antigens and respond to systemic infections.

The spleen is surrounded by a capsule that extends a number of projections (trabeculae) into the interior, thus it has a compartmentalized structure. The compartments are of two types, the red pulp and white pulp, which are separated by a diffuse marginal zone. 

                                                                            Spleen

The splenic red pulp consists of a network of sinusoids.  This area contain macrophages and numerous red blood cells and few lymphocytes.  It is the site where old and defective red blood cells are destroyed and removed.  

The splenic white pulp surrounds the branches of the splenic artery, forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes. Primary lymphoid follicles are attached to the PALS. These follicles are rich in B cells and some of them contain germinal centers. The marginal zone is populated by lymphocytes and macrophages.

Blood-borne antigens and lymphocytes enter the spleen through the splenic artery and reaches the marginal zone. In the marginal zone, antigen is trapped by interdigitating dendritic cells, which carry it to the PALS. Here interdigitating dendritic cells capture antigen and present it combined with class II MHC molecules to T_H cells.   Once activated, these T_H cells can then activate B cells.

Mucosal-Associated Lymphoid Tissue

The mucous membranes lining the digestive, respiratory, and urogenital systems have a combined surface area of about 400 m² and are the major sites of entry for most pathogens. These vulnerable membrane surfaces are defended by a group of organized lymphoid tissues known as mucosal-associated lymphoid tissue (MALT). MALT contain large population of antibody-producing plasma cells (number exceeds that of total plasma cells in the spleen, lymph nodes and bone marrow).

MALT is populated by lymphocytes such as T cells and B cells, as well as plasma cells and macrophages, each of which is well situated to encounter antigens passing through the mucosal epithelium. In the case of intestinal MALT, M cells are also present, which sample antigen from the lumen and deliver it to the lymphoid tissue.  

Microfold cells (or M cells) are found in the gut-associated lymphoid tissue (GALT) of the Peyer's patches and in the mucosa-associated lymphoid tissue (MALT) of other parts of the gastrointestinal tract.  They have the unique ability to take up antigen from the lumen of the small intestine via endocytosis, phagocytosis, or transcytosis. Antigens are then delivered to antigen presenting cells.

These tissues may vary from loose, barely organized clusters to well-organized structures.  Examples for loose, barely organized clusters are lymphoid cells in the lamina propria of intestinal villi.  Examples for well-organized structures are tonsils, appendix, Peyer’s patches, etc.  

The components of MALT are subdivided into the following:

GALT - gut-associated lymphoid tissue. Peyer's patches are a component of GALT.

BALT  - bronchus-associated lymphoid tissue

NALT - nasal-associated lymphoid tissue

LALT - larynx-associated lymphoid tissue

SALT - skin-associated lymphoid tissue

CALT - conjunctiva-associated lymphoid tissue

LDALT - lacrimal duct-associated

The tonsils are found in three locations: lingual at the base of the tongue; palatine at the sides of the back of the mouth; and pharyngeal (adenoids) in the roof of the nasopharynx.  Tonsils are nodular structures consisting of a meshwork of reticular cells interspersed with lymphocytes, macrophages, granulocytes, and mast cells. The tonsils defend against antigens entering through the nasal and oral epithelial routes.

Cutaneous-Associated Lymphoid Tissue

The epidermal (outer) layer of the skin is composed largely of specialized epithelial cells called keratinocytes. These cells secrete a number of cytokines that may function to induce a local inflammatory reaction. In addition, keratinocytes can express class II MHC molecules and function as antigen-presenting cells. Langerhans cells, a type of dendritic cell, are scattered among the epithelial-cell matrix of the epidermis.  These cells can internalize antigen by phagocytosis or endocytosis. The Langerhans cells then migrate from the epidermis to regional lymph nodes, where they differentiate into interdigitating dendritic cells. These cells function as potent activators of naive TH cells.

The epidermis also contains intraepidermal lymphocytes.