20110126 07 lymphoid organs notes

From Iusmhistology

  • started here on 01/26/11 at 2PM.

Contents

[edit] Lymphoid organs

  • Accent is from Argentina, not Arkansas
    • Stop her with questions
  • She was an immunologist, so she has a hard time not mentioning the immunology part of these tissues.
  • Definition of lymphoid tissue: connective tissue enriched in lymphocytes.

[edit] Lecture objectives

  • Enumerate the types of lymphoid organs
  • Compare and contrast the histological characteristics of diffuse and nodular lymphoid tissues
  • Describe the localization and the cell types that compose diffuse lymphoid tissue
  • Describe the histological organization of the primary lymphoid organs
    • Bone marrow (covered in the blood cells lecture)
    • Thymus
  • Describe the histological organization of secondary lymphoid organs
    • MALT (mucosa associated lymphoid tissue):
      • Peyer's patches
      • tonsils
    • encapsulated lymphoid organs:
      • Lymph nodes
      • Spleen


  • We will not test over the immunology subject matter covered on pages 226-232 in your textbook (Basic Histology, 12th edition).

[edit] Organs

  • Organs can be classified as primary or secondary
  • Primary:
    • Where lymphocytes mature
    • Where they undergo antigen-indpendent maturation
    • Bone marrow
      • Where lymphocyte (NK, neuts, and T / B cell) precursors are generated
      • More on Monday
    • Thymus
      • Where T cytes mature
  • Secondary:
    • Lymphocytes become activated
    • Undergo antigen-dependent activation / maturation
    • MALT
    • Lymph nodes
    • Spleen


  • Organs can also be classified by their organization of the cells:
    • If lymphycotes are not organized the tissue is called diffused
    • Organized, round, masses called nodules or follicles characterize a tissue as being nodular.
      • These nodules are mainly composed of B lymphocytes

[edit] Connective tissue in lymphoid organs

  • Lymphoid tissue has particular cells and fibers to support lyphocytes
  • Reticular fibers:
    • See Bidwell's lecture.
    • Type 3 collagen
    • Dtermine mobility of cells int he tissue
    • Cannot be seen in H&E; require silver staining
    • Can be more or less packed; less or more mobility
    • Can form trabiculae

[edit] Cell type localization in lymphoid organs

  • No organization or localization in diffuse type tissue.
  • Diffuse lymphoid tissue is generally associated with mucous membranes
  • Nodular lymphoid tissue:
    • Have nodules that form organization
    • Some have centers that stain lighter; called germinal center
    • Here the cells are activated and are actively dividing and thus have more cytoplasm and a lighter stain.
    • Germinal centers are found in activated lymphoid nodules
    • This is generation of plasma cells going on here.
    • The nodules disappear after immune response is downgraded.

[edit] Three cell types make up diffuse lymphoid tissues

  • Dendritic cells:
    • Most potent APCs
    • Engulf antigen, process in cyto, present on membrane
    • Derived from bone marrow
    • Stain red with blue nucleus
    • They have dendrites (projections) to increase the SA that is exposed to the ECF so they can interact with lymphocytes
  • Lymphocytes:
    • B or T cells or NK
    • Effectors of immune response
    • We cannot tell the diff between B and T cells with LM or EM, must use specific antibodies agains surface prteoins.
      • Can tell the difference once they are activated.
    • B cells become plasma cells
      • Have clock-face nucleus
      • Have machinery to produce lots of protein
    • T cells
  • Plasma cells:
    • Make IgA
      • Can dimer
      • Has a secretory piece so it can be secreted to gut and milk
    • Activated B lymphocytes

[edit] Describe the histological organization of the primary lymphoid organs

  • We will talk about bone marrow on monday.

[edit] Thymus

  • Bilateral organ situated in the mediastinum.
  • Location of T lymphocyte maturation.
  • The thymus is active birth - puberty.
  • After puberty, fat replaces the thymus.
  • It has a particular structure with a cortex and medulla:
    • It is surrounded by a connective tissue capsule.
    • The capsule penetrates the parenchyma and divides it into incomplete lobules, each one with a cortex and a medulla.
    • The capsule sends projections into the parachyma called trabeculae to form the lobules.
    • The cells around the outside are the cortex and the cells in the middle are the medulla.
  • The cortex contains immature T lymphocytes, macrophages, and stromal epithelial reticular cells.
    • Here we can see that there's a fair bit of cytoplasm in the reticular cells.
    • The reticular cells produce factors that help the lymphocytes mature and also provid physical support.
  • The medulla contains differentiated (mature) T lymphocytes, epithelial reticular cells, and reticular fibrocytes.
    • There are hallmark structures of the medulla formed by cellular debris and reticular cells called Hassall's corpuscles or ? corpuscles.
      • These have no known function.
      • Hassall's corpuscles consist of epithelial reticular cells in concentric circles with keratin filaments filling the cells.
[edit] Activity of the cortex and medulla
  • The cells in the cortex, T cells undergo diff, maturation, and selection.
    • Only the T cells that recognize the MHC survive.
  • In the medulla there is negative selection
    • T cells undergo apoptosis if they bind too strongly to the MHC.


  • The cortex is isolated from circulation which is important so that T cells don't get away before they have been selected.
  • There are three structures that generate this Thymocyte-Blood barrier:
    • Continuous capillaries with tight junctions and a basal lamina; this keeps T cells from moving away aberantly.
    • Reticularcytes (type I) that are bound to one another with desomsomes to help stop
    • Perivascular connective tissue occupied by macrphages


  • Mature T lymphocytes have moved through the cortex, into the medulla and can then escape into the blood via venules at the corticomedullary junction.
  • There is no clear separation between the cortex and medulla; there is the cortico-medullar junction.
    • This region has blood vessels (post-capillary venules), AKA high endothelial capillaries.
    • These are lined by taller-than-usual endothelial cells and are the location where T cell exit the thymus.
  • The boy in the bubble
    • SCID pt, no B cell, T cell, or NK
    • Mutation in the gamma chain of some receptor.
    • Had a suit that he could use, too, to roam the world.
    • He got a bone marrow transplant.
    • Then got lymphoma becaue of CMV in the donor marrow.
      • First connectinon between CMV and cancer.
    • The thymus of patients with SCIDs is hypoblastic.
      • Smaller than it should be.
      • There is no epithelial cells in SCID thymus like there should be in the cortex.

[edit] Describe the histological organization of secondary lymphoid organs

  • There are two types of secondary lymphoid organs: mucus-associated and encapsulated.

[edit] MALT organziation

  • Stands for mucosa-associated lymphoid tissue
    • These tissues are found in the GI tract, the respiratory tract, and the GU tract.
    • These tissues have both diffuse' lymphoid organization and a non-encapsulated or partially encapsulated aggregation.
  • These are peyer's patches and tonsils and BALT
    • Sometimes we call MALT tissue BALT or GALT because it is in the bronchial tissue or gastrointestinal tissue.


  • Peyer's patches:
    • Peyer's patches are non-encapsulated.
    • They are large clusters of lymphoid follicles
    • They are found in the ilium of the small intestine
    • They are localized to the lamina propria and the submucosa
    • They often produce a bulge into the gut.
    • There are specialized M cells in the epithelium that covers the follicle.
    • The M cells help transport antigens and microorganisms from the lumen to the APCs and lymphocytes of the peyer's patch.
      • M cells present antigen to lymphocytes.
    • M cells don't have brush borders.
    • M cells have a little pocket below them, away from the lumen.


  • Tonsils:
    • Tonsils are considered partially encapsulated
      • The capsule is only found on the side that faces the oral cavity.
      • This is useful for keeping microorganisms out.
    • This lymphoid tissue lies just below and in contact with the epithelium of the oral cavity
    • There are three sets of tonsils:
      • Palatine tonsils, pharyngeal tonsils, and lingual tonsils.
    • Tonsils contain numerous lymphoid follicles with germinal centers.
      • Recall: dividing cells, more cytoplasm, stain lighter
    • Sometimes the lymphocyte proliferation is so large that we cannot see the epithelium.
    • Look for crypts

[edit] Encapsulated lymphoid organ organization

  • These are lymph nodes and the spleen
  • The lymph nodes and spleen are encapsulated and organized.
  • They contain immature and mature lymphocytes as well as accessory cells that surround.
  • There is connective tissue forming a capsule around the organs.
  • The arteries and veins of encapsulated organs pass through the hillum.
[edit] Lymph nodes
  • The lymph nodes are bean shaped.
  • They are found througout the body along the course of the lymphatic vessels.
  • Lymph nodes contain lymphocytes, macrophages, and other APCs (like dendritic cells and B cells), as well as reticulocytes.
  • The capsule is made of reticular fibers and sends of trabeculae that run into the bean shaped lymph node to form three distinct locations: cortex, medulla, paracortex.
  • Cortex:
    • Situated just under the capsule
    • The cortex has reticular cells, macrophages, APCs, and lymphocytes
    • The cortex also has lymphoid nodules with or without germinal centers.
    • Germinal centers are found when antigen has been presented and B cell proliferation and activation are underway.
    • There are subcapsular sinuses just below the capsule; these are formed by a reticular fiber mesh.
    • The cortical sinuses run between the lymphoid nodules and communicate with the subcapsular sinuses.
  • Medulla:
    • There are two structures to the medulla of the lymph node: medullary cords and medullary sinuses
    • The medullary cords contain mostly B cells, plasma cells, and macrophages.
    • The sinuses contain lymph, lymphoctyes, and macrophages.
  • Paracortex
    • The paracortex does not have precise boundaries
    • The paracortex will lack B cells yet accumulate T cells.
    • There will be postcapillary venules (high endothelial cappillaries) at the paracortical zone.
    • These postcapillary venules will have exceptionally tall endothelial cells.


  • Antigens and cells enter the lymph node through the afferent lymphatics and drain into the subcapsular sinuses and then into the cortical sinuses.
  • The cells and antigens that have entered the cortical sinus can either leave the node completely via the efferent vessels or can enter the cortex proper to a B cell zone or T cell zone.
    • At the B and T cell zones the cells can be activated.
  • Efferent lymphatics contain:
    • Activated B and T cells
    • Abs
    • Plasma cells
[edit] Spleen
  • The spleen is the second type of encapsulated secondary lymphoid tissue.
    • The first was the lymph node.
  • The spleen is a non-essential organ so one can live without it.
  • The spleen is the largest accumulation of lymphoid tissue.
  • The spleen is involved in filtration of blood, destruction of old erythrocytes, and production of antibodies and activated lymphocytes.
  • The spleen has a capsule that is formed by a dense connective tissue, just like the lymph node.
  • Again, as with the lymph node, the capsule has trabeculae that come off the capsule to divide it into separate compartments.
    • These trabeculae divide the parenchyma of the spleen (also called the splenic pulp).
  • The splenic pulp has pretty much everything in it: B and T cells, APCs, macrophages, and reticular cells.
    • It is considered a reticular tissue.
  • There are two components of pulp, named based on their color of fresh sections: white pulp and red pulp.
  • White pulp:
    • Looks bluish in staining
    • Has nodules.
    • Has periarteriolar lymphid sheaths (PALS)
      • These are blood vessels covered with T cells
    • Densely populated by T and B cells.
    • There are marginal sinuses around the lymph nodules; this is where antigens arrive from circulation and APCs present to lymphocytes.
  • Red pulp:
    • Red pulp is composed almost exclusively of splenic cords (cords of Bilroth) and venous sinusoids.
    • Sinusoids are spaces beween cords that contain blood cells.


[edit] =Blood flow in the spleen
  • This is a special type of circulation.
  • Blood enters the spleen through the splenic artery.
  • The splenic artery branches to form trabecular arteries which give rise to central arteries which follow the trabeculae.
  • The central arteries are surrounded by white pulp and the T cells within.
  • After traveling past the white pulp, the arteries split again into penicular vessels.
    • Now the blood is in the marginal sinuses of the white pulp.
  • Penicular vessels are a specialized set of vessels that carry blood into the red pulp.
  • Penicular vessels pass blood into sheathed capillaries.
    • Sheathed capillaries are surrounded by macrophages, not by endothelial cells. 
Does blood always go through sheathed caps or only in one of the two circulation options: open, closed?
  • At the red pulp, blood splits it's flow: closed circulation or open circulation.
  • Closed circulation:
    • This type of circulation is called closed because the blood is continuously bound by endothelial cells of the vessel walls.
    • In closed circulation, the penicullar arterioles and capillaries connect to the sinusoids.
    • In closed circulation, macrophages reach between the endothelial cells to detect and destroy old erythrocytes.
  • Open circulation:
    • Open circulation allows blood to flow into the stroma of the splenic cords.
    • The penicular arterioles are open-ended and thus let the blood flow directly into the splenic cords.
    • In the stroma, macrophages destroy aged / abnormal erythrocytes or any erythrocyitic chunks floating about.
      • Aged RBCs are targeted because their membrane is not flexible enough to let them get through the basement membrane of the sinusoids thorugh which they must pass if they want back into the circulation.
    • Intact RBCs leave the stroma via trabecular veins and the splenic vein.
  • In the white pulp, arterioles lead the blood to small sinuses that surround the PALS (periarterial lymphoid sheaths).
    • In the PALS, blood and APCs intermingle and antigens are trapped and presented to lymphoid cells.
[edit] Splenomegaly
  • Enlargement of the spleen.
  • Must look within the spleen to understand what is going on.
  • Can be diagnositic once you know what is accumulating within.

[edit] Lab prep

[edit] Appendix

  • Non inflammed
    • See the lamina propria
    • Submucosa
  • Enflammed
    • Epithelium is eliminated
    • Can see mitotically active lymphocytes
    • Can see germinal center
    • Can see how cells push epithelium into lumen
  • CT will be found below epithelium.

[edit] Tonsils

  • See the crypts

[edit] Lymph node

  • Find hillus by way of vessels
  • Find nodules
  • Find cortex and medulla
  • Find trabeculae
  • Find pericoritical zone

[edit] Spleen

  • Capsule, red and white pulp,
  • Find sinuses, cords
  • Lymphoid nodules

[edit] Thymus

  • Nodules, cortex, medulla
  • Cortex: Accumulation of lymphocyte precursors in cortex
  • Medulla: lymphocytes, hassel corpuscles.
    • Can see reticular cells, too

[edit] Cervix

  • Has columnar epithelium, etc.

[edit] Lab 8: Lymphoid tissue

Laboratory 8: Lymphoid Organs A. GUT ASSOCIATED LYMPHATIC TISSUE Lymphoid tissue occurs along the gastrointestinal tract as a diffuse infiltrate of leukocytes (primarily lymphocytes), as discrete foci or densly populated aggregates of cells (e.g. Peyer's patches in the ileum), and as organs (e.g. tonsils). Slide 59 appendix. There are two sections on this slide, taken from different regions of the same appendix. Start with the section that appears lighter in staining (contains fewer lymphocytes). Please take a moment to look ahead in your atlas and text to the chapters that describe the intestines. Use a diagram such as Fig. 15-2, 15-33, or 15-37 in Basic Histology to help defme layers of the gut wall. Loose connective tissue subjacent to the gut epithelium occupies a layer called the lamina propria, and is separated from a deeper region ofloose c.t. (i.e. the submucosa) by a narrow layer of smooth muscle (i.e. muscularis mucosa). The lamina propria typically contains many lymphocytes, and this is where you may fmd lymphoid nodules. Look at the other, more lymphocyte-rich section. How have lymphocytes altered the architecture of the organ? [For future reference, there are some excellent post-capillary venules associated with the lymphoid nodules in this section.] Peyer's Patch Slide 60 ileum Peyer' s patch. Peyer's patch is an extensive cluster of lymphoid nodules located in the wall of the ileum. Lymphocytes can so heavily populate the lamina propria that the epithelium appears to rest atop a dome. What is the position ofPeyer's patch relative to the mesentery (gross anatomical structure)? Tonsils Slide 27 palatine tonsil. Three sets of tonsils are located in the oral cavity and nasopharynx. We have a section of the palatine tonsil. The lingual tonsil and pharyngeal tonsil (adenoids) have similar histology. 34 11127/10 This slide (slide 27) can be very difficult to navigate, as fixation is poor and it is lightly stained. Make sure you look at an image of tonsil in your atlas (Basic Histology Fig. 14-15; Wheater 11.16). Use the scanning objective to locate the surface epithelium and intervening spaces called tonsilar crypts (epithelium-lined). The epithelium that lines the crypts tends to be indistinct due to heavy infiltration with lymphocytes. What is the orientation of lymphoid nodules and germinal centers to the tonsilar crypts (here "crypt" means lumen of a fold in the mucosa)? What type of lymphocyte occupies the nodule proper? What type of lymphocyte is found in intemodular areas? B. LYMPH NODE Slide 24 lymph node human. Slide 25 lymph node monkey. Lymph nodes are encapsulated lymphoid organs. They have a dense collagenous connective tissue capsule from which thin, collagenous trabeculae extend into the substance of the node. The point where vessels and efferent lymphatics are located is called the hilus. Afferent lymphatics can be seen in the capsule. The hilus is commonly indented (gives some nodes a kidney bean shape). Note, in some of these slides (slide 24) there is a sectioning artifact. Do not mistake this for the hilus. Lymph nodes have a cortex, a paracortical zone and a medulla. There are no abrupt/rigid boundaries between these regions. Instead, lymphoid nodules (some with germinal centers) predominate in the cortex. The paracortical zone is the area immediately deep to the cortex, and the medulla is innermost, a region made up primarily of lymphatic vascular channels and the irregular cords (medullary cords) of tissue that surrounds them. Look for mitotic lymphocytes in the germinal centers of the cortex. Which class of lymphocyte predominates in the lymph node cortex? Look deep to the nodules of the cortex to locate the paracortical zone. A definitive marker of the lymph node paracortex is the postcapillary venule (also called "high endothelial capillary"). These vessels are lined by extremely tall endothelial cells. Recall that PCV's can be found in other lymphoid organs as well (e.g. intemodular areas of tonsil, appendix), but they are fairly prominent here in the lymph node. What is the function of the postcapillary venule? What class of lymphocyte surrounds them? 35 11127/10 Lymph nodes function as in-line ftlters for the lymphatic vasculature. Afferent lymphatics join the node at its capsular surface, and efferent lymphatics leave the node at the hilus. Because lymphatics are so delicate it is rare to find a patent afferent channel crossing the capsule. Instead, you should see lymphatics running within the plane of the capsule. You can distinguish lymphatics from blood vessels by their contents. If the lumen contains RBC's it is not a lymphatic. There are three lymph sinuses in the path that leads from the capsule to the hilus. Lymph flows from afferent lymphatics in the capsule to the subcapsular (or cortical) sinus, to trabecular sinuses that run along collagenous trabeculae, to medullary sinuses which lead to the efferent lymphatics exiting at the hilus. Look for endothelial valves in the afferent and efferent lymphatics. These valves help minimize backflow in this very low pressure system. Lymphatics have little-to-no smooth muscle in their wall to regulate flow. In slide 24, medullary sinuses have an eosinophilic background contributed by cytoplasm of macrophages, fibroblasts and reticular fibrocytes. The medulla in this specimen is so heavily populated by lymphocytes that it may be difficult to see the lumen of medullary sinuses. The sinuses are flanked by densely-populated narrow cords of tissue (medullary cords). The cords are also heavily populated by lymphocytes, such that it is very difficult to see the fibroblasts and reticular fibrocytes that produce the fibrous framework of the node. Slide 22, which has far fewer lymphocytes, is stained with Wilder's reticular stain, and the reticular fibers stain black. Macrophages are an important cell type in lymph nodes. Slide 36 (leopard lymph node) contains clusters of active macrophages marked by yellow-brown intracellular debris. C. SPLEEN. Turn to the diagrams and photomicrographs of the spleen in your text and atlas. Study those references before you examine slide 26 and the demonstration slide of spleen. (Note: Don't miss seeing this demonstration slide. It is far superior to slide 26.) Slide 26 spleen. The spleen is an encapsulated lymphoid organ that plays an important role in immune response and the degradation of spent RBC's. Structure and function of the spleen is dominated 36 11127110 by the vasculature, and most of the structures we will emphasize are related to the pattern of blood flow through the organ. The largest arteries and veins follow collagenous trabeculae that extend inward from the capsule. These trabecular vessels (it is not necessary to distinguish between arteries and veins) should be easy to fmd. White Pulp: Arteries that branch from the trabeculae to enter the parenchyma of the spleen are surrounded by lymphoid tissue. This lymphoid tissue-rich region is called white pulp. Look at slide 26 with the inverted eyepiece. The white pulp appears blue (!), because it is heavily populated by lymphocytes. At higher magnification look for germinal centers (areas ofB-cell amplification). Textbooks describe narrow, thin-walled sinuses (i.e. marginal sinuses) at the periphery of germinal centers in the spleen. These are not readily visible in slide 26 (identification not required). To the side of (eccentric to) each germinal center locate a central arteriole (central artery of the white pulp). Lymphocytes (mostly T-cells) that surround central arteries populate the periarteriolar lymphatic sheath (PALS). Outside the PALS is the peripheral white pulp (PWP, mostly B-cells ). The boundary between the PALS and PWP is indistinct. Thus, white pulp structures include: central arterioles, periarteriolar lymphatic sheaths, peripheral white pulp, germinal centers, marginal sinuses (identification not required for marginal sinuses). Red Pulp: Small arterioles leave the white pulp and lead to capillaries that perfuse the surrounding, highly vascular red pulp. These arterioles and capillaries are not identifiable in this slide. The red pulp consists of vascular spaces (splenic sinuses) surrounded by tissue (splenic cords= cords ofBilroth). In slide 26 the spleen is engorged with RBC's, and against this background it is very difficult (but not totally impossible) to distinguish between the splenic sinuses and splenic cords. Spleen demonstration slide: We have a slide (in short supply) that shows red pulp structures much more clearly than slide 26. With this slide, identify the sinuses and cords. Look for the elongated endothelial cells that line the sinuses. There are wide gaps between these cells, and blood cells readily cross the wall to flow among the cells of the splenic cord. It is primarily within the splenic cords that macrophages destroy aged RBC's. Thus, red pulp structures include: arteries and capillaries of the red pulp (identification not required), splenic sinusoids, splenic cords. 37 11127/10 D. THYMUS. Slide 29 thymus human. Slide 29 is thymus from a neonate. Observe the arrangement of each lobule into a cortex and medulla. Are germinal centers present? Is a capsule present? The cells that form the stroma of the thymus are called epithelial reticular cells. They are easiest to see in the medulla and typically have large euchromatic nuclei surrounded by considerable cytoplasm. Identify Hassall's corpuscles. E. DIFFUSE, UNORGANIZED LYMPHOID TISSUE Slide 81 cervix human. You have already seen diffuse lymphoid tissue in the wall ofthe gut, where lymphocytes have migrated to sites of antigenic challenge. When the lymphocytes are present in relatively small numbers it is described as a diffuse infiltrate. When very large numbers of lymphocytes are present, the cells can either be unorganized or they can form discrete nodules or follicles that may contain germinal centers. Slide 81 of the cervix shows diffuse lymphoid tissue. Look for lymphocytes (there are some good plasma cells here as well) in the connective tissue beneath the epithelium, especially in the region where the vaginal epithelium (stratified squamous) joins the epithelium of the cervical canal (simple columnar). You can see the cervical canal (unaided eye) near the midline of the section. 38


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