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Inflammation 3 Flashcards

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1
Q

You do an impression smear on a mass and see a bunch of neutrophils and bacteria. Is this most likely acute or chronic?

A

Acute

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2
Q

What are the cardinal signs of inflammation?

A

Heat, redness, swelling, pain, and loss of function

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3
Q

What does sepsis mean?

A

Bacteria and/or bacterial products in the blood stream

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4
Q

If a neonatal calf is septic, what is likely the bacterial route of entry?

A

Ascending umbilical infection (omphalophlebitis)

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5
Q

What are the 5 R’s of inflammation?

A 
Recognition of the injurious agent
Recruitment of leukocytes
Removal of the agent
Regulation of the response
Resolution or repair
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6
Q

What happens during recognition?

A

Variety of sentinel cells recognize pathogens or cellular damage

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7
Q

What sentinel cells are involved in recognition?

A

Mast cells, dendritic cells, and macrophages

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8
Q

What is a macrophage called if it’s in the liver?

A

Kupffer cell

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9
Q

What is a macrophage called if it’s in the lung?

A

Alveolar macrophages

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10
Q

What is a macrophage called if it’s in the skin?

A

Langerhans cell

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11
Q

What is a macrophage called if it’s in the brain?

A

Microglia

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12
Q

What do cell receptors recognize?

A

PAMPs (pathogen-associated molecular patterns)

DAMPs (damage-associated molecular patterns)

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13
Q

Where are PAMPs located?

A 
Plasma membrane (detect extracellular microbes)
Cytosol (detect intracellular microbes)
Endosomes (detect ingested microbes)
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14
Q

Where are DAMPs located?

A

Typically cytosolic since they are looking for cellular damage

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15
Q

What does TLR4 (toll-like receptor 4) recognize?

A

LPS (endotoxin)

So, TLR4 is on the cell surface

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16
Q

TLR3 recognizes some viruses. Where on the sentinel cell might TLR3 be?

A

Intracellular (endosomes or cytosolic). Think viral recognition or ingested products

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17
Q

Leukocytes (and erythrocytes) normally flow in the middle of a vessel. Here, they’ve approached the vessel wall. What is the term called?

A

Margination

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18
Q

What is migration into the tissues called?

A

Chemotaxis

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19
Q

Why do RBCs and WBCs generally flow in the middle of a vessel?

A

Blood flow is faster in the center (sheer forces from the vessel wall cause friction)

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20
Q

What causes margination?

A

Slowing of blood flow (vasodilation)

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21
Q

What causes vasodilation?

A

Chemical mediators, notable histamine

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22
Q

What cell is responsible for releasing histamine?

A

Macrophages

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23
Q

What steps are involved in the first phase of recruitment?

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A

Luminal margination, rolling and adhesion to activated endothelium

24
Q

What happens during the rolling step of the first phase of recruitment?

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A

Leukocytes transiently (loosely) adhere, detach, and bind again until firm

25
What molecules are expressed during the rolling phase of recruitment?
Adhesion molecules called selectins (and integrins)
26
What kind of binding do selectins have?
Low affinity binding. They just loosely bind and help things slow down
27
What ligand is present that will interact with the selectin molecules during the rolling phase of recruitment?
Sialyl-Lewis-X-modified glycoproteins
28
What induces the expression of selectins and their ligands during the rolling phase of recruitment?
Cytokines (TNF, IL-1) and Histamine and thrombin
29
What do histamine and thrombin do during the rolling phase of recruitment?
They redistribute P-selectin in endothelial cells to the surface
30
What do type I IFNs do?
They increase transcription of cytokines
31
What happens during the adhesion phase of recruitment?
Leukocytes that have rolled along the endothelial surface and loosely adhered now become firmly adhered
32
What molecules are expressed during the adhesion phase of recruitment?
Integrins
33
What kind of binding do integrins have?
high affinity binding (firm adhesion!)
34
What ligands are expressed during the adhesion phase of recruitment? What do they bind to?
VCAM-1 on the endothelial cell binds integrin VLA-4 ICAM-1 on the endothelial cell binds LFA-1 and Mac-1
35
What causes ligands to be expressed during the adhesion phase of recruitment?
Expression is induced by TNF, IL-1, and chemokines
36
If we lack VCAM-1 and ICAM-1, what will happen?
Loss of these can lead to adhesion problems
37
What are integrins activated by?
Chemokines - tells integrins to increase their affinity
38
What do leukocytes do after firm adhesion takes place during recruitment?
The leukocytes spread out on the endothelial surface
39
What are Leukocyte Adhesion Deficienies (LADs)?
Lack of functional expression of B2-integrins on leukocytes. So, we increase our circulating neutrophils, but they can't adhere and exit the bloodstream, they can't firmly adhere
40
What are two classic examples of Leukocyte Adhesion Deficiencies (LADs)?
Holstein cattle (BLAD) and Irish Setters
41
What will Leukocyte Adhesion Deficiencies (LADs) lead to?
Recurrent infections - they can't recover from something even minor
42
What are the cytokines we've discussed?
TNF and IL-1
43
What is the term for migration across the vessel wall?
Diapedesis
44
What drives diapedesis?
Chemokines
45
Where are adhesion molecules located?
In the intracellular junctions between endothelial cells
46
What are some of the adhesion molecules that aid in migration across the vessel wall?
PECAM-1 (CD31), JAM A, B, and C, and CD99
47
What is migration into the tissues driven by?
Chemokines
48
Cell movement is directed in response to a what?
Chemoattractant - bacteria, typically they're endogenous though
49
What are the two types of chemoattractants?
Exogenous - bacterial products Endogenous - cytokines (chemokines), complement, and arachidonic acid metabolites
50
How long does it take our first responders, neutrophils and monocytes, to arrive?
Neutrophils: 6-24 hours Monocytes: 24-48 hours
51
Give an example of a receptor that binds to a PAMP.
TLR (Toll-like receptor)
52
Are cytokines prepackaged?
No, a signal goes to the nucleus to increase the transcription rate of the cytokines (not like histamine)
53
Define Leukocytosis.
Too mnay leukocytes in the blood
54
What is neutrophilia?
Too many neutrophils in the blood
55
A juvenile Irish Setter presents to your clinic. He seems sick a lot of the time and doesn't seem to heal from minor injuries. You perform a CBC and note a leukocytosis and more specifically a neutrophilia. You also do a blood smear and see numerous neutrophils. What do you think might be occurring in this dog?
Leukocyte Adhesion Deficiency (LAD)
56
What is defective in LAD?
Integrins
57
What are integrins involved with? a. margination b. rolling c. adhesion d. migration
Adhesion (firm)

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