Lymphatic System Histology PDF

LYMPHATIC SYSTEM HISTOLOGY Lymphatic System consists of: A. Cells 1. Lymphocytes (B,T, natural killer) 2. Antigen-presenting cells (dendritic cells, Langerhans’ cells & macrophages) B. Lymphatic “tissue” –diffuse and nodular C. Lymphatic “organs” (lymph nodes, spleen, thymus) D. Lymphati...

LYMPHATIC SYSTEM HISTOLOGY Lymphatic System consists of: A. Cells 1. Lymphocytes (B,T, natural killer) 2. Antigen-presenting cells (dendritic cells, Langerhans’ cells & macrophages) B. Lymphatic “tissue” –diffuse and nodular C. Lymphatic “organs” (lymph nodes, spleen, thymus) D. Lymphatic vessels that carry the cells and fluid  Lymphoid organs are classified as: Primary lymphoid organs Thymus Bone marrow Lymphatic nodules of the distal intestinal tract (e.g. ileum and appendix) Secondary (effector) lymphoid organs/tissue Spleen & lymph nodes (organs) Mucosal associated lymphoid tissue (MALT), e.g. lymphocytes and lymphatic nodules in the lamina propria Ross, Fig. 14.1 Primary Lymphoid Organs: The bone marrow and the thymus and the Gut-Associated Lymphoid Tissue (e.g. appendix, terminal ileum) are the initial “education centers” of the immune system In these organs, lymphocytes (T cells in the thymus, B cells in bone marrow and gut) differentiate into immunocompetent cells (i.e. they can recognize “self” vs. “nonself”) This differentiation is said to be antigen-independent The lymphocytes then enter the blood and lymph to populate: epidermis and mucosae connective tissue secondary lymphoid organs Secondary Lymphoid Organs: The lymph nodes, lymphatic nodules, tonsils, spleen are the secondary “education centers” of the immune system In these organs, immunocompetent lymphocytes differentiate into immune effector and memory cells that undergo antigen- dependent activation and proliferation in these organs. These lymphocytes then carry out their functions in the: connective tissue secondary lymphoid organs mucosal surfaces lining epithelia They participate in: Cell mediated immunity (mostly “cytotoxic” T cells) Humoral responses (production of antibody) (B cells, also requires “helper” T cells.  Lymph Nodes Main functions: 1. Filter lymph, thereby promoting lymphocyte contact with antigen 2. Provides necessary microenvironment for antigen-dependent differentiation Ross, Fig. 14.1 Schematic of Lymph Node Section of Lymph Node stain (H&E) 7  Lymphatic Circulation Through a Lymph Node Lymph nodes filter lymph 1. Afferent lymphatic vessels drain lymph into the Subcapsular Sinus 2. Lymph then passes to the Trabecular sinuses 3. From there, the lymph goes to the Medullary sinuses. 4. Lymphocytes and macrophages pass easily between these sinuses and the tissue of the lymph node. 5. Macrophages in sinuses monitor the fluids. Macs phagocytose the antigenic material and present it to T- and B-cells  Lymph Node Structure - Capsule & subcapsular sinus - Trabeculae & trabecular sinuses sinuses contain lymph, macrophages, and reticular cells - Cortex: superficial cortex (B-cells) -primary follicles/nodules -secondary follicles/nodules (i.e. with germinal centers) “deep” cortex (T-cells, dendritic cells) - Medulla: medullary cords (B-cells, plasma cells) medullary sinuses (lymph, more macrophages, plasma cells, and reticular cells) U-M Histology Collection High magnification view of a sinus (subcapsular sinus shown here) U-M Histology Collection M=macrophage, Ly=lymphocytes, RF/RC=reticular fiber (and associated reticular cell)  Reticular (Reticulin) Fibers Form a delicate supporting framework for highly cellular tissues (endocrine glands, lymph nodes, liver, bone marrow, spleen, smooth muscle). Composed mainly of Type III collagen, with a carbohydrate moiety that reduces Ag+ to metallic sliver = argyrophilic. Special stain: silver impregnation to visualize. Thinner than type I collagen (Type III fibrils are 30-40 nm diameter; type I fibrils are ~200 nm diameter) Source Undetermined  Lymphocytes in peripheral blood smear lymphocyte Mizobuti histology slide set These are B and T-cells that have undergone antigen-INDEPENDENT differentiation and are trafficking through the bloodstream on their way to lymphoid organs/tissue. Diapedesis: it’s not just for the Normans and the Saxons… Cytokines and chemokines (along with selectins and integrins) mediate EXTRAvasation of lymphocytes into tissues. Tether Roll Arrest Migrate blood flow cytokines chemokines L. Stoolman APCs and other cells Tonsils: MALT of the oropharynx United States Federal Government  TONSILS Ross and Pawlina, Histology: A Text and Atlas The palatine tonsils are paired structures made of dense accumulations of lymphatic tissue located in the mucous membrane of the junction of the oropharynx and oral cavity. The tonsils dip down into the underlying CT, forming crypts. There are also lingual tonsils and pharyngeal tonsils (under the roof of the nasopharynx and around the opening of the Eustachian tubes). Key features: crypts, abundant nodules, stratified squamous epithelium  Tonsils Simplest lymphoid organs Four groups of tonsils – Palatine, lingual, pharyngeal and tubal tonsils Arranged in a ring to gather and remove pathogens Underlying lamina propria consists of MALT PALATINE TONSIL  LYMPHOCYTES IN CONNECTIVE TISSUE: MALT = mucosa-associated lymphoid tissue LN Ross and Pawlina, Histology: A Text and Atlas U-M Histology Collection Diffuse lymphoid tissue Primary lymphatic nodule/follicle (LN) Lamina propria (LP) of gut shown here, but can be Aggregation of lymphocytes in lamina propria or found associated with mucosae anywhere in the submucosa gut, respiratory, and genitourinary tracts.  Secondary follicles/nodules Contain germinal centers Arise when B-lymphocytes are presented with appropriate antigen, receive T-cell help, and then begin proliferating as lymphoblasts Lymphoblasts differentiate into plasma cells or memory cells; aberrant lymphoblasts undergo apoptosis. Ross and Pawlina, Histology: A Text and Atlas  Microfold, or “M” CELLS Modified intestinal epithelial cells that assist in antigen presentation by conveying macromolecules from the intestinal lumen to underlying compartments housing lymphocytes and macrophages. Source Undetermined  M cells: TEM Source Undetermined After antigen presentation and T-cell help, activated B-cells set up germinal centers in secondary follicles Secondary follicle germinal centers Arise when B-lymphocytes are presented with appropriate antigen, receive T-cell help, and then begin proliferating as lymphoblasts Lymphoblasts differentiate into plasma cells or memory cells; aberrant lymphoblasts undergo apoptosis. Ross and Pawlina, Histology: A Text and Atlas Germinal center: high magnification U-M Histology Collection. Slide 175.  So, associated with just about any mucosa (GI, respiratory, genitourinary), you may see: Intraepithelial lymphocytes (T-cells) Diffuse lymphoid tissue: – B-cells – T-cells – APCs Primary nodules Secondary nodules – Germinal center with lymphoblasts and mphages Source Undetermined Regions of extensive lymphoid infiltration: Peyer’s patches Aggregates of lymphoid follicles in the ileum. Source Undetermined  Appendix Blind sac extending from the caecum primary and secondary follicles in lamina propria and submucosa So, clearly a secondary lymphoid organ… However, also a site of antigen-INDEPENDENT differentiation (similar to Bursa of Fabriscus is birds) So, also a primary lymphoid organ Sorry about the various “primary” and “secondary” nomenclature; that’s just the way it is… Aggregated Lymphoid Nodules And Appendix MALT – abundant in walls of intestines Fight invading bacteria Generate a wide variety of memory lymphocytes – Aggregated lymphoid nodules (Peyer’s patches) Located in the distal part of the small intestine – Appendix – tubular offshoot of the cecum  The Spleen Filters the blood Destroys old red blood cells Serves as an immune organ Divided into Red Pulp (RBC/ hemoglobin recycling) White Pulp (responsible for immune functions) Ross, Fig. 14.1 Spleen: Gross Anatomy Figure 14-27. Spleen 31  SPLENIC CIRCULATION Sinuses drain into splenic pulp veins, which, in turn, drain into trabecular veins. Trabecular veins travel within trabeculae and drain into splenic vein at the hilus. red pulp white pulp U-M Histology Collection  PALS w/ secondary follicle Shown here with “central” artery cut in cross section –note that the CA has been pushed off to the side by the rapid expansion of cells in the germinal center (GC) RP= red pulp MZ= marginal zone (antigen presentation) dashed circle = T-cell rich zone Ross, plate 35-3 WHITE PULP  White pulp function Blood and antigens pour into red pulp (more on that later) Antigen presentation takes place in MARGINAL ZONE T-cells (from PALS) provide “help” to activate mphages and B-cells activated mphages stimulated to destroy ingested material (e.g. bacteria) activated B-cells set up proliferative germinal centers U-M Histology Collection  Scanning EM of a Splenic Sinus (SS) and Cord of Billroth The cords contain, RBCs, neutrophils (N), macrophages (M), blood platelets (P) A reticular cell framework (RC) supports the cord. The sinus is bounded by the epithelial cells that form the basket-like structure of the sinus (VS) Ross 14.30a Spleen (red pulp) at high power (40x) sinus cord cord sinus U-M Histology Collection  Percolation of blood into splenic sinuses Here, you are inside the sinus looking through to the cord, where both a macrophage (M) and a neutrophil (N) are outside the sinus. Note that the endothelial cells have a rodlike appearance. Ross and Pawlina, Histology: A Text and Atlas; Source Undetermined Schematic of Spleen 39 The Spleen – Vascular Schematic  Splenic Circulation 1. Blood enters via splenic artery at hilus 2. Splenic artery branches into trabecular arteries (which travel within connective tissue trabeculae). 3. Trabecular arteries give off branches known as central arteries which leave the trabecula and enter the substance of the spleen (covered by a peri-arterial lymphatic sheath). 4. Central arteries branch into penicillar arterioles that piece through the lymphatic sheath and spill into splenic cords. 5. Blood percolates through splenic cords and across walls of splenic sinuses. 6. Splenic sinuses drain into pulp veins. 7. Pulp veins drain into trabecular veins. 8. Trabecular veins drain into splenic vein at the hilus.  The Thymus T-cell education Self vs. nonself distinctions Cell-mediated immune functions Populates effector organs Lymph nodes Lymphatic nodules Spleen Tonsils Ross, Fig. 14.1 THYMUS The Thymus is a Primary Lymphoid (Immune) Organ Responsible For the Education of T-Cells Located over the great vessels of the heart in the area of the body called the mediastinum Develops from an invagination of EPITHELIUM of the 3rd pharyngeal pouch, so an endodermal organ. Specialized epithelial cells (called epithioreticular cells) that are joined to one another by long processes with desmosomes on the extremities of the cells (like starfish joined together at the tips) make up the bag-like support for: Lymphocytes that, when the organ is young, fill this “bag”. NOTE: There are generally no B cells in the Thymus.  The Young Thymus Surrounded by a CT capsule; cortex has a lot of lymphocytes, fewer in the medulla THERE ARE NO GERMINAL CENTERS IN THE THYMUS! Gray’s Anatomy Ross and Pawlina, Histology: A Text and Atlas Source Undetermined  The Thymus undergoes a process called THYMIC INVOLUTION, as T cells leave the thymus to populate other lymphoid effector organs, the organ shrinks, leaving only the epithelioretucular cells U-M Histology Collection The young thymus Thymus at puberty U-M Histology Collection  Hassall’s corpuscles Type VI ERCs; function not very well known, but produce interleukins (such as IL-4 and IL-7) and so likely influence T-cell differentiation Source Undetermined Overview of T-cell “education” 1. Naïve T-cells enter medulla via diapedesis across venules 2. Pass into cortex to undergo POSITIVE selection: Presented with MHC molecules and self or non-self antigens by ERCs T-cells that recognize MHCs and self/non- self antigens “pass” this selection process and survive (those that don’t undergo apoptosis) 3. Move into medulla to undergo NEGATIVE selection: T-cells that recognize SELF antigens displayed by self MHCs (i.e. are :autoreactive”) are eliminated 4. Differentiate into helper (CD4+) or cytotoxic (CD8+) T-cells and leave medulla via diapedesis across venules  Blood-Thymus Barrier Education of T-cells must occur in a very controlled environment such that antigens are ONLY presented by epithelial reticular cells. To ensure that no other cells or free antigens are present, there is a very tight BLOOD-THYMUS BARRIER consisting of: 1. The blood capillary wall endothelial cells endothelial cell basal laminae pericytes 2. Perivascular connective tissue type III collagen macrophages 3. Epithelioreticular cell layer basal lamina of the epithelial reticular cells (type I ERCs) epithelial reticular cells (NOTE: T-cells can enter thymus ONLY via bloodstream – NO AFFERENT LYMPH VESSELS!)  Macrophage Source Undetermined Source Undetermined Source Undetermined  High mag view of medulla Source Undetermined T-cells that survive selection process allowed to cross venule endothelium (INTRAvasation) to enter circulation. Source Undetermined Role of Lymph Vessels in Metastasis - blind ended vessels - permeable to proteins even cells connection to the veins Elephantiasis – blockage by parasitic worms