10.4 Lab + Lecture Notes Flashcards
Primary Lymphatic Organs
- Responsible for generation of immune system
- bone marrow
- thymus
Secondary Lymphatic Organs
- Sites where cells work
- different levels of organization ranging from simple (i.e. MALT) to medium (tonsils - modifications in tissues to allow lymphatic cells to work) to very organized (spleen, lymph nodes)
NK Cells
= natural killer cells (= lymphocytes - but not T-/B-cells have a different progenitor)
- detect down regulation of MHCI in somatic cells
- respond quickly (good for tumor detection) –> destroy or mark for destruction
- FXN: kill things that lack MHCI or express in lower than normal amount - in an antibody-independent manner
B-lymphocyte
main FXN = recognize foreign antigens and produce antibodies –> just tag invaders
- when recognize an invade, will be “activated” - rapidly undergo mitosis (in lymphoid follicles) - create army of B-cells to opsonize invader
Opsonization
= coat the invader (in antibodies)
= a simple signal to tell other cells to kill it
Antibodies what are the five major ones we discussed
- contain variable and constant regions
- IgG
- IgM
- IgA
- IgD
- IgE
IgG
= majro antibody of blood + lymph
- complement activation
- crosses placenta
IgM
= first antibody formed
- complement activation
- B-cell receptor
IgA
= major antibody of secretions
IgD
= membrane antibody only
IgE
= major antibody of allergic responses
- Fc portion binds to mast cells /basophils
T-cells what are the four types we discussed
- CD8 - Killer (cytotoxic) T-cells
- CD4 - Helper T-cells
- CD 4 regulatory (suppressor) t-cells
- Delta-gamma T-cells
Describe Killer (cytotoxic T-cells), include what CD protein and MHC complex are used by them
- CD8
- scan MHCI on somatic cells
- MHCI has two activities
1) constant = tell other cells it blend to body and avoid NK cell response
2) variable = cuts up currently transcribing protein and displays on MHC I variable region –> allows B-cells to recognize and mark the invader
Describe Helper T-cells, include what CD protein and MHC complex are used by them
- CD4
- scan MHC2 on APCs
Describe Suppressor T-cells
- regulatory T-cells
- FXN in regulating Adaptive Immune response
- CD4
Describe delta-gamma T cells
- see in tonsils
- contain variant TCR - not restricted to MHC
- TCRs are enriched in intraepithelial lymphocytes
Describe the 3 types of APCs and what cell do they activate
- 3 types that activate CD4+ “helper” T-cells
1) Dendritic Cells - including Langerhans Cells in skin
2) Macrophages - including tissue-specific macrophages –> are phagocytic and can activate CD4 system
3) B-cells - for its specific antigen
What are the six points of the immune response system roughly from least to most specific
1) Complement System
2) NK cells
3) Macrophages
4) B-cells and antibodies
5) Tc-cells, MHCI
6) Th-cells + APCs, MHC II
Describe the Thymus
- derived from endoderm
- ball of epithelial cells - retains that character but no lumen - has CT around it
- Cells = thymocytes + ERCs
- is one of two primary immune organs
- blood-thymus barrier - traps naive thymocytes in thymic cortex –> ERCs = barrier against reentering circulation or moving into medulla
What are the parenchymal cells of the thymus
= thymocytes = T-cells - all leave the marrow as CD4- and CD8-
- acquire immunocompetence by learning to recognize non-self molecules presented on MHCI and MHCII
- purple staining
What are the stromal cells of the thymus
- Epithelial reticular cells (ERCs)
- FXN to form a barrier in organ to prevent certain thymocytes that are self-reactive from entering efferent vasculature
- control, guide, lightly test the development of lymphocytes
- pink staining
Describe Thymic aging
- involution (just like in bone marrow)
- thyms is most active in child hood
- in its senescence its t-cell parenchyma is largely replaced by adipose tissue
Describe Thymic embryology
- derived from endoderm at level of 3rd pharyngeal arch
- induced to from by ectomesenchyme (neural crest cells)
Describe the circulation of the thymus
- Capillaries all ascend through the cortex then loop around to come back out
Describe the micro-environment and compartments of the thymic cortex + medulla
- ERCs guard the entrance to cortex/medullar
- ERCs create a perivarscular space (PVS) between them and medullary vessels
- to get into the cortex and out through the medulla need to pass from Endothelial cell –> CT compartment –> ERC (cortex) –> ERC(medulla/cortex barrier)–> ERC (medulla/endothelial cell) –> CT compartment –> Endothelial cells
Describe the positive and negative selection of thymocytes
- All thymocytes enter thymus as CD3-, CD4-, CD8-
- Positive selection occurs at the thymic cortex - thymocytes are all taught to express all three of the CDs
- Negative selection occurs at the corticomedullary border - have to prove dedication to either CD4 or CD8 (be + for 1 of the 2) to enter the medulla
- only immunocompetent cells are allowed access to PVS
Describe Hassall’s Corpuscles
- made of ERCs in particular conformation
- only exist in medulla of thymus
- identification of thymus by them
Describe the Secondary Lymphatic Organs
1) Muscosa-Associated Lymphatic Tissue(MALT); includes GALT, BALT (lymphoid follicles); payers patches (M-cells) appendix
2) Tonsils - system of 3 in a ring around the GI system - reticulated epithelium - 1)palatine 2) lingual 3) pharyngeal
3) lymph nodes
4) Spleen (white pulp, splenic macrophages, splenic follicles)
Tonsils
- tonsils of Waldeyer’s Ring = Pharyengeal tonsil, Palantine tonsil, lingual tonsil
- SSNK epithelium - discontinuous BM + deletion of a few desmosomes –> provides spaces for lymphocytes to invade and have access to lumenal contents (delta gamma lymphocytes)
- reticulated epithelium of palatine tonsil = cells of epithelium made into reticular networks -much like thymic ERCs –> see lymphocytes there because of the organized lymphatic tissue sitting underneath the tonsils
Lymphatic System
- lymph consists of = extracellualr interstitial fluid from CT; immune cells (mostly, lymphocytes); antigens; lipids; macromolecules
- Lymphatic vessels - originate in periphery + carry lymph from CT all over the body - through a system of lymph nodes back to venous CVS near heart
- Lymphatic vessels sprout embryologically from walls of veins
Lymph Node
- afferent lymphatic into node pierces through the CT capsule
- FXN is to allow contact between peripheral lymphocytes that have sen invaders can interact with naive lymphocytes of blood and recruit them
- most of lymphocytes occurring there are from circulation
- to exit node –> must cross back into lymphatic sinus and leave from medullar sinus through efferent lymphatics
Describe what is labeled by the following CD markers: CD10 CD20 CD3 CD45 CD5 BCL6 KI67
CD10 - Cells in the germinal Center of lymphoid follicles undergoing clonal expansion - Plasma cells
CD20 - B-cells and plasma cells (not T-cells)
BCL6 - Plasma cells
KI67 - Labels proliferation (Plasma cells + some basal epithelium stem cells)
CD3 - T-lymphocytes (cells outside of lymphoid follicles)
CD5 - T-cells
CD45 - all lymphocytes are labeled
Describe the reservoir FXN of lymphatic and other organs WRT monocytes and neutrophils
- Monocytes - stored in spleen in white pulp - recruited from there following a MI
- Neutrophil - proliferation occurs in marrow - storage occurs in lung because has a huge area of capillary walls and can afford to store a lot of them - neutrophils adhere to alveolar capillaries
Describe the Thymus
= a primary lymphatic organ
- where t-lymphocytes mature
- sits in mediastinum (adventitia)
- involutes with age (like in bone marrow)
What are tonsils
- site of lymphocyte exposure to foreign substances
what are lymph nodes
- region where “experienced peripheral lymphocytes are exposed to “naive” systemic ones
what is the spleen
- functions as lymphatic tissue for blood
- has most complicated structure (compared with thymus, tonsils, lymph nodes)
Lymphocytes - birth place and site of maturation?
- born in the marrow
- eneter circulation at marrow sinuses (b-lymphocytes enter as “mature” cells ready to react with antigens - there initial cell development + specification is in the bone marrow)
- compared with t cells ( born in bone marrow + briefly enter circulation –> sequestered to thymus to complete maturation)
Describe the thymus
- surrounded by capsule of CT
- divided into lobes
- each lobe has two parts
1) outer portion = thymic cortex
2) inner portion = thymic medulla
Thymocyte
= immature lymphocyte that is acquiring t-cell receptors + ability to bind non-self MHC molecules
- once in immuno-compartment can only leave by passing into medulla and out through medullary circulation
Epithelioreticular cells
= stromal cells of thymus
- in both cortex + medulla
- their cytoplasm is eosinophilic
hassall’s corpuscles
= thymic corpuscles
- in thymic medulla (not cortex)
= sheets of squamous ERCs piled up like skin of onion
6 types of ERCs that can be classed using antibody staining, location, and sublet details of morphology
I) LIning capsular/pervascular spaces of organ
II + III + IV) within the cortex
V, VI) within the medulla (type VI- contributes to hassal’s corpuscles)
Lymphoid follicles
- b-cells (antibody mediated immunity) - congregate in the middle of the follicles
- lymphoid follicles contain germinal centers = evidence of clonal expansion
- the t-cells (MHC-mediated immunity) sit outside the follicles
Tonsils
- have reticulated epithelium
= ring of lymphatic material + associated overlying epithelia - surround opening of the pharynx
-sit midline and are grossly symmetrical structures - most common = pharyngeal tonsils (=adenoids) + palatine tonsils
- FXN: allow lymphocytes access to potential ingested foreign substances
- have tonsilar crypts (folds of epithelium)
Reticulated epithelium
= epithelium that lacks many desmosomal attachments
- allows CT cells to invade epithelial cell layers and into lumen of the tonsilar crypts
Tonsilar crypts
= folds of tonsilar epithelium
- FXN = provide sampling of ingested food in close proximity + for extended period of time
what histologic feature distinguishes the Palantine tonsil
= oral epithelium overlying it
what histological feature distinguishes the Paryngeal tonsil
= respiratory epithelium lining it
Intraepithelial lymphocyte
= lymphocyte seen histologically within an epithelial layer
- seen also in the ileum, gall bladder, epididymus, tonsils, among other places
Describe lymph nodes
- stromal tissue = a minor fraction of volume of the organ
= places where lymphocytes from circulation can interact with those from periphery - are within CT spaces surrounded + separated by dense CT capsule
- lymph enters via afferent lymphatic vessels + leaves through efferent lymphatic vessels
- systemic circulation has the greatest volume circulation through the nodes
- all lymphocytes must return to circulation through efferent lymphatics
Describe both the anatomical and physiologist view of the divisions of the lymph nodes
1) Anatomical A) Cortex - no blood vessels - lymphoid follicles B) paracortex C) Medulla 2) Physiologist view A) mesenchymal space - cortex - paracortex (clusters of T-cells) - medullary cords (clusters of B-cells) B) lymphatic circulation -lymphatics -medullary sinuses (open spaces) C) systemic circulation
where are Afferent lymphatics found
= lymphatics outside capsule or those traversing it
- branch into sub capsular sinuses
where are Subcapsular sinuses found
= beneath the capsule
- branch from the afferent lymphatics
- branch into peritrabecular sinuses
Where ar the peritrabecular sinuses found
= in the CT walls extending down from the capsule
What is the marginal zone
= interface of red + white pulp
= the place where blood “leaves” systemic circulation
What is red pulp
- region that has a volume divided evenly between A) the mesenchymal space (=splenic cords)
and
B) vascular space (=splenic sinuses)
Describe a trabecular artery
= artery running within the trabeculae
- surrounded by dense CT
Describe the central artery
- surrounded by white pulp –> known are the peri-arterial lymphatic sheath (PALS)
Describe the trabecular vein
- vein found within the trabeculae
- surrounded by dense CT
List the open circulation route of the spleen
1) Splenic artery
- large artery supplying the spleen
2) Trabecular artery
- runs within the dense CT of the trabeculae
3) Central artery
- surrounded by white pulp (PALS)
4) Radial artery
- branch from central artery
- traverse the region of the PALs
5) Penicillar arteries
- smallest vessels of the arterial vascularization of the spleen
- exist within the marginal zone
6) sheathed capillaries
- surrounded by macrophages
- occur in the marginal zone
- blood leaves the endothelial lined spaces from these vessels
7) Splenic sinus
- blod returns to endothelial lined space through these
- take up large percentage of red pulp’s volume
8) trabecular vein
- found within the dense CT tabeculae
9) splenic vein
- large anatomical vein draining the spleen
