6. Histology and Cell Biology of Lymphatics Flashcards

1
Q

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.

A

edema

lacteals

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2
Q

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:
– ____
– ____
– ____

A

bone marrow
thymus

lymph nodes
spleen

tonsils
gut-associated lymphatic tissue (GALT)
diffuse lymph nodules

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3
Q

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)

A
tight junctions
inflammation
lipoproteins
one
intrinsic
extrinsic

leakage of fluid
edema

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4
Q
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.
A
blind-ended
basal lamina
irregular
anchoring filaments
elastic
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5
Q

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

A
blind-ended sac
continuous
tight junctions
leakage of fluid
collpase
low
open
irregular
lymphatic
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6
Q

• Diagnostic: Only the lumen of ____ and ____ may contain RBCs.

A

arterioles

venules

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7
Q
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
A
4-6
semilunar
thin
thin
anchoring filaments

veins
non-existant

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8
Q

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
A
functional unit
semilunar
filling
SMC
pressure

skeletal tissue

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9
Q
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: 
– \_\_\_\_
– \_\_\_\_ 
– \_\_\_\_
A

cell components
bone marrow
thymus

immune
lymph nodes
spleen
tonsils
gut-associated lymphatic tissue (GALT)
diffuse lymph nodules
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10
Q

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
A

heart
T
puberty

incomplete
capsule
intralobular traceula

stain
cellular

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11
Q
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
A
basophilic
T lymphocytes
lymphatic nodules
Hassall's corpuscles
epithelial
vascularized

protein
nuclei
reticular

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12
Q

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 ____

A

nuclei
“thymocytes”
nuclei

circulatory capillaries
red
ECM

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13
Q

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  \_\_\_\_
A
epithelial
keratinized
red
waste
RBC
medulla
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14
Q

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
A

MHC restriction
apoptosis
self-tolerance

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15
Q
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 \_\_\_\_
A

cortex
capsule
cortex
medulla

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16
Q

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
A

endothelial
cortical epithelial
dual

continuous
cortical epithelial
dual
cortical epithelial
epithelial
17
Q

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 \_\_\_\_
A

recognition
proliferation
reticular (fibroblast)

nodules
germinal
high endothelial
columnar
diapedesis

medullary cords
thymus

18
Q

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

A

trabeculae
medulla

nodules
B
prolfierate
Ig

T cells
thymus

sinuses
afferent
subcapsualr
paratrabecular
efferent
hilum
high endothelial
capillaries

circulation
stroma

19
Q

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
A
Type III
branched
passage
stroma
Type I
20
Q

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 ____
A

B cells
nodules

T
nodules

cords
sinuses

basophilic
medullary cords

21
Q

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
A
capsule
circulation
capsule
subcapsular
cortex
medullary sinuses
nodules

B

22
Q

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
A

diapedesis
endothelial
thick
chemokines

cuboidal
leakier

23
Q

The Lymph Node: Structure and Function of a Lymphatic Nodule (or Follicle)

  1. Lymphatic nodules consist of ____ where activated B cells proliferate.
  2. ____ display antigens. B cells accumulate in the ____ zone.
  3. 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.
  4. ____ (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
A
germinal centers
follicular dendritic cells
mantle
plasma cells
reticular fibers

mantle
germinal

24
Q

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 \_\_\_\_
A

macrophages
plasma

paratrabecular
hilum
efferent

thymus

25
Q

General Organization of the Spleen
1. Capsule:
____ CT with collagen, elastic fibers,
SMCs.

  1. Trabecula:
    ____ CT derived from the capsule.
    Trabecular artery and vein.
  2. White pulp:
    Splenic lymphoid ____: B and T cells, APCs.
  3. Red pulp:
    Splenic ____: filled with blood
    Splenic ____: plates of lymphoid tissue, (a.k.a. ____).
A
contractile
branching
nodules
sinusoids
cords
cords of billroth
26
Q
Secondary Lymphoid Organs: Spleen
 • \_\_\_\_ secondary lymphoid organ:
– Blood \_\_\_\_: removes aged/damaged RBCs and microorganisms from bloodstream.
– Storage of \_\_\_\_ from broken-down RBCs.
– Initiation of \_\_\_\_ response.

• Structure:
– Not ____ into cortex and medulla.
– No ____ lymphatic vessels.
– Stroma made up of ____ cells (fibroblasts) and fibers.

• Two components:
– White Pulp: ____ component.
– Red Pulp:____ component.

A

largest
filter
iron
immune

differentiated
afferent
reticular

immune
bloodstream

27
Q

General Organization of the Spleen

• Similar capsule to \_\_\_\_
	○ Protrudes into stroma of organ, forming \_\_\_\_ (branch from outer capsule)
	○ Contains SMC and elastic fibers
		§ \_\_\_\_
		§ Blood stored in red pulp can be induced to travel back into \_\_\_\_ via spleen capsule
			□ Not a big deal in humans (doesn't store a lot of blood)
			□ \_\_\_\_ animals (seals, etc.)
				® Store so much blood
				® Before diving, they squeeze \_\_\_\_ dramatically, and export blood from spleen into circulation
					◊ Thereby capturing more \_\_\_\_
	• White pulp
		○ Similar to lymphatic \_\_\_\_ in lymph nodes
			§ Germinal center
				□ Surrounded by \_\_\_\_
			§ Central \_\_\_\_
				□ Surrounded by T cells
			§ \_\_\_\_ + lymphatic \_\_\_\_
				□ Diagnostic of spleen
• Red pulp
	○ Splenic \_\_\_\_
		§ Surrounded by splenic \_\_\_\_
	○ Everything that is stained is the splenic cords (similar to medullar cords)
A

lymph nodes
trabeculae
contracle
circualtion

diving
spleens
oxygen

nodules
corona
arteriole

central arteriole
nodule

sinusoids
cords

28
Q

General Ogranization of the Spleen: White and Red Pulp

1. White pulp:
\_\_\_\_ (a.k.a. Central Artery).
\_\_\_\_ (periarteriolar lymphoid sheath). 
Splenic nodules:
Germinal \_\_\_\_
\_\_\_\_ (B cells and APC)
2. Red pulp:
Components:
\_\_\_\_ (paintbrush-like) arteriole. 
\_\_\_\_-sheathed capillaries. 
Splenic \_\_\_\_.
\_\_\_\_ cells (forming the splenic sinusoids).
\_\_\_\_ circulating cells.

White and red pulp interact at the ____ zone.

A

central arteriole
PALS
center
corona

penicillar
macrophage
sinusoids
reticular
blood-derived

marginal

29
Q

Splenic White Pulp

• Splenic nodules:
– Central arteriole with \_\_\_\_
(periarteriolar lymphoid sheath).
– Germinal \_\_\_\_.
– Corona (\_\_\_\_ cells and \_\_\_\_s).
• Central arteriole does not have to be located within the \_\_\_\_ of the nodule
A

PALS
center
B
APCs

center

30
Q

Relationship between White Pulp and Red Pulp

  1. ____ artery enters spleen along a trabeculum.
  2. In the white pulp the artery gets a sheath of ____ (PALS) and becomes the ____ artery (or arteriole).
  3. ____: Central arteriole, PALS, corona and germinal center.
  4. Central artery branches into ____ arterioles, and
    ends in the ____ sinus.• Trabecular artery
    ○ From ____ arteries
    ○ Branches, and penetrates the white pulp (1)
    § Here, becomes surrounded by T cells/PALS
    • Marginal sinus surrounds the entire lymphatic ____
    • Radial arterioles dump into ____ sinus
    • Leaving the white pulp: ____ lymphatic vessels (part of ____ pulp)
A
trabecular
T cells
central
white pulp
radial arterioles
marginal

splenic
nodule

marginal
efferent
red

31
Q

The Splenic White Pulp: Antigen Presentation

  1. Antigens enter from the ____ (not from the ____) and reach the ____ pulp.
  2. Antigen-presenting cells (APCs) in the ____ detect and process antigens; then interact with PALS-derived ____ cells. T cells activate ____ cells, which proliferate and differentiate into ____ cells.
  3. Plasma cells release ____ into the ____.

• Blood from the marginal sinus and radial arterioles continues into the ____ arterioles which end in ____ of the ____ pulp.

A
blood
lymph
white
corona
T cells
B
plasma
Ig
bloodstream

penicillar
macrophage-sheathed capillaries (MSCs)
red

32
Q

Relationship between White Pulp and Red Pulp

  1. Blood from the marginal sinus and radial arterioles continues into the ____ arterioles ending in macrophage-sheathed capillaries (MSCs) of the red pulp.
  2. MSCs drain either into:
    – Splenic sinusoids (____ circulation).
    – Stroma of the red pulp (____ circulation).• Penicillar arterioles
    ○ Looking like a brush; many hairs
    ○ Sheathed by ____
    § Responsible for eliminating old and damaged ____
    § MSCs
    • End up in red pulp
    • Drains into two different compartments:
    ○ Closed circulation
    § MSCs end up into splenic sinusoids, surrounded by splenic cords
    § Drain into vein capillaries, veins, to be drained out of spleen
    § Returns to the ____ circulation
    ○ Open circulation
    § Vessels are open-ended
    § Migrate of vessels, back into the stroma of the ____ pulp
    □ That’s why it stays so red!
    □ The cavities are filled with RBC
    □ ____ component of the spleen
    • MSCs are tough to identify - impossible
    • MSCs continue into splenic sinusoids (closed circulation), which are also surrounded by ____
A

penicillar
closed
open

macrophages
RBC
general

red
storage

macro’s

33
Q
The Splenic Red Pulp: Splenic Sinusoids
  • \_\_\_\_ capillaries:
– Endothelial cells: \_\_\_\_-shaped (not
flat), separated by \_\_\_\_
(discontinuous endothelium).
– Discontinuous \_\_\_\_: ring-
like strands.
– \_\_\_\_ fibers: ring-like strands
of collagen.

• ____ passage of RBCs through the
sinusoidal wall.
• Macrophages take up and destroy
particles and cellular debris: blood ____.

• The endothelial cells (rod-shaped) are separated by slits
	○ Not tight
	○ Discontinuous: endothelium and BL are discontinuous
		§ BL are reduced to fibers
	○ Macro's can extend \_\_\_\_ through the slits and actually touch the RBC
		§ Find old/damaged
			□ Phagocytose
• Part of the \_\_\_\_ circulation
• Involved in regulation of \_\_\_\_ homeostasis/RBC biology
A
discontinuous
rod
slit spaces
basal lamina
reticular

easy
filtering

pseudopods
closed

iron