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Lymphoid Tissues
- masses of lymphocytes + associated cells required to mount an immune response
- they provide an environment that promotes immune cell / antigen interaction (which varies depending on whether antigens are in the lymph, blood, oral cavity, etc.)
- they can exist as discrete organs (covered by an epithelium or CT capsule) OR they may exist as isolated masses of cells in various organs that are in close proximityto the outside world
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Common Themes in 4 Lymphoid Tissues
- all lymphoid tissues (regardless of location) have LOTS of lymphocytes
![Image Upload 2](/flashcards/images/image_placeholder.png) - lymphocytes have a very high nucleus to cytoplasmic ratio; can be packed close together
![Image Upload 4](/flashcards/images/image_placeholder.png) - as a result, most lymphoid tissues are basophilic (lots of them, & nucleus being negative, picks up the hematoxylin)
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How to Differentiate Lymphoid Tissue from Other Highly Cellular Tissues
![Image Upload 6](/flashcards/images/image_placeholder.png) ![Image Upload 8](/flashcards/images/image_placeholder.png) - can see all the tissues are very cellular with little CT
- can see that with cells per unit area (circles), there are many more with the thymus as opposed to liver/pituitary because cells are so small
- in the nuclei themselves there are more clear areas in liver/pituitary (representing euchromatin) - there’s not much of this in lymphocytes
- much MORE cytoplasm in liver/pituitary than in thymus (the pink cytoplasm in the thymus DOESN’T belong to lymphocytes)
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Lymphoid Tissues Develop in a 2-Step Process
- Bone Marrow + Thymus: primary lymphoid organs; give rise to immunocompetent B & T cells
- these cells exist primary & populate secondary lymphoid organs (eg. lymph nodes, spleen, mucosa-associated lymphoid tissues [MALTs])
![Image Upload 10](/flashcards/images/image_placeholder.png)
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Immunocompetent
responds to foreign antigens
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Development of Immunocompetence
- precursor cells will express lots & lots of receptors on their surface by chance (TCRs or membrane bound antibodies)
- these receptors are pretty much against ANYTHING
- the ones that have receptors that bind to self are destroyed
- remaining cells = immunocompetent, each cell is specific for 1 foreign antigen
![Image Upload 12](/flashcards/images/image_placeholder.png)
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Thymus
![Image Upload 14](/flashcards/images/image_placeholder.png) - is a very lobulated organ; can see CT septa ‘penetrating’ in, dividing it up into lobules
- each septa is jam-packed with lymphocytes (intense basophilic region in the cortex)
- medulla contains fewer lymphocytes (lighter central region) & is essentially continuous (incompletely lobulated)
- has CT capsule around the outside of the organ (penetrates in to create lobules)
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What are responsible for the Thymus’ starry-sky appearance?
- Macrophages = the clear ‘white’ star areas
![Image Upload 16](/flashcards/images/image_placeholder.png) - macrophages are quite big, displace all lymphocytes from the area, less basophilic (white)
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Thymus Development
- out-pocketing of epithelial cells from the developing pharynx migrate to the upper mediastinum where they form the cytoreticulum
- epithelioreticular cells make up the cytoreticulum - form long processes that connect with each other
![Image Upload 18](/flashcards/images/image_placeholder.png) - result is a net supporting the thymocytes (T-cell precursors)
- there are really no reticular fibers in the “substance” of the thymus
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Thymotaxin
- hormone released by epithelioreticular cells that recruits T cell precursors (immature thymocytes) FROM bone marrow to populate area between the cytoreticulum
- these cells can then mature to become immunocompetent
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Epithelioreticular Cells
- are epithelial so they’re cytokeratin positive
- they support the thymocytes (the thymus has no supporting reticular fibers)
- they contribute to the blood thymus barrier, preventing true foreign antigens from entering the thymus & being considered “self”
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- Epithelioreticular Cells
- aren’t very visible unless you stain for them specifically
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Hassall’s (Thymic) Corpuscles
![Image Upload 22](/flashcards/images/image_placeholder.png) - concentric layers of epithelioreticular cells found only in the thymic medulla that secrete thymic stromal lymphopoietin (TSLP)
- TSLP stimulates differentiation of regulatory T-cells
- the corpuscles PERSIST in an involuted thymus
![Image Upload 24](/flashcards/images/image_placeholder.png)
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Why are there so many macrophages in the developing Thymus?
- in the process of development as you become immunocompetent, the majority of thymocytes don’t make it through positive/negative selection
- a lot of cell death takes place
- macrophages clear the dead cells
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Unencapsulated Secondary Lymphoid Organs
- Tonsils (lingual, palatine, pharyngeal)
- Peyer’s Patch
- Appendix
- these can be distinguished by the type of epithelium that covers them
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From inside the lumen, working outward:
- the gut lumen is lined by epithelium → lamina propria → muscularis mucosa (may or may not be present) → submucosa
- MALT can be found anywhere in the above regions
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MALT (Mucosa Associated Lymphoid Tissue)
- a type of UNENCAPSULATED secondary lymphoid tissue
- 1. Peyer's Patches (gastrointestinal)
- 2. Appendix (gastrointestinal)
- 3. Tonsils (gastrointestinal & respiratory tract)
- (other unencapsulated types of secondary lymph tissue = Bronchus ALT, GutALT, SALT)
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MALT
- lymphoid tissue that isn't necessarily an organ can be anywhere pathogens can access the body
- just a clump of lymphocytes near a lumen should be a BALT or MALT indicator
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What 3 layers constitute a mucosa?
- epithelial lining
- lamina propria
- muscularis mucosa
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What do all Secondary Lymphoid Organs contain?
- Nodular & Diffuse lymphoid tissue
- Nodule (Germinal Center): circular areas made up of masses of B cells proliferating
- Diffuse: area in between germinal centers; are made up of mostly T-cells
- B cells in Nodules, T cells in Diffuse areas
![Image Upload 26](/flashcards/images/image_placeholder.png)
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How can a secondary lymphoid organ be easily distinguished?
by NODULES - if there are nodules, the organ is secondary
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Nodule
- contains germinal center (clearing or light-colored area) where B cell proliferation occurs
- have macrophages in these areas as well to clear dead differentiated B cells
- B cells die in the nodules because they lack the strongest affinity receptors
- once cells with the strongest receptors (Igs) to antigen are selected, they escape nodule, move to nearly CT (medullary cords), & ultimately differentiate into a plasma cell that secretes this high affinity antibody
![Image Upload 28](/flashcards/images/image_placeholder.png)
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Tonsils
- Palatine: 2 on either side in the oropharynx
- Pharyngeal: in nasopharynx
- Lingual: bunch on the back of the tongue
- all 3 are identical once you get deep to their epithelium, so what distinguishes them is their epithelial covering
- tonsils = unencapsulated secondary lymphoid organs
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Crypts
- found in any tonsil, extend down from the surface deep into the organ
- they vastly increase surface area so that any potential antigens in the oral cavity can be exposed to immune cells that exist just under the covering epithelium
- lymphocytes will often migrate into the epithelium & sample antigen at the surface
![Image Upload 30](/flashcards/images/image_placeholder.png)
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Palatine Tonsil
![Image Upload 32](/flashcards/images/image_placeholder.png) - looks like a little oval zoomed-out
- surrounded by a stratified squamous epithelium (SSNKE)
![Image Upload 34](/flashcards/images/image_placeholder.png)
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Pharyngeal Tonsil
![Image Upload 36](/flashcards/images/image_placeholder.png) - have a pseudostratified ciliated columnar epithelium with goblet cells; a ‘respiratory’ epithelium
![Image Upload 38](/flashcards/images/image_placeholder.png)
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Lingual Tonsil
also has a stratified squamous epithelium (SSNKE), so it’s indistinguishable from a Palatine Tonsil
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Peyer's Patch
- masses of lymphocytes mostly found in the ilium of the intestine
![Image Upload 40](/flashcards/images/image_placeholder.png) - can tell it’s mucosa-associated because the line running through the patches of lymphocytes = the muscularis mucosa
![Image Upload 42](/flashcards/images/image_placeholder.png) - can see nodules deep to the muscularis mucosa; nodules exist in the submucosa
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M Cells (Microfold Cells)
- cells that exist in the (simple columnar) epithelium overlying Peyer's patch nodules
- have a deep basal invagination that forms a pocket of immune cells so they can get as close to the gut lumen as possible
- via pinocytosis M cells take up intact pathogens so immune cells can make antibodies against them
- Igs are released into lumen to inactivate antigen (the basis of oral vaccination)
![Image Upload 44](/flashcards/images/image_placeholder.png)
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Appendix
- blind-ending sac coming off the 1st part of the ascending colon (cecum)
![Image Upload 46](/flashcards/images/image_placeholder.png) - contains a lumen lined by an epithelium (with no vili, characteristic of the colon, but does contain intestinal crypts)
![Image Upload 48](/flashcards/images/image_placeholder.png) - see nodules deep to columnar epithelium cells (tells us we’re in the gut)
- is abundant with M-cells
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