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Antigens only recognize antibodies, if they are bound by the MHC-complex. In contrast soluble antibodies are recognized only if they are present by specific cells. It is unclear if these specific cells are T-cells. A new study shows that not only educated T-cells have been exported by the thymus, but also precursor cells migrate to the gut, where they mature to lymphocytes.
The lymph nodes have different compartments. For one thing they have a cortex with germinal centres and more or less follicular (B-cell area) and for another thing a paracortex indentified by a large number of T-cells and high endothelial venules. Furthermore they have a medulla where lymphocytes immigrate to efferent lymphatics. The site of exit is unknown.
To show the differences, a transplantation experiment was made during the course of studies to put the pLN into mLN: The pLN was reconnected with the blood stream and the afferent lymphatics. The resident immune cells from the pLN were replaced by host immune cells. Follicle dendritic cells (FDC), follicle reticular cells (FRC) and lymphatic endothelial cells (LYVE) remained within the regenerated lymph nodes and the original stroma cells of the pLN formed the regenerated lymph node.
It can be derived that stroma cells are side-specific. The functions of stroma cells can be explored by the experiment mentioned above. Stroma cells originated by regenerated pLN are not able to induce RALDH2 ( a mediator of vitamin A) expression, which is responsible for CCR9 and other chemokines.
All the lymph nodes have similar architecture and operate on the same basis. But nevertheless, the quality of the immune responses can be modified.
The stroma cells contribute the structure of lymph nodes and the flow of immune cells by producing chemokines, cytokines and adhesions molecules, whereby the immune response is being influenced, too.
Furthermore are there native-antigen cells which patrol through the lymph node continuously. At first they circulate with the blood stream, do enter subsequently the lymph node via high endothelial venules and do continue with scanning of cells presenting antigens. The backbone of the lymph node is the three-dimensional-network, the conduit system. Thereby, each different lymph node shows a unique function. Differences in the lymph nodes might arise during their development.
The exact number of lymph nodes is still unknown in humans. Scientists reckon nearly 500-700 different lymph nodes. The length and diameter of many lymph nodes are only a few millimetres.
The differences of the lymph nodes dependent on stroma cells. Also differences can be derived from the skin draining mesenteric lymph node and the gut draining lymph node. Transplantation experiments of lymph nodes and dendritic cells show, that regional stroma cells differ in their ability to support mucosal tolerance, the induction of tissue tropism and humoral immunity.
In conclusion, stroma cells induce tissue-specific immune responses and fit lymph nodes with unique functional properties.
Unfortunately, studies were hampering by difficult isolations of stroma cells. But owing to the intra-vital microscopy we can visualize cellular interactions on animals alive.
Furthermore, the mesenteric lymph nodes have a number of unique phenotypical and functional properties, i.e. a strict development. At first, the MAdCAM-1 expression rises to high endothelial venules followed by the induction of gut homing on activated lymphocytes and the generation of intestinal tolerance ensues. Some properties can produce in vitro by special immune cell populations which have to be isolated. Differences in the stroma compartments during organogenesis are a result of signals originated by a drained area.
Afterwards there are main differences between all the structures of the different lymphoid structures (encapsulated or diffusely bordered, route of antigen to the organ; exit and entry side; environmental and age effects; founding on other specific sides, others are induced by i.e. microbial factors). So the primary lymphoid organs (thymus and bone marrow) produce the B- and T-lymphocytes independent of antigens. Additionally, the volume of the organs will only change if our body will get an infection. Post infection organs will shrink to their normal volume. The B-cells will come into being in the bone marrow but differ from the way of building of T-cells in the thymus. The exact way of B-cell emergence is not known. During the development of the lymph nodes human lymphoid precursor cells enter the thymus very early. Afterwards the cells differentiate and show clonal expansion and do form T-cells and develop tolerance with respect to the body. Also T-cell differentiation arise before birth and postnatal in humans. The maximum size of the thymus will be reaches in puberty.
Also the secondary and tertiary lymphoid organs have special structures and functions. The secondary lymphoid organs like the spleen and tonsils do react on special infections.
The spleen is a well-structured capsule with a white and red pulp. The white pulp is similar to the lymph nodes and the red pulp is different to them. It's clearing senescent red cells, particles, encapsulated bacteria and protozoa.
The tonsils are typical secondary organ, too. They do neither have real capsules nor afferent lymphatics but a special epithelium. Tonsils studied by transplantation experiments. The size of them is age-dependent. Some tonsils are predominant for some infections in certain ages. The surface area is enlarged by crypts with reticular epithelium with specific cells for antigens. As well as the other lymphoid organs tonsils have defined compartments like the follicular area with a majority of B-cells in follicle and germ centres, a para follicular area with T-cells and high endothelial venules for entry and the efferent lymph drained into cervical lymph nodes.
1996 scientists detected cryptopatches in a mouse. It is speculated if cryptopatches are a third primary organ, because there are not enough studies about cryptopatches. Cryptopatches are clusters of about 1000 cells situated around intestinal crypts (epithilal hollow in the mucosal and arranged in several layers). They have not many B- and T-cells. Thereby the chemokine Interleukin-7 (in intestinal epithelium) stimulates the development of cryptopatches. Additionally they can be found in mice without B- and T-cells and are present in germfree mice, too.
The main function is the formation of intraepithelial lymphocytes. Cryptopatches are not studied in other mucosal epithelium like in the trachea.
Also discussed is the existence of hemal nodes. They show small lymphoid structures with a capsule. They are filled with erythrocytes. Because of this they get a red colour. Additionally hemal nodes have high endothelial venules and efferent lymphatics, but no afferent lymphatics.
Furthermore, use of the expressions "Lymphoid tissue" and "Lymphoid organs" is to be carefully chosen: Often they are put at the same level, but an organ is a defined structured assembly of tissue forming a functional unit like the spleen; Tissue are special cells in a specific area only.
Finally, it is important to look at all the phases of immune responses with their special chemokines. Important roles play the T- and B-cells which interact in a variety of ways. The T-cells were generated in the thymus early and then circulate through the secondary lymphoid organs where they will be show their activation. B-cells modulate the chemokine receptors in the early state of immune responses namely the interaction with T-cells in the T-B-border.
An effective immune response depends on the specialized organization and interaction of the secondary lymphoid organs. For example the inducer cells, the native cells of lymphocyte cells, activate special chemokines (CCL21 and CXCL13), which help by the definition of T-and B-cell regions. Majority of chemokines in tissues have a low concentration and only decrease soon after an inflammation.
After the effective immune response most of the effectors cells will be dying. This will be induced by special antigens. The cells which will be survived are called memory or stem cells. This will be prepared the body for the next infection. Also the surviving cells will be controlled by different chemokines.
In the nearly future the Scientists will be research the context about the immune system more exactly. Especially the regeneration of lymph nodes in vitro and in vivo is the purpose for the Scientists. This will be a future prospect for the cure of lymph node cancer or other lymph nodes diseases.
I will hope that these researches will be crowned with success.