Introduction/Definitions:
Lymphatic system: is a compartmentalized network of vessels, cells and specialized accessroy organs. It starts in the farthest reaches of the tissues as tiny capilaries that transports a special fluid (lymph) through an increasingly larger tributary system of vessels and filters (lymph- nodes) and leads to major vessels that drain back into the regular circulatory system. Because one of the main functions of the lymphatic system is returning lymph to the circulation, the flow of lymph is one direction only moving from the extremities toward the heart. This is unlike with the bloodstream. Eventually lymph will return to the bloodstream through the thoractic duct or the right lymphatic duct to the subclavian vein near the heart. While blood is transported through the body by means of the heart, lymph is moved only through the contraction of the skeletal muscles through which the lymphatic ducts exist. This dependence on muscle movement helps explain the swelling of the hands and feets that sometimes occur during the night when muscles are inactive.
Lymphatic fluid: Lymph is a plasmalike liquid carried by the lymphatic circulation. It is formed when parts of the blood (not the red blood cells) move out of the blood vessels into the extracellular spaces and diffuse into the lymphatic capillaries. It transports numerous white blood cells, miscellaneous materials such as fats, cllular debris and infectious agents that have gained access to the tissue spaces.
Primary Lymphoid organs:
The primary lymphoid organs include the bone marrow and thymus.
Red Bone Marrow: is where B maturation occurs. The red bone marrow is typically found in flat bones and the ends of long bones and is the site of blood cell production. All blood cells originate int eh bone marrow, including B and T lymphcyte precursors. Afer B lymphocytes being to express markers that identify them as B cells, they complete their maturaiton process while still in the bone marrow and then migrate to secondary lymphatic organs such as the spleen or lymph nodes where they wait to encounter foreign antigen.
Thymus is where T cell maturation occurs. T cell progenitors formed during hematopoiesis enter the thymus gland and mature there to become antigen committed, immunocompetent. In the course of thymocyte maturation the antigenic diversity of the T cell receptor is generated by a series of random gene rearrangements. After expressing antigen binding receptors, these cells are subjected to a selection process so that only T cells recognize antigenic peptides in the context of self-MHC molecules which are released from the thymus.
The thymus is divided into an outer cortex and inner medulla. The outer cortex contains many immature thymocytes which undergo rapid proliferation coupled with a large rate of cell death. The inner medulla is thought to contain thymocytes that are more mature.
A decline in immune functions that accompanies aging, leading to an increase in infections results primarily form changes in the T cell components of the immune system. The thymus reaches its maximal size at puberty and then atrophies, with a significant decrease in both cortical and medullary cells and an increase in the total fat content of the organ. Whereas the average weight of the thymus is 70 g in infants it is only 3 g in the elderly.
Secondary Lymphatic Organs
A naive immune cell is not able to mount an immune response until it has been activated to become an effector cell. Activation of a naive cell occurs in specialized microenvironments within secondary lymphoid tissue (e.g., peripheral lymph nodes, Peyer’s patches, tonsils, and spleen). Naive cells circulate indiscriminately to secondary lymphoid tissue by recognizing adhesion molecules on HEVs. High-endothelial venules (HEVs) which are special regions (such as those often found on postcapillary venules in the lymph node discussed below) which have specialized cells with a plump, high shape which express a variety of liked CAMs of the selectin family, within these microenvironments, dendritic cells capture antigen and present it to the naive lymphocyte, resulting in its activation.
The secondary lymphoid organs include the lymph nodes and spleen and mucosal associated lymphoid tissue. As blood circulates under pressure, the fluid component of the blood seeps through the thin wall of the capillaries into the surrounding tissue. Much of this fluid, called interstitial fluid, return to the blood through capillary membranes. The rest, called lymph, flows into a network of tiny open lymphatic capillaries and then into a series of progressively larger collecting lymphatic vessels. The largest lymphatic vessel, the thoracic duct empties into the left subclavian vein near the heart.
Louveau, “Structural and functional features of central nervous system lymphatic vessels” Nature, 2015) disclose that functional lympahtic vessels lining the dural sinuses are able to carry both flued and immune cells from the crebrospinal fluid and are connected to the deep cervical lymph nodes.
Lymph Nodes:Various lymphoid tissues are located along the vessels of the lymphatic system. For example, antigen are carried into lymph nodes by the lymph, it is trapped, processed and presented together with by resulting in . A lymph node is very efficient at trapping antigen carried into it by the afferent lymphatics.
Lymph nodes are organs which typically act as filters or traps for foreign particles. Like the spleen (see below) lyph nodes also house B cells. Lymph nodes are distributed widely throught the boyd including the armpit and stomach/gut and linked by lymphatic vessels. Chowdhury (14/380128)
Lymph nodes are found in clusters throughout the body and are composed of an outside cortex (which contains located within follicles and germinal centers) and inner medula (which contains antibody-producing plasma cells). lymphocytes enters via the afferent lymphatic channels and exits via the efferent lymphatic vessel. Blood borne lymphocytes also migrate into the node by passing between specialized endothelia cells that line postcapillary venules of the node.
–Germinal center (GC) is the microenvironment that allows the generation of B cell memory. There B cells proliferate and undergo somatic mutation, isotype switching, affinity selection, and differentiation into memory B cells or plasma blasts. The GC also contains T cells, follicular DCs, and GC DCs.
Lumph nodes contain mostly T cells.
Mucosa-associated lymphoid tissue (MALT): is the diffusion system of small concentrations of lymphoid tissue found in various sites of the body such as the gastrointestinal tract, thyroid breast, lung, salivary glands, eye and skin. MALT typically is involved in regulating mucosal immunity and ispopulated by lymphocytes such as T and B cells, as well as plasma cells and macrophages. The components of MALT are sometimes subdivided into the following: GALT (gut assocaited lymphoid tissue); BALT (bronchus-associated lymphoid tissue) and NALT (nose-associated lymphoid tissue) Chowdhury (14/380128).
Mucosa-associated lymphoid tissue (MALT), which is a network of lymphoid tissues that initiate immune responses against antigens encountered along these surfaces. MALT is a critical component of the secondary lymphoid system, along with organs like lymph nodes and the spleen, and includes specialized tissues such as the tonsils, Peyer’s patches (in the gut), and bronchus-associated lymphoid tissue (in the lungs).
–Epithelial Cells: The outcome of viral infections is determined by a series of intricate interactions between the pathogen and host. At mucosal surfaces like the respiratory tract (RT), epithelial cells lining the RT are not only the primary cell types that support the productive replication of IAV, but also serve as the first line of host defense against infection. The respiratory epithelial layer is a heterogeneous array of CD45- cells, including ciliated and non-ciliated airway lining cells and alveolar type I and II epithelial cells. Influenza infection of epithelial cells activates these resident cells by one or more distinct signaling mechanisms to produce type 1 interferons (IFNs) and a spectrum of inflammatory cytokines and chemokines. This, in turn, orchestrates the recruitment of innate and adaptive immune cells into the infected lungs, and modulates the function of these immune cells. See Braciale
–Microfold Cells: Specialized epithelial cells known as microfold cells (M cells) overlie the MALT and are able to translocate luminal material to basolateral antigen-presenting cells located immediately beneath the M cell. Since their initial discovery overlying Peyer’s patches of the gastrointestinal tract, M cells have been identified at other mucosal sites. Within the respiratory tract, M cells have been found in the upper and lower airways of both mice and humans. M cells express a number of pattern recognition receptors (PRRs). The majority of these M cell receptors have been identified on gastrointestinal M cells, while receptor expression by airway microfold cells is less well understood. Some PRRs on gastrointestinal M cells function in bacterial recognition and translocation. For example, the cellular prion protein (PrP(C)), a receptor for Brucella abortus, is necessary for B. abortus translocation. Similarly, glycoprotein 2 (GP2) expressed on the apical surface of gastrointestinal M cells recognizes FimH, a component of the type I pili found on both commensal and pathogenic bacteria. Mycobacterium tuberculosis (Mtb) can enter the body through multiple routes, including via specialized transcytotic cells called microfold cells (M cell). M cell transcytosis depends on the Mtb Type VII secretion machine and its major virulence factor EsxA. See Shiloh
Spleen: The spleen is a large 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 born antigens.
B cells generally originate from a common lymphoid progenitor and differentiate and develop within the bone marrow. Following maturation, B cells enter the circulation and peripheral lymphoid organs and tissue (e.g., spleen, lymph nodes and mucosa-assocaited lymphoid tissue (MALT) where they reside until needed. The spllen is an organ that has several functios, some of which are involed in the immune system. For example, the spleen hosues B cells. The spleen aslo removes antiobdy coated bacteria and antibody coated blood cell s by way of blood and lymph node circulations Chowdhury (14/380128)
The spleen contains two main compartments; an outer red pulp and inner white pup. These compartments are separated by a diffuse marginal zone. The white pulp surrounds the branches of the splenic artery, forming a periarteriolar lymphoid sheath (PALS), populated mainly by T lymphocytes. Blood borne antigens and lymphocytes enter the spleen through the splenic artery which empties into the marginal zone. In the marginal zone, antigen is trapped by interdigitating dendritic cells which carry it to the PALS.
The spleen contains a mixture of T and B cells and 10% macrophage and DCs.
Mucosal associated lymphoid tissue line the digestive, respiratory and urogenital system. The eptithelial cells of mucous membranes play an important role in promoting the immune response by delivering small samples of foreign antigen from the lumina of the respiratory, digestive, and urogenital tracts to the underlying mucosal associated lymphoid tissue. This antigen transport is carried out by specialized cells, called .
Diseases of the Lymphatic System
Lymphedema: also known as lymphatic obstruction is characterized by the stagnation and accumulation of excessive itnerstitial fluid, with accompanying swelling of subcutaneous tissues. It is a common and often devasting consequence of successful surgical and adjuvant therapy of breast cancer and other malignancies. In the US, the highest incidence of lymphedema is observed following breast cancer surgery, particularly among those who undergo radiation therapy following axillary lymphadenectomy. Among this population, 10-40% develop some degree of ipsilateral upper extremity lymphedema. The goal of conservative therpay is to eliminate protein stagnation and restore normal lymphatic circulation. These techiques are often cumbersome, uncomfortable and incovenient and include careful hygiene and antimicrobila therpay. Patients often wear compression garments and intermittent pneumatic pump compression therapy may also be instituted on an outpatient basis. Benzopyrenes, including flavonoids and coumarin, have been jused as adjunctive therpay but are not currently available for clinical use in the US. These drugs bind to accumulated interstitial proteins, inducing macrophage phagocytosis and proteolysis. The resulting protein fragments theorectially pass more readily into the venous capillaries and are removed by the vacular system. Lymphedema occurs with obstruction or functional inadequacy of lymph vessels. The resultatnt accumulation of interstitial fluid, containing high molecular weight proteins and other cellular debis, produces a condition with a complex biology that extends far beyond edema.