What type of tissue is the lymphoid system made of and what is special about it?
It is a specialized type of connective tissue that is considered to be the secnd hematopoietic tissue behind bone marrow.
What are the four groups of cells, tissues, and organs that make up the Lymphoid system?
The thymus, lymph nodes, spleen, and diffuse lymphatic tissue. The diffuse lymphatic tissue can be single nodules or aggregates of nodules such as the tonsils, appendix, and Peyer's patches.
What is the general function of the lymphoid system?
It is to monitor the body surfaces and compartments and react to potentially harmful substances that have crossed the epithelial barrier or have been transformed inside the tissue. It is the second line of defense after the neutrophils.
What is the major cell type of the lymphoid system?
Lymphocytes are the major effector cells of the system and are the key elements in immune response.
Where are the lymphocytes produced and what happens there?
They are made in the thymus and bone marrow and it is in these sites that they differentiate and mature. They are educated to destroy antigens here also. They are immunocompetent cells which means that they have the ability to distinguish between self and non-self cells.
What are the two types of responses that are provided by lymphocytes?
There is the humoral response which results in the production of antibodies by B-lymphocytes and plasma cells. These antibodies bind to antigens forming an AG/AB complex which is a marker for destruction by other immune cells. The other response is a cellular immune response, which targets the transformed or abnormal cells for destruction by the T-lymphocytes. This is the key method of immune response for protection against viral, bacterial, and fungal infections. It is also involved in the protection against invading tumor cells and is responsible for transplant rejection.
What happens to lymphocytes after they are made?
After they have been made, processed, and educated, they are transported by blood vessels to other places in the body.
What are the supporting cells and how are they organized?
They are the cells that assist the lymphoid organs and are either organized as a loose meshwork of reticular cells and reticular fibers as in the spleen, lymph nodes and nodules, OR they are organized in a structural meshwork of epithelioreticular cells in the thymus.
What are the two populations of lymphocytes?
There is the circulating pool which is about 70% of lymphocytes and these are the immunocompetnet cells as they migrate back and forth between the circulation and the lymphoid tissue to survey the surrounding tissues for foreign cells or material. The other 30% are the short-lived, immature cells or they are cells that are activated and destined for a particular tissue such as the connective tissue under the epithelium of the GI and respiratory tracts.
What is the first step of educating the lymphocytes and what is this phase called?
It is the "antigen-independent proliferation and differentiation" phase where they are genetically preprogrammed to recognize a single antigenic determinant. This happens in the bone marrow, thymus gland, and the primary lymph organs.
Where do the lymphocytes go after they differentiate?
After the differentiation, these cells then go to the lymph nodules and node, the tonsils, and the spleen through the blood circulation. These are the secondary lymphatic organs and here they undergo the second phase of education which is "antigen-dependent proliferation and differentiation". This is when they become effector lymphocytes and memory cells as they are introduced to the antigens.
What are memory cells and what is their function?
They are cells that do not participate in the initial response to an antigen, but they increase the circulating population of preprogrammed lymphocytes capable of recognizing an antigen. They help in starting a quick and more intense response when there is a secondary exposure to a foreign material. These memory cells are made as a result of the primary exposure.
What are the three groups of cells that lymphocytes can be classfied into?
There are the T-cells, the B-cells and the Natural Killer Cells.
What is the function of the T-cells, where are they made, where are they located, how long do they live, and how are they classified?
They are the ones involved in cell mediated immunity and they are produced in the thymus and become competent there. They are the majority of the circulating lymphocytes as they make up about 65-70% of the circulating pool of lymphocytes. They can be found in the periarterial sheaths of the spleen, the deep cortex of lymph nodes, and in internodular areas of the tonsils and Peyer's patches. They have a long life span and are sub-classified into three groups based on their surface markers.
What is the function of the B-cells, where are they made, where are they located, how long do they live, and what are the types?
They are cells that are involved in humoral immunity and producing antibodies or immunoglobulins. They are derived from bone marrow and become competent there and in the GALT (gut associated lymphoid tissue). They are found in the peripheral cortex of nodes and the nodular regions of the spleen, tonsils, and Peyer's patches. They have a variable life span and account for about 25% of the circulating pool. The effector B cell is the plasma cell which has lost its surface receptors and has stopped proliferating. B cells are also associated with follicular dendritic cells.
What is the function of the Natural Killer cells, where are they derived from, and what do they do?
They are genetically programmed to recognize the transformed cells. They are derived from the same precursor cells as B and T lymphocytes and represent the remaining 5 to 10% of the circulating pool. Once they recognize a foreign invader, they release substances such as fragmentins and perforins to create channels in the plasma membrane of cell to induce them to self-destruct. They essentially drill into the cell until it kills itself.
What is Diffuse Lymphoid Tissue and what is another name for it? Where are they located and why?
It is also known as MALT (mucosa associated lymphoid tissue) and is lymphoid tissue that is not encapsulated or is incompletely encapsulated by the connective tissue. The cells in this tissue are immediately beneath the lining epithelium in the lamina propia of the GI, GU, and Respiratory tracts because their lumens are exposed to the external environment. The cells are placed here strategically to intercept antigens and to initiate an immune response. They contact an antigen, they move to a lymph node in the region, proliferate and then differentiate. These new cells then return to the original location as the effector B and T cells. The tissues do not have a medullary or cortical region and they do not filter the blood or lymph.
What are lymphatic nodules, where are they located, what do they consist of and what do they look like?
These are localized concentrations of lymphocytes and are also found in the walls of the GI, GU, and respiratory tract. These are not encapsulated either but more sharply defined and recognizeable. They are aggregations of lymphocytes and are referred to as "follicles". If there are only small lymphcytes then it is a primary nodule. If the nodule has lymphocytes that have recognized antigens and have returned to the nodule to proliferate then it is a secondary nodule. These nodules are identified by light stained or pale "germinal center" which is in the center of the nodule. The large lymphocytes that are at the center and are proliferating have dispersed euchromatin hence the light pink color. Outside of this germinal center is the corona or the "mantle zone" which is made of the small lymphocytes.
What happens in the germinal center of the secondary lymphoid nodules? What else is present in the germinal center?
There is a cascade of events that goes from the proliferation of lymphocytes to the differentiation into plasma cells and then leads to antibody production. Additionally there is also an abundance of macrophages in the germinal center.
What are the aggregations of lymphatic nodules in the alimentary canal?
These are the tonsils and they form a ring of lymphatic tissue in the oropharynx. They are incompletely encapsulated and consist of aggregates of lymphatic tissue. The nodules do not have afferent vessels but do have efferent vessels for the drainage of the tonsil.
What are the tonsils that are in the lateral wall of the oropharynx, what are they made of, what are structural formations of importance, and what is clinically significant about them?
The aggregate tissue in the lateral wall of the oropharynx is between the palatopharyngeal and palatoglossal arches to make the "palatine tonsils." These are dense accumulations of lymphatic tissue that are under the mucous membrane or stratified squamous epithelium. The lymphoid tissue forms a band that contains free lymphocytes and nodules that are secondary as they have germinal centers. The epithelium dips into the connective tissue under it and forms the tonsillar crypts which are 10-20 in number. The lumens of these crypts have desquamated epithelial cells, live and dead lymphocytes, and bacteria. These crypts can have purulent spots in tonsilitis. Lastly, there is a band of dense connective tissue that encapsulates the tonsils and prevents it from spreading infections.
What are the tonsils that are in the superior and posterior portion of the roof of the pharynx? What is the structure of them?
These are the pharyngeal tonsils or the adenoids which are hypertrophied and chronically inflamed during an illness. The lymphatic tissue is covered by a respiratory epithelium with pseudostratified columnar cells with cilia and goblet cells. There are some areas that are covered with stratified epithelium also. It has lymphoid nodules and diffuse lymphoid tissue but without crypts and its capsule is thinner than a palatine tonsil.
What are the tonsils that are at the base of the tongue?
These are the lingual tonsils. They are made of lymphatic tissue that is covered by a stratified squamous epithelium of the tongue, they are smaller and more numerous, and each tonsil has ONE crypt.
What are the nodules that are concentrated in the ileum and what is their function?
These are Peyer's Patches and they have lots of B and T cells in the aggregations. They also have specialized pathogen sampling cells called M cells in the overlying epithelium. These cells do not have microvilli and instead they actively capture and transport antigens by pinocytosis from the intestinal lumen to the connective tissue where the antigen presenting cells and the B cells are located for the humoral response. The plasma cells then secrete IgA which is transported through the lining to the intestinal lumen. This antibody prevents the antigen from binding to other epithelial cells which would lead to infection.
What is the appendix's purpose and function?
It has a smooth mucosa with no plicae or villi. It has tubular glands that have a simple columnar epithelium. The lamina propria underneath this epithelium is heavily filled with lymphoid nodules. It is also covered with a serosa. It's main function is therefore lymphocyte response.
What are the three layers of the appendix?
It has a muscularis mucosae, submucosa, and muscularis externa which is an outer complete layer of longitudinal muscle.
What are the small lymphoid encapsulated organs?
These are the lymph nodes as they are encapsulated and bean shaped. They are along the course of the lymphatic vessels.
What is the function of the lymph nodes?
They are a series of in-line lymph filters that are important in the body's defense against microorganisms and the spread of tumor cells. They play a major role in the "mononuclear phagocytic system" because their main purpose is to be the "sites of antigen interaction with the immunocompetent cells."
What is the structure of the lymph nodes for where vessels and nerves enter and exit?
They have a convex surface for where the lymph vessels enter but a concave depression or hilum for where the arteries and nerves enter and for where the veins and lymphatic vessels leave.
What is the outer structure of the node leading inward?
The entire node is surrounded by a dense connective tissue capsule with extensions or trabeculae pushing into the parenchyma of the node. This area that the trabeculae push into is the subcapsular sinus and the trabecular lymphatic sinuses. The afferent vessels bring lymph to the node where they penetrate through the connective tissue capsule and enter into a trabeculae at different places along the convex surface of the node. Once inside the afferent vessels empty their contents into the "subcapsular sinuses." The remainder of the organ is made of reticular cells and fibers that make the supporting framework for the lymphocytes and other cells within the node. The reticular cells are stellate shaped with an oval nucleus and a small amount of acidophilic cytoplasm.
What are the two different types of cells in reticular tissue and what are their functions?
There are reticular cells that are can't be told apart from fibroblasts. These make and secrete Collagen Type III and the elongated cytoplasmic processes of the cell wrap around the reticular fibers to separate themselves from the lymphocytes. The other type are the follicular dendritic cells which are in the germinal centers between the B-lymphocytes. They have multiple cytoplasmic processes that are thin and hair like. The Ag/Ab complex bind to these processes and let the cells hold onto the antigen for many weeks or months.
What are the two parts of the parenchyma of the lymph node?
There is the medullary region and the cortical region.
Describe the cortical region of the lymph node parenchyma.
The cortex forms an outer ring of the node and has two parts. The peripheral region where the nodules , with or without the germinal centers, are. These are made mainly of B cells that are embedded in the population of the cortical cells. The deeper region is hte paracortical region that does not have boundaries nd is made up mainly of T lymphocytes and has high endothelial venules. This part is therefore thymus dependent, so if ther is a thymectomy done early in life then this part can be poorly developed. The cortex has a fairly dense meshwork of reticular fibers and cells.
Describe the medullary region of the lymph node parenchyma.
The medulla is the inner part of the lymph node and it has irregular cords of lymphatic tissue that are separated by lymphatic (meduallary) sinuses. These medullary sinuses connect to the trabecular lymphatic sinuses so that lymph moves from the periphery and percolates all the way to the center of the node. The sinuses are lined by endothelium that is continuous on the connective tissue side but discontinuous on the parenchymal side. The macrophages in the parenchyma can therefore stick their pseudopods into the sinuses to monitor the filtrate. The sinuses then join at the hilum and the majority of the lymphocytes that are located in this part are the B lymphocytes.
What takes the lymph away from the node?
Efferent vessels remove the lymph through the hilar region on the concave surface of the node.
Why can antigens enter the lymphatic system but not the circulatory system?
The lymphatic circulation begins with capillaries that are in the loose connective tissue and they remove fluid and substances fro mthe extracellular spaces to make the lymph. The walls of these vessels are more permeable than the capillary walls so the larger molecules like the antigens can enter the lymph stream.
How do lymphocytes from the lymph filter through the lymph node?
They enter the lymph node in the afferent lymphatic at the convex surface and the vessels cross the capsule and dump lymph into the subcapsular sinus. The lymph then goes through the intermediate sinuses into the medullary sinuses as they infiltrate the cortex and medullary cords for filtration.
How do lymphocytes from the blood enter the lymph node?
They come in through the wall of the post capillary endothelial venules that are lined with cuboidal or columnar epithelium. These "high endothelial vessels" are where the lymphocytes enter into the node. The walls of these vessels have receptors that can signal B and T lymphocytes that are primed with antigens to leave the circulation and go into the lymph node by diapedesis as is done by neutrophils.
What happens to the B and T cells once they enter?
The T cells are concentrated in the paracortex and are located around the lymphatic nodules whereas the B lymphocytes go to the medulla and nodules in the cortex.
What happens to the antigens in the node?
The antigens are trapped in the follicular dendritic cells and concentrated. They are processed and presented to the lymphocytes and this leads to an immune response.
What happens to the lymphocytes from the node?
Some of them pass through the node and leave through the efferent vessel at the hilum of the node. The afferent and efferent vessels both have valves to help with the unidirectional flow of lymph. The lymphocytes then eventually reach the thoracic duct and then the blood circulation to repeat the process.
What is the importance of the lymph node with respect to B cells specifically?
The lymph node is an important site for lymphocyte proliferation and transformation of B cells into plasma cells. As the plasma cells are made this also means that there are a lot of antibodies released, so the lymph leaving the nodes is usually rich with antibodies and the blood circulation eventually delivers these antibodies to the entire body.
What is the clinical significance of the lymph nodes?
One is that when malignant tumor cells reach the lymph nodes they can be distributed to other parts of the body by efferent lymph vessels and blood vessels. This is the process of metastasization. The second point is that satellite nodes get lymph from a specific part of the body and when there is an infection or antigenic stimulation, the nodes enlarge and are palpable. Lastly, inflamed nodules have multiple germinal centers with active cell proliferation which can be identified.
What is the thymus, where is it, and what does it do?
It is a primary immune organ that is involved in antigen independent lymphocyte production. It is a bilobed gland that is made form invaginated pharyngeal epithelium that migrates down to the superior mediastinum. The multipotential lymphoid stem cells that come from the bone marriow and are destined to become T lymphocytes migrate into the developing gland. The lymphoid cells then eventually squeeze into the spaces between epithelial celsl and that is how the thymus turns into a "lymphoepithelial organ of dual embryonic origin".
Describe the lifespan of the thymus and its structure.
It is fully functional and formed at birth and is present through the time of puberty. It has a high degree of organization as it has a capsule which has trabeculae which has lobules. There is a dense cortex and a lighter medulla. After puberty the T cell differentiation and proliferation decreases and the gland becomes filled with fat. It is restimulated to make T cells as necessary. It loses its morphology and still has a cortex and medulla plus Hassall's corpuscles.
Describe the capsule and the trabeculae of the thymus.
The capsule is a thin, dense connective tissue that has trabeculae penetrating into the gland to separate the gland into incomplete thymic lobules that are made of cortical caps over a highly convoluted medulla. The capsule and the trabeculae have blood vessels and efferent lymphatic vessels and nerves. However, there are NO afferent lymphatic vessels in the thymus.
Describe the cortex of the thymus gland.
It is made of densely packed lymphocytes that are extremely basophilic. The lymphocytes in this area are called thymocytes and since the cortex has more small lymphocytes it is darker. The thymocytes are in spaces that are around the epithelioreticular cells which are stellate shaped with light staining oval nuclei, have intercellular junctions and intermediate keratin filaments, and they are like the reticular cells and associated fibers in other lymphatic organs. There are also macrophages in the cortex that are responsible for phagocytosis of T cells that do not become educated. These macrophages therefore are programmed to die before leaving the thymus.
How many types of epithelioreticular cells are there and what is there distribution?
There are 6 with three in the cortex and three in the medulla.
Describe the medulla of the thymus gland.
It is the inner portion and it has epithelioreticular cells with loosely packed T cells. It stains lighter than the cortex because it has mainly large lymphocytes that have pale staining nuclei and lots more cytoplasm. Ne of the medullary epithlioreticular cells are the Type VI cells which make up Hassall's corpuscles. These are the characteristic feature of the thymus and are isolated masses of cells that have flat nuclei. They also have keratohyalin granules, bundles of intermediate filaments, and lipid droplets. The center of the corpuscle might look keratinized, its function is unknown, but they increase in number with age.
What is the purpose of the Blood-Thymic barrier?
It protects the developing thymocytes from exposure to antigens. The blood vesssels that pass from the trabeculae to the substance of the thymus carry a sheath of connective tissue and the thickness of the trabeculae is dependent on the size of the vessels. Additionally these vessels are ensheathed by epithelioreticular cells.
What are the five components of the barrier?
The capillary endothelium which is continuous and is highl permeable to macromolecules. The underlying basal lamina which is associated with the endothelium and is very thick with occasional pericytes, and this thickness prevents proteins/antigens from reaching the thymic cortex. The macrophages which are in the surrounding perivascular connective tissue to phagocytose any antigenic molecules that escape from the capillary lumen. The basal lamina of the epithelioreticular cells. Lastly the Type I epithelioreticular cells with occluding junctions that surround the capillary wall and provide more protection for the developing thymocytes.
What is the spleen?
It is the largest accumulation of lymphoid tissue in the body and it is the only one where lymph is interposed with the blood circulation. It acts as a blood filter to remove damaged RBC's and is a major defender against foreign material in the circulation.
What does the spleen store and what does it mature?
It stores platelets and it is where the lymphocytes are matured or activated and where the RBC's are matured.
What is the supporting tissue of the spleen and what does it do structurally?
It is dense connective tissue that encapsulates the spleen and extends trabeculae into the tissue to divide the parenchyma into incomplete compartments. These trabeculae carry nerves and arteries into the splenic pulp and the outgoing veins leave through the hilum. There are no lymphatic vessels in the splenic pulp though. THere are a few smooth muscle cells and myofibroblasts within the capsule and trabeculae that have contractile elements that help to discharge RBC's into the circulation. The remainder of the supporting tissue or stroma of the spleen is made up of reticular tissue, lymphoid cells, and macrophages.
What are the two parts of the parenchyma of the spleen?
There is the white and red pulp. The white pulp has lymphoid aggregations that are basophilic areas because of dense heterochromatic in the lymphocytes. The branches of the splenic artery go through the capsule and into the trabeculae to make trabecular arteries which then enter the white pulp and become the central arteries. The T lymphocytes then aggregate around the central arteries to make periarterial lymphatic sheaths (PALS). The PALS are therefore thymus dependent zones. The central artery is what helps tell the difference between PALS and nodules. B cells are in the nodules and the presense of germinal centers helps determine if there is a response to antigens.
What is the marginal zone of the spleen?
It is between the whtie and red pulp. It is made of loose lymphatic tissue and many blood sinuses. It has active macrophages and this is because there is an abundance of blood antigens found here.
Describe the red pulp.
It is the bulk of the organ and is highly vascular. It is made of elongated cords of cells called Billroth's cords that are between the splenic sinuses which are lined by elongated endothelial cells. The long axis of the cells is parallel to the sinusoids and these cells are enveloped in reticular fibers. The fibers are perpendicular to the long axis of the sinusoid. The perpendicular directions makes a meshwork that supports the sinusoidal cells and the macrophages. The Billroth's cords also have erythrocytes, granulocytes, lymphocytes, plasma cells, and macrophages that are involved in hemoglobin breakdown and iron reclamation.
Describe the splenic circulation inward.
Blood enters through the splenic artery which branches wihin the capsule into the trabeculae to make trabecular arteries. These branch within the parenchyma of the cell. Some of these make central arteries which are surrounded by T cells are referred to as PALS. Each central artery gives off branches at right angles called penicillary arteries. The PA's end as sheathed capillaries which are blind ending capillaries without endothelial lining and are surrounded by macrophages before entering the red pulp.
Describe the splenic circulation outward.
The splenic parenchyma is permeated by sinuses which drain into the larger sinuses or trabecular veins and then drain into the splenic vein which drains into the portal vein. The sinuses are surrounded by flattened endothelial cells that have numerous slits in its basement membrane.
What is the theory of closed circulation?
It is the theory that the arterial capillaries open directly into the sinusoids within the spleen and so the blood is always within a vessel.
What is the theory of open circulation?
It is the theory that blood passes through the spaces between the red pulp and moves toward the sinusoids where it is collected. The defective RBC's cannot pass through the slits of the sinusoidal basement membranes and there are non-filtering areas where the T and B lymphocytes are located to support this theory.