User talk:Zeeladeshra/sandbox

The lymphatic endothelium is a specialized form of epithelium and is found lining the vasculature of the lymphatic system. The first study of a pure culture of lymphatic endothelial cells can be dated back to the early 1980s, where lymphatic endothelial cells from a patient were isolated.

Structure
The lymphatic endothelium contains flattened endothelial cells, which are also characterized as simple squamous cells. The characteristics of these endothelial cells is crucial in helping the lymphatic system carry out its function as a system involved in the absorption of tissue fluids and particles. In contrast to blood capillaries, lymphatic vessels have wider lumens to accommodate for the large influx of fluids and particles across the endothelium.

The lymphatic endothelium contains many overlapping intercellular junctions due to the superimposition of the lymphatic endothelial cells. These junctions allow for the efficient flow of tissue fluids and particles through the endothelium.

The pressure gradient across the endothelium allows for the opening and closing of these intercellular junctions. When there is an increase in interstitial fluid pressure, the junctions of the lymphatic endothelium will open and allow fluids and particles to flow through the lymphatic endothelium and into the lumen of the lymphatic vessels. As the fluid enters the lumen of the vessel, the interstitial fluid pressure will decrease and cause the intercellular junctions to close, preventing any retrograde flow of fluids and particles back out into the interstitial space.

The endothelium is involved in fluid and particle uptake, as such it is important for the lymphatic vasculature to maintain its shape and composure throughout fluid and particle uptake. One of the key characteristics of the lymphatic endothelium which allows it to maintain its shape despite changes in interstitial pressure, is its ability to attach to interstitial collagen via anchoring filaments.

These anchoring filaments are composed of elastin fibres which allow the lymphatic vessels to maintain their composure throughout fluctuations in interstitial pressure. By preserving their functionality, the elastin fibres prevent the lymphatic vessels from collapsing.

Molecular Characterization
Several molecular markers are required for the proper development of the lymphatic endothelium and ultimately the lymphatic system. The three most important markers that are involved are VEGF-C, VEGF-D and Ang2. VEGF-C and VEGF-D are both ligands for their respective receptor, VEGFR-3.

By binding to this receptor, they are able to activate the process of lymphangiogenesis.

Immunological Response
The lymphatic vessels allow for leukocytes to be recruited from their peripheral sites and trafficked to their respective draining lymph nodes. As such, the lymphatic endothelium which lines the lymphatic vessels plays a crucial role in both the adaptive immune response as well as the innate immune response. The lymphatic endothelial cells ensure that cellular mediators of the immune response are brought to the lymph vessels and drained effectively into the lymph nodes.

Lymphatic endothelial cells are able to express chemokines on their surface, which will attract certain cellular mediators of the innate immune response, such as dendritic cells, monocytes, basophils and neutrophils. CCL21 is a specific chemokine that is expressed by lymphatic endothelial cells, this chemokine attracts dendritic cells. Dendritic cells have a receptor on their surface called CCR7, which will bind to the CCL21 chemokine that is expressed on the lymphatic endothelial cell.

An antigen-specific adaptive immune response allows for the upregulation of certain cell adhesion molecules such as, ICAM-1 and E-selectin. These cell adhesion molecules are also expressed on lymphatic endothelial cells. The upregulation of these cell adhesion molecules is synergistic with the expression of chemokines like CCL21 on the surface of lymphatic endothelial cells. All of these processes together, will recruit cellular mediators like dendritic cells towards the lymph vessels. Once recruited, the cellular mediators are able to transmigrate across the lymphatic endothelial cells and move towards the lymph nodes through the help of cell adhesion molecules. This process is crucial during antigenic challenges that arise in the body, as it creates an efficient and effective immune response.