Lymphoid organs and lymphoid-associated tissue

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The lymphatics drain the tissues to the lymph nodes. Where do these then drain to in the vascular system?	Out through the lymphatic duct in the left subclavian vein into the right atrium.
Antigen is transported into lymph nodes via the afferent lymphatics - which cells tend to be transporting the antigen from the tissues?	Dendritic cells.
Which lymphocytes are found in the follicles of lymph nodes?	99% B cells!
Are the T cell zones of lymph nodes more superficial or more deep than the follicles?	More superficial, nearer the cortex.
Which immune cells does the afferent blood supply bring to the lymph nodes?	Naive B and T cells.
Which immune cells does the efferent blood supply transport away from the lymph nodes?	Effector cells
What are the B cells in the follicles and the T cells in the T cell zones doing in there?	Waiting to be stimulated, activated, and matured/differentiated by antigen.
What are the primary (central) lymphoid organs?	The thymus and bone marrow. Where maturation of lymphocytes takes place. Immature lymphocytes generated in haematopoiesis mature and become committed to a particular antigenic specificity within the primary lymphoid organs (e.g. B or T). Only after a lymphocyte has matured within a primary lymphoid organ is it deemed immunocompetent.
What are the secondary (peripheral) lymphoid organs/tissues?	The lymph nodes, spleen, and mucosa-associated lymphoid tissues (MALT) e.g. gut, nasal, bronchus, tear duct etc. These organs provide sites for mature lymphocytes to interact with antigen.
What is the lymphatic system?	A network of vessels that collect fluid that has escaped into the tissues from capillaries of the circulatory system. Ultimately, this escaped fluid is returned to the blood (mostly via the left subclavian vein, through the thoracic duct, but those vessels draining the right arm and right side of the head converge to form the right lymphatic duct, which empties into the right subclavian vein).
Which secondary lymphoid tissues are found in the pharyngeal area?	The tonsils and adenoids.
Where are Peyer's patches found in the body?	In the jejunum, the middle section of the small intestine.
Where in the body is the thymus found?	A flat, bilobed organ situated above the heart, the thymus is the site of T-cell development and maturation.
Describe the organisation of the lobes of the thymus.	Each lobe is surrounded by a capsule and divided into lobules, which are separated from each other by strands of connective tissue called trabeculae. Each lobule is organised into two compartments: the outer compartment, or cortex, is densely packed with immature T cells, called thymocytes, whereas the inner compartment, or medulla, is sparsely populated with thymocytes. In the medulla, Hassall's corpuscle of concentratic layers of generating epithelial cells are found, as well as macrophages and dendritic cells from the bone marrow.
Many of the stromal (epithelial, dendritic, macrophage) cells that make up the framework and contribute to the growth and maturation of thymocytes also interact physically with them. What is the function of the thymus?	The function of the thymus is to generate and select a repertoire of T cells that will protect the body from infection. As thymocytes develop, an enormous diversity of T-cell receptors is generated by gene rearrangement, which produces some T cells with receptors capable of recognising antigen-MHC complexes. However, most of the T cell receptors produced by this random process are incapable of recognising antigen-MHC complexes, and a small portion react with combinations of self antigen-MHC complexes. The thymus induces death of those T cells that cannot recognise antigen-MHC complexes and those that react with self-antigen MHC strongly enough to pose a danger of causing autoimmune disease. More than 95% of all thymocytes die by apoptosis in the thymus without ever reaching maturity.
When does the thymus reach its maximum size and begin to atrophy?	In puberty.
What is lost and what is gained when the thymus atrophies?	Both cortical and medullary cells are lost, while fat content is gained. This loss of mass also results in a loss of T cell production.
What is the average weight of the thymus in a child? And in an elderly individual?	30g in a child, 3g in the elderly individual - as a result of loss of cell mass and gain of fat content.
By the age of 35, what percentage of the newborn's thymic generation of T cells dropped to? And at age 65?	At age 35: 20% the rate of newborn production. At age 65: 2% the rate of newborn production.
Thymic function declines with which inevitable physiological process...?	Age
Bone marrow is both the site of haematopoiesis and a fat depot. Fat eventually fills what percentage of the marrow compartment of bone?	50% or more
What is the function of bone marrow stromal cells with regard to B lymphocytes?	Stromal cells within the bone marrow interact directly with the B cells and secrete various cytokines that are required for development.
Bone marrow B cells are the source of what percentage of IgG and IgA in plasma?	~90%
As with T cell maturation, there is a selection process within the bone marrow that eliminates B cells that possess what?	Self-reactive antibody receptors.
Why does the body require a lymphatic system to return lymph to the circulation?	Blood circulating under pressure results in plasma seeping through the thin walls of capillaries into the surrounding tissue.
How much lymph must be returned to the circulation in a day?	In an adult, depending on the size and activity, seepage can add up to 2.9 litres or more during a 24-hour period.
What is the proper name for lymph and what is its function?	Interstitial fluid permeates all tissues and bathes all cells.
What would develop if the lymphatic system did not return interstitial fluid to the circulation?	If this fluid were not returned to the circulation, oedema, a progressive swelling, would result and eventually become life threatening. This is not the case because much of the fluid is returned to the blood through the walls of venules, and the remainder is returned via primary lymphatic vessels.
What is the composition of the walls of the primary lymphatic vessels?	The walls of the primary vessels consist of a single layer of loosely apposed endothelial cells. Their porous architecture (sinusoid) allows fluids and even cells to enter the lymphatic network.
What is the largest lymphatic vessel?	The thoracic duct, which empties into the left subclavian vein.
The heart does not pump lymph through the primary and major lymphatic vessels. What results in its movement?	Instead, the slow, low-pressure flow of lymph is achieved as the lymph vessels are squeezed by movements of the body's muscles. A series of valves along the lymphatic vessels ensures that lymph flows only in one direction.
How does lymph interact with lymphoid organs/lymphocytes?	When a foreign antigen gains entrance to the tissues, it is picked up by the lymphatic system and is carried to various organised lymphoid tissues such as lymph nodes, which trap the foreign antigen. In the organised lymphoid tissues, the lymphocytes can interact with trapped antigen and undergo activation.
Before it is activated, what is the composition of a lymphoid follicle/primary follicle?	Until it is activated by antigen, a lymphoid follicle (a primary follicle) comprises a network of follicular dendritic cells and small resting B cells.
After activation, what happens to lymphoid/primary follicles?	After an antigenic challenge, a primary follicle becomes a larger secondary follicle, a ring of concentrically packed B lymphocytes surrounding a centre (a germinal centre), in which one finds a focus of proliferating B cells and some helper T cells interspersed with macrophages and follicular dendritic cells.
What is a germinal centre (in a follicle)?	Germinal centre: a region within lymph nodes and the spleen where B-cell activation, proliferation, and differentiation occurs. Germinal centres are sites of intense B cell somatic mutation and selection.
Where are lymph nodes found?	Throughout the tissues, they are clustered at junctions of the lymphatic vessels and are the first organised lymphoid structure to encounter antigens that enter the tissue spaces.
What are the three morphological regions of a lymph node?	The medulla, the paracortex, and the cortex.
What is found in the cortex of a lymph node?	This contains lymphocytes (mostly B cells), macrophages, and follicular dendritic cells arranged in primary follicles. After antigenic challenge, the primary follicles enlarge into secondary follicles, each containing a germinal centre. In children with B cell deficiencies, the cortex lacks primary follicles and germinal centres.
What is found in the paracortex of a lymph node?	Beneath the cortex, this is populated largely by T lymphocytes and also contains dendritic cells that migrates from tissues to the node. These dendritic cells express high levels of class II MHC molecules, which are necessary for presenting antigen to TH cells.
Which cells are found in the medulla of a lymph node?	This is more sparsely populated with lymphoid lineage cells than the cortex and paracortex, and of those present, many are plasma cells actively secreting antibody molecules.
What are the cellular responses within a lymph node when antigen is carried into it?	It is trapped, processed, and presented with class II MHC molecules by dendritic cells in the paracortex. This results in the activation of TH cells. The initial activation of B cells takes place within the T-cell rich paracortex. Once activated, TH and B cells form small foci consisting largely of proliferating B cells at the edges of the paracortex. Some B cells within the foci differentiate into plasma cells secreting antibody. These foci reach maximum size within 4 to 6 days of antigen challenge. Within 4 to 7 days of antigen challenge, a few B cells and TH cells migrate to the primary follicles of the cortex, where cellular interactions between follicular dendritic cells, B cells, and TH cells take place, leading to development of a secondary follicle with a central germinal centre. Some of the plasma cells generated in the germinal centre move to the medullary areas of the lymph node, and many migrate to bone marrow.
In the event of an infection or other introduction of antibody to the host, antigen is carried via afferent lymphatics to the lymph nodes. What two things does efferent lymph have a higher concentration of, in this situation, than afferent lymph?	Antibodies newly secreted by medullary plasma cells, and a 50x higher concentration of lymphocytes.
What, as well as lymphocyte proliferation within the lymph node, contributes to a greater concentration of lymphocytes in the efferent lymphatic vessels than the afferent lymphatic vessels during an infection?	most of the increase represents Blood-borne lymphocytes that enter the node by extravasation between high endothelial cells (HEVs; unusually plump cells lining postcapillary venules). Because antigenic stimulation within a node can increase extravasation of lymphocytes into the node 10-fold, the number of lymphocytes in a node that is actively responding can increase greatly and the node swells visibly. Factors released in lymph nodes during antigenic stimulation are thought to facilitate this increased migration.
What is the immune function of the spleen?	It plays a major role in mounting immune responses to antigens in the blood stream. Whereas lymph nodes are specialised for trapping antigen from local tissues, the spleen specialises in filtering blood and trapping blood-borne antigens; thus, it can respond to systemic infections.
Antigens are not supplied to the spleen by the lymphatic vessels - so how do they get there?	In the blood supply of the splenic artery.
True or false: More recirculating lymphocytes pass daily through the spleen than through all the lymph nodes combined?	True!
The spleen is surrounded by a capsule from which a number of projections (trabeculae) extend into the interior to form a compartmentalised structure. The compartments are of two types, the rep pulp and white pulp, which are separated by a diffuse marginal zone. What do the red and white pulp do?	The splenic red pulp consists of a network of sinusoids populated by macrophages, numerous red blood cells, and few lymphocytes; it is the site where old and defective erythrocytes are destroyed and removed. Many of the macrophages within the red pulp contain engulfed erythrocytes or iron-containing pigments from degraded haemoglobin. 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 centres. The marginal zone, peripheral to the PALS, is populated by lymphocytes and macrophages.
In the marginal zone, which leukocytes capture antigen and carry it to the periarteriolar lymphoid sheath (PALS)?	Dendritic cells!
Where in the spleen does the initial activation of B and T cells occur?	The periarteriolar lymphoid sheath (PALS).
In the PALS, dendritic cells present antigen via MHC II molecules to T-helper cells. Which cells do these T-helper cells activate and migrate to the primary lymphoid follicles of the spleen with?	B cells!
What are the immune consequences of losing the spleen?	The severity of consequences if the spleen is lost depends on the age at which splenectomy takes place. In children, splenectomy often leads to an increased incidence of bacterial sepsis caused primarily by Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. Although fewer adverse effects are experienced by adults, splenectomy does lead to some increase in blood-borne bacterial infections (bacteraemia).
List the four types of mucosa-associated lymphoid tissue that protect the combined mucosal surface area of around 400 m^2.	Bronchus-associated lymphoid tissue, gut-associated lymphoid tissue, lacrimal-associated lymphoid tissue, and nasal-associated lymphoid tissue. BALT, GALT, LALT, and NALT. As well as the tonsils and appendix.
What is the range of structures/compositions that MALT may consist of?	From loose, barely organised clusters of lymphoid cells in the lamina propria of intestinal villi to well-organised structures such as Peyer's patches, which are found within the intestinal lining.
True or false: the number of antibody producing plasma cells in the mucosa-associated lymphoid tissue far exceeds the combined numbers in the spleen, lymph nodes, and bone marrow?	True! A testament to how critical its presence is.
Which type of immune cells does the epithelium of the MALT mucosa contain? And the lamina propria?	MALT epithelium: intraepithelial lymphocytes, many of which are T lymphocytes. MALT lamina propria: B lymphocytes + plasma cells, activated T helper cells, and macrophages. Histologic sections have revealed more than 15,000 lymphoid follicles within the intestinal lamina propria of a healthy child!
Which type of cell in the epithelium facilitates the presentation of antigen from the lumina of the respiratory, intestinal, urogenital, and lacrimary glands to the lymphocytes in MALT?	M cells - these are flattened epithelial cells lacking the microvilli that characterise the rest of the mucous epithelium. M cells have a deep evagination in the basolateral plasma membrane, which is filled with a cluster of B cells, T cells and macrophages. Antigens in the intestinal lumen are endocytosed into vesicles that are transported from the luminal membrane to the underlying pocket membrane. The vesicles then fuse with the pocket membrane, delivering the potentially response-activating antigens to the clusters of lymphocytes and antigen-presenting cells present, the most important of which are dendritic cells, contained within the pocket. Antigen transported across the mucous membrane by M cells ultimately leads to the activation of B cells that differentiate and then secrete IgA. This class of antibody is specialised for secretion and is an important tool used by the body to combat many types of infection at mucosal sites.
Peyer's patches nodules, which extend from the subepithelium to the muscle layer in mucosa, contain how many lymphoid follicles each which can differentiate into secondary follicles with germinal layers?	30-40 lymphoid follicles
What type of dendritic cell is scattered about the epithelial cell-matrix of the epidermis?	Langerhans cells, which internalise antigen by phagocytosis or endocytosis before undergoing activation and maturation and migrating to regional lymph nodes, where they activate naive T-helper cells.
Other than Langerhans cells, which other immune cell type is found in the epidermal layer of the skin?	Intraepithelial lymphocytes (mostly T cells).
Which immune cell types are found in the dermal layer of the skin?	T cells and macrophages.
Lacrimal-drainage associated lymphoid tissue is a relatively recent discovery. What features of the tissue helped to clarify its function as part of MALT?	LDALT was found as a result of lymphomas in efferent tear ducts having typical features of lymphomas arising in MALT. The presence of lymphocytes and plasma cells as a diffuse lymphoid tissue in the lamina propria was noted, together with intraepithelial lymphocytes and occasional high endothelial venules (HEVs). The majority of lymphocytes were T cells, whereas B cells were interspersed individually or formed follicular centres. Primary and secondary lymphoid follicles possessing HEV were present in about half of all specimens.

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