6. Histology and Cell Biology of Lymphatics Flashcards
Functions of the Lymphatic System
1. Production and distribution of lymphocytes: – Primary and secondary lymphoid organs
2. Maintenance of normal blood volume and
chemical composition of the interstitial fluid:
– Drainage system: Returns excess interstitial fluid back to the blood, preventing ____, the excess accumulation of
fluid around tissues.
3. Alternative route for the transport of hormones,
nutrients and waste:
– E.g.: In the intestine, lymphatic capillaries (____)
transport absorbed fat from the small intestine to the blood stream.
edema
lacteals
Organization of the Lymphatic System
• Lymphatic Vessels:
– Capillaries (or Terminal Lymphatics)
– Collecting Vessels
• Lymphoid Tissues and Organs (see Foundation Sciences I,
module 3, for a refresher in Immunology):
– Primary Lymphoid Organs - Produce the cell components of
the immune system:
• ____
• ____
– Secondary Lymphoid Organs and Tissues - Where immune
responses occur:
• Lymphoid Organs:
– ____
– ____
• Lymphoid Tissues:
– ____
– ____
– ____
bone marrow
thymus
lymph nodes
spleen
tonsils
gut-associated lymphatic tissue (GALT)
diffuse lymph nodules
The Lymphatic Vessels
• Range from lymphatic capillaries to large-diameter lymphatic ducts.
• Lymphatic endothelium lacks ____:
– “Leaky”: Allows entry of high molecular weight molecules (e.g. albumin).
• In ____, muscular contraction: opening of spaces for uptake of cell debris, pathogens, and cancer cells.
• In the intestine: absorption of ____ and transport to the blood stream.
• Fluid movement – ____ way flow:
– ____ contraction: SMCs in vessel wall contract in response to lymph filling (peristaltic pump effect) and opening/closure of valves.
– ____ contraction: contraction of surrounding muscles and respiratory movements.
• Lymphatics connect peripheral tissue (interstitial volume) with the venous
○ Lymphatic ducts transporting from tissues to return fluid to circulation
○ Venous > low pressure
§ High pressure of arterial would push lymphatic fluid backwards
• Traffic occurs in the capillaries
○ ____ will always occur at this level
○ Formation of ____ (slide 5)
tight junctions inflammation lipoproteins one intrinsic extrinsic
leakage of fluid
edema
Histology of the Lymphatic Capillaries • \_\_\_\_ (sacs), small diameter vessels that collect the lymph in peripheral tissues. • Structure: • Endothelium with little or no \_\_\_\_. • \_\_\_\_ outline. • Anchored to surrounding CT by \_\_\_\_. ---• \_\_\_\_ fibers.
blind-ended basal lamina irregular anchoring filaments elastic
Histology of the Lymphatic Capillaries
• Lymphatic structures end up in a ____
○ Not ____ like circulatory vessels
• Lined by endothelium lacking ____
○ Also lacking a BL
• Whenever capillary bed is present
○ ____ from blood plasma into interstitial space of tissues
§ Osmotic pressure
○ Capillaries reabsorb fluid in interstitial space into the collecting lymphatics and into the thoracic duct
• Anchoring filaments
○ Attach to collagen fibers in regular tissue
○ Prevent ____ of capillaries
§ Very ____ pressure
§ Surrounded by fluid
§ Maintain tubes in an ____ conformation
• Histology
○ Look like “holes” within tissue, surrounded by “nothing”
○ ____ shape - do not have high abundance of muscle and collapse
§ Small veins have a similar morphology in terms of shape
○ Diagnosis doesn’t mean if you don’t see RBC you assume it’s definitely a ____
§ Must look closer at the entire structure
blind-ended sac continuous tight junctions leakage of fluid collpase low open irregular lymphatic
• Diagnostic: Only the lumen of ____ and ____ may contain RBCs.
arterioles
venules
Lymphatic Collecting Vessels • Largest lymph vessel – thoracic duct: \_\_\_\_ mm diameter • Tunica Intima: • Smooth endothelium. • \_\_\_\_ valves to prevent fluid backflow. • Tunica Media: • Very \_\_\_\_. • SM and elastic fibers. • Tunica Adventitia: • \_\_\_\_, inconspicuous. • CT with collagen and elastic fibers. • Attaches lymphatic vessels to other underlying tissues: \_\_\_\_.
• Semilunar valves are similar to those seen in smaller diameter \_\_\_\_ • TI ○ Leaky • TM ○ Essentially \_\_\_\_ in this kind of vessel • TA ○ Produces elastic fibers (anchoring filaments) and collagen to which they attach
4-6 semilunar thin thin anchoring filaments
veins
non-existant
Lymphatic Collecting Vessels: Fluid Movement
- Lymphangion: ____ of the lymphatic system, segment between two ____ valves in a vessel.
- Fluid movement: ↑ lymph pressure due to ____ or ____ contraction → valve opening → lymph moves into next chamber → drop in ____ → valve closing → no backwards flow.
• Mechanism also applies to small veins • Movement of fluid is induced by: ○ Contraction of SM around tissue ○ Contraction of \_\_\_\_ around tissue § Compress lymphatic capillaries, pushing unidirectionally
functional unit semilunar filling SMC pressure
skeletal tissue
Lymphoid Tissues and Organs – Primary Lymphoid Organs - Produce the \_\_\_\_ of the immune system: • \_\_\_\_ • \_\_\_\_ – Secondary Lymphoid Organs and Tissues - Where \_\_\_\_ responses occur: • Lymphoid Organs: – \_\_\_\_ – \_\_\_\_ • Lymphoid Tissues: – \_\_\_\_ – \_\_\_\_ – \_\_\_\_
cell components
bone marrow
thymus
immune lymph nodes spleen tonsils gut-associated lymphatic tissue (GALT) diffuse lymph nodules
Primary Lymphoid Organs: Thymus
• Primary lymphatic tissue, located in the midline of the body, above the ____.
• Maturation of ____ cells.
• Greatest size at ____: decreases in size as
functional cells die and are replaced by
fibrous CT and adipose.
Morphology: – Two lobes divided into \_\_\_\_ lobules. – Surrounded by a CT \_\_\_\_. – CT from capsule continues into \_\_\_\_ (pl. of trabeculum). – Two histological regions: • Cortex • Medulla
• Cortex ○ Outside of tissue ○ Within CT • Medulla ○ Center of tissue • Both regions \_\_\_\_ differently, and are different in \_\_\_\_ composition
heart
T
puberty
incomplete
capsule
intralobular traceula
stain
cellular
Primary Lymphoid Organs: Thymus • Morphology: – \_\_\_\_ cortex with abundant \_\_\_\_ (thymocytes). – Cortex shows NO \_\_\_\_. – Less basophilic medulla, with \_\_\_\_. – Stromal cells of \_\_\_\_ origin. – Highly \_\_\_\_: capillaries.
• Medulla ○ More eosinohpilic § Binds eosin ○ More \_\_\_\_ § Fewer \_\_\_\_ • Stroma/parenchyma is epithelial in origin ○ Most other lymphoid organs are \_\_\_\_ cells § Fibroblasts
basophilic T lymphocytes lymphatic nodules Hassall's corpuscles epithelial vascularized
protein
nuclei
reticular
The Thymic Cortex
• Large number of ____
○ Single T lymphocyte
§ ____ within the tissue
§ >90% of lymphocyte is the ____
• Highly vascularized
○ Lymphocytes immigrate from regular ____
• Cortical epithelial cells
○ Composition of the thymus (epithelial)
○ Lymphocytes aren’t the only cell-type present
• Trabeculae from CT capsule
○ Stain ____
§ Like medulla
○ High abundance of ____
nuclei
“thymocytes”
nuclei
circulatory capillaries
red
ECM
A Diagnostic Thymic Structure: The Medullary Hassall’s Corpuscle
• Made up of \_\_\_\_ cells ○ \_\_\_\_ § The end-stage § Dead • Highly keratinized show the deepest \_\_\_\_ in stain • These cells cannot be shed off like keratinized cells on skin ○ Instead, form a corpuscle § \_\_\_\_ depository • Corpuscle vs BV ○ BV § Full of \_\_\_\_ § Very different structure • Can see them at low magnification • Only present within the \_\_\_\_
epithelial keratinized red waste RBC medulla
Reminder: T-cell Selection in the Thymus
• Positive and Negative selection of T cells to recognize foreign antigens:
– Positive selection allows only those T cells that are able to bind to self-MHC molecules in the thymus to mature. Positive selection results in ____.
–Negative selection removes T cells whose TCR strongly recognize (high affinity) self-MHC + self-antigen. Die by ____ within the thymus. Negative selection results in ____.
• Differentiate between T cells ○ CD4/CD8 antigens • During selection: ○ Double-positive ○ And then selected to individual antigens
MHC restriction
apoptosis
self-tolerance
Cellular Organization of the Thymus • Cortex: – Locus of T-cell selection: Immature T cells. – Branched cortical epithelial cells. – Macrophages. • Medulla: – Mature T cells. – Medullary epithelial cells. – Macrophages. – Dendritic cells.
• Process of selection takes place in \_\_\_\_ ○ Both for and against § Apoptosis is occurring due to double-negative • Double-negative located in the outer cortex ○ Close to \_\_\_\_ ○ Immature • During selection, becoming double and single-positive ○ Deeper and deeper within \_\_\_\_ • Single-positive will migrate into circulation, into \_\_\_\_
cortex
capsule
cortex
medulla
The Thymus-Blood Barrier
- Ensures that antigens from the blood do not react with maturing T cells, to prevent autoimmune reactions.
- Formed by:
- ____ cells.
- ____ cells.
- ____ basal lamina.• T cells are selected against in response to autoantigens
○ Via apoptosis
○ Would create AID if not eliminated
• Plenty of proteins circulating in blood (not necessarily foreign)
○ Leak into cortex:
§ Would be interpreted in selected process as foreign antigens, and would be selected to respond against
• In order to section stroma of thymus from circulation:
○ Thymus-blood barrier
• ____ capillary within the thymus
○ Surrounded by ____ cells
○ ____basal lamina
§ ____ cells produce their own BL in addition to the one produced by ____ cells (like in normal BV)
§ Not leaky at all
§ Isolates the capillary
§ Selection of T-cells takes place w/o problems
endothelial
cortical epithelial
dual
continuous cortical epithelial dual cortical epithelial epithelial
Secondary Lymphoid Organs: Lymph Nodes
• Size: 1-25 mm.
• Filtration and purification of the lymph before it reaches the bloodstream:
• Antigen ____ and lymphocyte ____.
• Stroma composed of ____ cells.
• Structure: • Cortex: • Outer region. • Lymphatic \_\_\_\_ with \_\_\_\_ centers. • Venules with \_\_\_\_ cells: ---• More \_\_\_\_ than regular endothelium. ---• Facilitate lymphocyte \_\_\_\_.
• Medulla:
• Deeper in the node.
• ____:
—• Macrophages and plasma cells.
• Cortex ○ Lymphatic nodules § Not present in \_\_\_\_
recognition
proliferation
reticular (fibroblast)
nodules germinal high endothelial columnar diapedesis
medullary cords
thymus
Secondary Lymphoid Organs: Lymph Nodes
• Capsules turn into \_\_\_\_ ○ Deep within the \_\_\_\_ (past the cortex as well) • Cortex ○ Outer cortex § Lymphatic \_\_\_\_ □ High proliferation of \_\_\_\_ cells □ In response to antigen, selected B cells are induced to \_\_\_\_ to form a clonal population ® Produce specific type of \_\_\_\_ ○ Inner cortex (more blue) § Mostly \_\_\_\_ cells □ Previously selected within the \_\_\_\_
• Medulla
○ Medullary cords
§ Surround medullary ____
• ____ lympathic vessels (1) carry lymph into the node
• Travels into ____ sinus, and deep into organ via ____ sinus (close proximity to trabeculae)
○ PT sinus > medulla > medullary sinuses
• Lymph leaves via ____, in an area named the hilum
• Capillary system that vascularizes the entire node
○ Via the ____
○ ____ venule
§ Different endothelium from regular endothelium of ____
□ Lymphocytes can leave the ____, and enter the nodes so they can recognize antigen
□ Migrate throughout the ____, that allows the easy passage of cells
trabeculae
medulla
nodules
B
prolfierate
Ig
T cells
thymus
sinuses afferent subcapsualr paratrabecular efferent hilum high endothelial capillaries
circulation
stroma
Remember this? Categories of Connective Tissue: Reticular CT
• Cells: Fibroblasts (a.k.a. reticular cells)
• Fibers:
– Reticular fibers of ____ collagen.
– Thin and ____.
– Fibers form a mesh that allow ____ of cells and fluid.
• Present only in the ____ of lymphoid organs: lymph nodes, spleen, hematopoietic bone marrow.
• Most CT produce \_\_\_\_, this is different
Type III branched passage stroma Type I
Secondary Lymphoid Organs: Lymph Nodes
• Surrounded by a CT capsule.
• Trabecula: extensions of the capsule CT into the
cortical and medullary regions.
- Cortex:
- Outer cortex:
- Mostly ____ cells.
- Lymphatic ____ (cell proliferation).
- Inner cortex:
- Mostly ____ cells.
- No lymphatic ____.
- Medulla:
- Medullary ____
- Medullary ____
- Outer cortex is ____
- Medullary sinuses are spaces between ____
B cells
nodules
T
nodules
cords
sinuses
basophilic
medullary cords
Lymph Node: Cortex
• Trabecula extending from the ____.
- Subcapsular sinuses:
- Lymph ____ spaces.
- Under the ____.
- Paratrabecular sinuses:
- Extensions of the ____ sinuses into the ____.
- Continue into the medulla as ____.
• Lymphatic ____.
• Germinal center ○ Proliferation of \_\_\_\_ cells takes place
capsule circulation capsule subcapsular cortex medullary sinuses nodules
B
Lymph Node: High Endothelial Venules
- HEVs:
- Allow lymphocyte ____ from the bloodstream.
- Tall, thick ____ cells.
- ____ basal lamina.
- Express ____ (lymphocyte chemo-attractants).
• Normal venule ○ Flat endothelium (squamous) ○ Thin BL • High endothelial venule ○ \_\_\_\_ ○ Thicker BL ○ \_\_\_\_ ○ Not easy to identify
diapedesis
endothelial
thick
chemokines
cuboidal
leakier
The Lymph Node: Structure and Function of a Lymphatic Nodule (or Follicle)
- Lymphatic nodules consist of ____ where activated B cells proliferate.
- ____ display antigens. B cells accumulate in the ____ zone.
- Macrophages phagocytose rejected (low-affinity Ig) B cells. B cells with high-affinity Ig migrate to the medullary cords, differentiate into ____ (IgG secretion) and leave the lymph node through efferent lymphatic vessels.
- ____ (type III collagen).• Lymphatic nodule
○ Two main substructures:
§ ____-zone
□ Rich in mature B cells, clonal cells derived from activated B cells
□ Eventually differentiate into plasma, enter medulla via medullary cords
□ Release Ab onto the lymph
§ ____ center
□ Proliferation and activation of B cells
germinal centers follicular dendritic cells mantle plasma cells reticular fibers
mantle
germinal
Lymph Node: Medullary Region
• Medullary cords:
• ____
• ____ cells.
• Medullary sinuses:
• Branching.
• Surrounded by the medullary cords.
• Continuation of the cortical
____ sinuses.
• Confluent with the subcortical sinuses at
the ____ to form the ____ lymphatic vessel.
• Nothing similar to the lymphatic nodules within the \_\_\_\_
macrophages
plasma
paratrabecular
hilum
efferent
thymus
