Immune System and Lymphatic Tissue

Objectives

Identify lymphoid tissue and lymphoid nodules.
Describe the morphological features of tonsils, lymph nodes, spleen and thymus.
Describe location, structure, and general function of each organ listed above.

Overview

The immune system functions to defend the body against infectious and pathogenic agents, foreign substances, and transformed cells and their products. The lymphatic system consists of organs, vessels, and cells that serve as the counterpart of the immune system that monitors the external and internal body. Lymph tissue is particularly prevalent in the gastrointestinal tract and the respiratory system, which are both open to the outside world and constantly bombarded by pathogenic microorganisms.

The lymphatic system can be divided into primary and secondary structures:

Primary lymph organs produce special immune cells
- Thymus
- Bone Marrow
Secondary lymph organs are where the cells function
- Lymph nodes and associated lymphatic vessels
- Spleen
- Tonsils (pharyngeal, or adenoids, palatine, and lingual tonsils)
- Gut-associated lymph tissue (GALT)
- Mucosa-associated lymph tissue (MALT)
- Appendix

Cells of the Immune System

Almost all immune system cells are derived from hemopoietic stem cells (HSCs) in bone marrow. An overview of this cell development pathway can be found in the Blood and Bone Marrow page.

Lymphocytes are produced and mature in primary lymph organs before migrating to secondary lymph organs. They are identified by clusters of differentiation (CD) markers found on the surface of the cell.
- B cells arise in bone marrow and differentiate in peripheral lymph tissue into plasma cells and memory B cells. They account for 20-30% of circulating lymphocytes. Specialized B cells (thymic B cells) reside in thymus.
- T cells differentiate in the thymus into T-helper cells, cytotoxic T-cells or regulatory T-cells. They account for 60-80% of circulating lymphocytes.
- NK (Natural Killer cells) cells arise in bone marrow and differentiate in peripheral lymph tissue. They account for 5-10% of circulating lymphocytes.
Supporting Cells interact with lymphocytes by presenting antigens and help regulate immune response and are arranged in a loose meshwork of lymph nodules, lymph nodes, and the spleen. These include:
- monocytes, macrophages, neutrophils, basophils, mast cells, eosinophils, reticular cells, dendritic cells (DCs), follicular dendritic cells, Langerhans cells, and epithelioreticular cells.

Lymphatic Tissue and Organs

Lymphatic Vessels

Lymphatic vessels begin as a network of capillaries in loose connective tissue. They remove fluid and substances (lymph) from the extracellular space that is not picked up by venules. The walls of lymphatic capillaries are more permeable than blood capillaries, thus, larger molecules like antigens enter the capillaries. Lymphatic capillaries become lymphatic vessels and carry lymph fluid and lymph cells through lymph nodes. Lymphatic vessels closely follow the venous pathway and lead to the largest lymphatic vessel, the thoracic duct and the other main channel, the right lymphatic duct. Ultimately, lymph drains to these 2 channels and then into the venous system at the junctions of the internal jugular and subclavian veins on the left and right side of the body. Lymphatic vessels consist of endothelium but lack a continuous basal lamina, resulting in more permeability comparted with blood vessels. Lymphatic vessels contain valves to prevent backflow of lymph.

Lymph Nodes

Lymph nodes are bean-shaped, encapsulated organs that are found along the lymphatic vessel pathway and can be clustered in regions including the groin, neck, axilla, and mesenteries. Their structure consists of a superficial and deep cortex and medulla. Afferent lymph vessels carry lymph and lymphatic cells into the node at various points around the peripheral surface. The efferent lymph vessel carries lymph away from the node at the hilum (concave surface where blood vessels enter and exit).

Structure:
- Capsule of dense connective tissue
- Trabeculae of dense connective tissue which extend from the capsule into the node, creating a framework
- Reticular tissue composed of reticular cells, fibers, and ground substance that creates a meshwork
- Lymphatic sinuses– create channels in through the lymph node
- Lymphatic nodules– found in the superficial cortex; primary nodules consist of mainly small lymphocytes and secondary nodules contain a germinal center
  - Germinal centers- where B lymphocytes divide and proliferate upon antigen recognition
- High Endothelial Venules– entry point where lymphocytes enter lymph node from blood vessel

Cells:
- Reticular cells- similar morphology to fibroblasts, secrete type III collagen/reticular fibers
- Dendritic cells (DCs)- bone-marrow-derived, antigen presenting cells, usually found in T-lymphocyte rich areas
- Macrophages- phagocytic and antigen-presenting cells
- Follicular dendritic cells (FDCs)- found in the germinal centers and contain cytoplasmic processes that pass between B lymphocytes
- B cells- found mainly in superficial cortex
- T cells- found mainly in the deep cortex

Figure 14.17 and 14.21. Histology: A Text and Atlas: With Correlated Cell and Molecular Biology, 8e, 2020. Copyright © Wolters Kluwer

Diffuse Lymphatic Tissue

Lymphatic tissue and nodules can be found throughout the body, especially in the gastrointestinal tract, respiratory passages and genitourinary system. Accumulations of lymphocytes can be found in the lamina propria, known as MALT. Nodules are more organized and described above. Along with being found in lymph nodes, they can also be found in these passages including tonsils and in the gastrointestinal tract, they are referred to as GALT.

Thymus

The bilobed thymus is located in the superior mediastinum just posterior to the upper sternum and anterior to the great vessels. It is fully formed and functional at birth but undergoes involution beginning at puberty. Much of the organ is slowly replaced by adipose tissue.

Structure:
- Capsule– thin layer of connective tissue with trabeculae that extend into the parenchyma. Contains blood vessels, efferent lymph vessels, and nerves
- Cortex– basophilic due to the developing T lymphocytes and scattered macrophages; associated with Type I, II, and III epithelioreticular cells
- Thymic lobules– established by the trabeculae
- Medulla- contains Type IV, V, and VI epithelioreticular cells. Type VI epithelioreticular cells form a distinguishing feature of the thymus- thymic (Hassall) corpuscles
- Blood-thymus barrier protects developing lymphocytes from exposure to antigens, consists of the endothelium and basement membrane of the continuous capillary wall surrounded by perivascular connective tissue with macrophages surrounded by a layer of epithelioreticular cells and basal lamina.

Spleen

The spleen is the largest lymphatic organ. It is located in the upper left quadrant of the abdomen, posterior to the stomach. It has a rich blood supply that is filtered through a reticular meshwork filled with macrophages and DCs.

Structure:
- Capsule of dense connective tissue with trabeculae that extend from into the parenchyma, contains myofibroblasts (contract to help discharge RBCs)
- Hilum– medial convex surface that contains location of passage for the splenic artery and vein, nerves, and lymphatics
- Red Pulp– contains large number of RBCs consisting of splenic sinuses separated by splenic cords. Cells here include reticular cells, RBCs, platelets, macrophages (remove damaged RBCs), monocytes, lymphocytes, DCs, plasma cells, and granulocytes.
- White Pulp– regions of lymphocytes surrounding an artery, appears basophilic . You will see a central artery surrounding by a periarterial lymphatic sheath (PALS), which resembles a lymphatic nodule.

Summary of lymph tissue:

Figure 14.4. Histology: A Text and Atlas: With Correlated Cell and Molecular Biology, 8e, 2020. Copyright © Wolters Kluwer

Lymph Tissue Slides

Oklahoma State University 44. Lymph Nodes, H&E. There are 8 annotation boxes, use this slide for the lymphatic system lab (med and grad students).
Use this link for the Blood Cell and Spleen Lab to practice identifying vessels (med students) there are 4 annotation boxes. Just focus on vessels for now, you will identify the other structures in a future lab.

This specimen slide contains 2 lymph nodes and neurovasculature bundles (A- artery, V- vein, N- nerves) leading to the hilum of each node. The neurovasculature bundles were not scanned in focus so they will look blurry as you zoom in, just focus on the lymph nodes. Lymph nodes are capsulated with a superficial cortex containing lymph nodules with germinal centers, a deep cortex where you can find High Endothelial Venules (HEV), and a medulla where cells are arranged in medullary cords surrounded by medullary sinuses. Deep to the capsule is a thin space known as the subcapsular sinus where lymph travels from the afferent lymph vessels and then into the cortex through the trabecular sinuses alongside the trabeculae. In the lymph nodules found in the superficial cortex, you’ll see central regions known as germinal centers where B lymphocytes are differentiating into plasma cells. The deep cortex lacks lymph nodules but contains T lymphocytes and HEVs where some lymph cells are entering the node. Notice HEVs look similar to other vessels but have thicker endothelial cells, not quite cuboidal but thicker than a typical squamous cell. Lymph will flow through medullary sinuses before exiting via efferent lymphatic vessels at the hilum.

GWU 021. Thymus, H&E. There are 3 annotation boxes.

The thymus is a bilobed, lobulated organ consisting of a darkly stained cortex and lighter stained inner medulla. T lymphocytes appear as small, dark, basophilic cells. Epithelioreticular cells are larger cells with oval nuclei and lightly stained cytoplasm. Macrophages are larger than epithelioreticular cells and also have a lightly stained nucleus but the cytoplasm and nucleus appear as irregularly-shaped. A distinct feature of the thymus is the presence of the thymic (Hassal) corpuscles which appear as tightly packed, concentrically arranged Type VI epithelioreticular cells.

GWU 023. Palatine tonsil, H&E. There are 4 annotation boxes.

Right and left palatine tonsils can be found on either side of the root of the tongue between the palatoglossal and palatopharyngeal arches. These are essentially collections of lymphoid nodules spread among cryptic infoldings which are lined by stratified squamous unkeratinized epithelium (also found throughout the oral cavity). The presence of this epithelium helps distinguish the palatine tonsils from the pharyngeal tonsils (found in “More Practice”) which are lined by pseudostratified ciliated epithelium with goblet cells (respiratory epithelium). Tonsillar crypts can be seen as open spaces in the tissue.

GWU 24. Spleen, H&E. There are 4 annotation boxes.

This specimen slide contains a portion of the spleen. Look for the dense connective tissue capsule covered by a layer of mesothelial cells. The mesothelial cells are found on abdominal organs that are covered by visceral peritoneum. This is a delicate layer that is difficult to maintain in fixed tissue. Trabeculae extend from the capsule into the parenchyma. When you examine the parenchyma of the organ, you’ll see mainly pink-red areas known as red pulp because of the large number of RBCs. you will notice collections of lymph cells that create blue-purple patches, this is the white pulp. You will also see central arteries and germinal centers surrounded by lymph cells (dark blue-purple), known as PALS. As the splenic artery enters the spleen, it divides into trabecular arteries that travel through the trabeculae to the white pulp where they are seen as central arteries. Trabecular veins drain the red pulp and travel through the trabeculae to join as the splenic vein leaving the spleen. RBCs that are aged and damaged are removed from the sinusoids and recycled.

GWU 79. Gastroesophageal Junction, H&E. There are 4 annotation boxes.

This specimen slide contains the junction of the esophagus and the stomach. Throughout the gastrointestinal track, you will find scattered lymph cells, small aggregates of lymph cells and lymph nodules. In the lamina propria, you can find lymphocytes and plasma cells. There is a large lymph nodule in the gastric mucosa that extends into the submucosa and contains a germinal center.

Michigan 28-1. Lymph node, Silver stain. There are 6 annotation boxes.

This specimen came from mesentery which suspends the small intestines from the posterior abdominal wall. There are multiple lymph nodes surrounded by adipose tissue, vessels (blood and lymph) and nerves. The silver stain was used to be able to see the reticular fibers, all of the black, squiggly lines. Use this specimen to identify the different lymph nodes and their features.

More Practice

Iowa Lymph Node. There are 5 annotation boxes.

Use this specimen to review structures of the lymph node.

GWU 049. Pharyngeal Tonsil, H&E. There are 2 annotation boxes.

Use this specimen to review structures of the tonsil, also pay attention to the epithelium in comparison to the palatine tonsil in the section above.

GWU 53. Ileum, H&E. There are 2 annotation boxes.

The ileum is another part of the small intestines but in this case, there are many lymph nodules in the submucosa known as Peyer patches which is specific to this organ. Other organs of the GI track contain aggregates of lymph cells while the ileum has structured lymph nodules.

Michigan 147B. Spleen, H&E. There are 3 annotation boxes.

Use this specimen to review structures of the spleen.

Michigan 141. Adult Thymus, H&E. There are 2 annotation boxes.

This specimen is an adult thymus. Compared to the specimen in the previous section, there is a lot more adipose tissue which slowly replaces the lymph cells over time starting around puberty.