01282013 - Lymphoid Organs

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Lymphoid tissue

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Tissue heavily populated with lymphocytes
- Primary lymphoid tissue = source of the cells - marrow, thymus
- Undergo antigen-independent differentiation
- Secondary - where lymphocytes migrate, and are activated
- Activation IS antigen dependent

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Primary lymphoid organs

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Bone marrow - site of B-cells, NK cells, dendritic cells, and T-cell precursors
- Thymus - maturation site of T-cells

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Secondary lymphoid organs

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- Lymph nodes, spleen, mucosa-associated lymphoid tissue (MALT)

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Lymphoid tissue structure types

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- Diffuse = accumulation of lymphocytes with no apparent organization
- Cervix - dark staining lymphocytes spread out everywhere
- Nodular = Lymphocytes arranged in spherical masses - containing mostly B-cells
- Spherical masses have darker outer, lighter staining inner

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Germinal center

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- Present in lymphoid nodules
- Contain actively dividing cells = have more cytoplasm = stain more lightly!
- Disappear after completion of immune response

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Reticular cells/fibers

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- Provide support to cells in most lymphoid tissue (except thymus)
- Reticular cells = type of fibroblast - produces collagen III for these fibers
- Density of fibers determines the mobility of the cells in tissue

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Diffuse lymphoid tissue

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- Associated with mucous membranes (digestive, respiratory, and urinary tracts)
- Near areas prone to infiltration by pathogens
- Not encapsulated, no real boundaries

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Diffuse lymphoid tissue cells

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- lymphocytes, dendritic cells, IgA-secreting plasma cells
- Dentritic cells = most potent APC!
- Lymphocytes = WBC's responsible for specificity of adaptive response
- B, T, or NK
- IgA-secreting plasma cells = derived from B-cells
- IgA has component that makes it resistant to enzymes (in gut, etc.)

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Thymus overview

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Bilateral organ located in mediastinum - encapsulated
- Maturation of T-cells here
- Max function at birth - gradually replaced by adipose tissue (white spaces)
- Has outer capsule, lobules that are segregated by trabeculae (walls)
- Parenchyma (lobules) - Cortex/cortical area at periphery = more densely stained
- Medulla (center) - lighter stain
- Cortex = Immature T-cells (thymocytes) and macrophages in stroma of reticular cells
- Reticular cells have large cytoplasm, prominant center nucleus
- Medulla = More spread out!
- Mature T-cells, epithelial reticular cells, reticular fibrocytes
- Hassal's corpuscles (function unknown)

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Thymus-blood barrier

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- In cortex, immature cells cannot distinguish "self" from exogenous particles
- Barrier keeps immature cells from seeing cells/antigens in the blood
- Cortex capillaries = continuous endothelial cells, tight junctions
- Basal lamina of cells surrounding capillaries - prevents leakage of proteins, etc.

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Post-capillary venules

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- Classic of cortex-medulla junction
- Provides avenue for mature T-cells to exit into circulation

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Severe combined immunodeficiency disease (SCID)

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- Severe defect in B-, T-, and NK cells

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Mucus associated lymphoid tissue (MALT) overview

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- General term for tissues in GI, respiratory, and genitourinary tracts
- Lymphocytes and supporting cells hang out in these areas
- Composed of diffuse lymphoid tissue and non- or only partially-encapsulated organized sections

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Bronchus-associated lymphoid tissue (BALT)

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- A type of MALT in the lungs

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Peyer's patches

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- Found at small intestine (5-25 of them) - accumulation of lymphoid tissue
- M-cells - no brush border = sense/pick up antigens from gut lumen, pass them inside to lymph cells
- Plasma cells receive antigens from B-cells, helper T-cells - release IgA
- IgA goes out to gut = neutralizes antigens!

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Tonsils

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- Partially encapsulated diffuse lymphoid tissue
- Only has CT capsule on side that faces other tissue - oral cavity side doesn't have capsule
- CT capsule limits the movement of bacteria into the bloodstream
- Have lymph nodules and other diffuse lymph cells present

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Lymph nodes

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- Bean-shaped structures distributed throughout body along lymphatic vessels
- Encapsulated by CT
- Parenchyma again divided into cortex, paracortex, medulla
- Paracortex = area of transition between cortex and medulla
- Capsule again has projections of trebeculae - segment the interior
- Afferent lymph vessel brings lymph
- Hilum = where artery, vein, and efferent vessels enter node
- Cortex = contains lymph nodules

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Lymph node cortex overview

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- Overall, ID by presence of lymphoid nodules (with/without germinal centers)
- Reticular cells, macrophages, antigen presenting cells, B-cells
- Lymphoid nodules with/without germinal centers
- Subcapsular sinuses - immediately beneath capsule - allow fluid to flow in from afferent vessels
- Have reticular fiber meshes
- Cortical sinuses - run between nodules and communicate with subcapsular sinuses

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Paracortex overview

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- Area of transition between cortex and medulla
- T-cells, but no B-cell nodules
- Post-capillary venules - reentry of mature cells into circulation
- lined by TALL endothelial cells

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Medulla overview

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- Medullary cords - contains B-cells, plasma cells, macrophages
- Look like solid islands surrounded by medullary sinuses
- Medullary sinuses - spaces containing lymph, lymphocytes, and macrophages
- Appear open and "empty" with some cells inside

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Lymph node circulation

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- Lymphocytes enter nodes via post-capillary venules - move to specific areas
- B-cells to cortex nodules, T-cells to medullary area
- Antigens, dendritic cells, other lymphocytes bearing antigens enter via afferent vessel
- B-cells activated, T-cells activated
- Lymphocytes exit via efferent vessels back into circulation to help response

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Spleen overview

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- Main function - filtration of blood, destruction of aged RBC's, produce antibodies and active lymphocytes
- Thick CT capsule
- Splenic Pulp - spleen parenchyma - has reticular cells, lymphocytes, macrophages, APC's
- Periarteriolar lymphoid sheathes (PALS) - lymphoid tissue lining arterioles = T-cells get antigens!
- White pulp = lymphoid nodules and PALS
- To ID - look for tissue staining blue/purple, has lymphoid nodules with offset arterioles
- Red pulp - Reticular tissue with reticular cells, lymphocytes, other blood cells, macrophages, and APC's
- similar to lymph nodes - have splenic cords (Cords of Gilroth), sinusoids
- Sinusoids smaller than nodes, contain blood in vivo

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Splenic circulation

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Splenic artery -> enters capsule -> branches all over into trebeculae = trebecular arteries
- Trebecular arteries branch - become surrounded by PALS (T-cells) = called central arteries
- Central artery runs through white pulp (lymphoid nodules) - small capillaries branching off supply periphery of nodules
- Penicillar arterioles - when central arteries exit white pulp, enter red pulp
- Closed circulation - when arterioles are surrounded by endothelium (and macrophages) -> capillaries -> trebecular veins
- Open cirulation - arterioles surrounded by macrophages transition to cords - blood cells run through cords
- Lymphocytes are flexible and platelets are small - easily pass through
- Young RBC's = still flexible, pass just fine
- Old RBC's (>120 days old) = less flexible, rupture, cleaned up by macrophages
- Cells move back through cords to sinusoids -> trebecular veins -> exit spleen into circulation

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Appendix inflamed vs. non-inflamed ID

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Normally, can see epithelial cell structure well
- Inflamed version = can't see any distinct cells/morphology - blended purple
- Inflamed also has lymphoid nodules present and a ton of lymphocytes in general

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Ileum Peyer's Patches ID

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- Diffuse tissue, so no capsule - but still see germinal centers (darker cortex, ligher medulla appearance)

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Tonsils ID

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- Semi-diffuse lymphoid nodules - have germinal centers, CT on one side with invagination

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Lymph node ID

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- Hilum is ID'd by seeing lymph vessels and blood vessels together
- Cortex has lymphoid nodules
- Medulla has cords, sinuses
- Trebeculae throughout extending from thin outer capsule
- Paracortex - found via high endothelial venules
- Lymph vessels - no RBCs, a few lymphocytes inside
- Lighter pink color than surrounding tissue
- Lymphatic valves - thin endothelium extentions into vessels

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Spleen ID

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- Outer capsule, trebeculae
- Red pulp - Cords and sinuses
- White pulp - nodules, central (offset) arterioles with PALS

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Thymus ID

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- Lobules with cortical, medullary regions
- Cortex - more dense, darkly staining
- Medulla - corpuscles present

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Cervix ID

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- Transitional area between squamous stratified epithelium -> columnar
- Diffused lymphocytes hanging out around there