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Gen Path > Inflammation 3 > Flashcards

Inflammation 3 Flashcards

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?

A

Luminal margination, rolling and adhesion to activated endothelium

24
Q

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

A

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

25
Q

What molecules are expressed during the rolling phase of recruitment?

A

Adhesion molecules called selectins (and integrins)

26
Q

What kind of binding do selectins have?

A

Low affinity binding. They just loosely bind and help things slow down

27
Q

What ligand is present that will interact with the selectin molecules during the rolling phase of recruitment?

A

Sialyl-Lewis-X-modified glycoproteins

28
Q

What induces the expression of selectins and their ligands during the rolling phase of recruitment?

A

Cytokines (TNF, IL-1) and Histamine and thrombin

29
Q

What do histamine and thrombin do during the rolling phase of recruitment?

A

They redistribute P-selectin in endothelial cells to the surface

30
Q

What do type I IFNs do?

A

They increase transcription of cytokines

31
Q

What happens during the adhesion phase of recruitment?

A

Leukocytes that have rolled along the endothelial surface and loosely adhered now become firmly adhered

32
Q

What molecules are expressed during the adhesion phase of recruitment?

A

Integrins

33
Q

What kind of binding do integrins have?

A

high affinity binding (firm adhesion!)

34
Q

What ligands are expressed during the adhesion phase of recruitment? What do they bind to?

A

VCAM-1 on the endothelial cell binds integrin VLA-4

ICAM-1 on the endothelial cell binds LFA-1 and Mac-1

35
Q

What causes ligands to be expressed during the adhesion phase of recruitment?

A

Expression is induced by TNF, IL-1, and chemokines

36
Q

If we lack VCAM-1 and ICAM-1, what will happen?

A

Loss of these can lead to adhesion problems

37
Q

What are integrins activated by?

A

Chemokines - tells integrins to increase their affinity

38
Q

What do leukocytes do after firm adhesion takes place during recruitment?

A

The leukocytes spread out on the endothelial surface

39
Q

What are Leukocyte Adhesion Deficienies (LADs)?

A

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
Q

What are two classic examples of Leukocyte Adhesion Deficiencies (LADs)?

A

Holstein cattle (BLAD) and Irish Setters

41
Q

What will Leukocyte Adhesion Deficiencies (LADs) lead to?

A

Recurrent infections - they can’t recover from something even minor

42
Q

What are the cytokines we’ve discussed?

A

TNF and IL-1

43
Q

What is the term for migration across the vessel wall?

A

Diapedesis

44
Q

What drives diapedesis?

A

Chemokines

45
Q

Where are adhesion molecules located?

A

In the intracellular junctions between endothelial cells

46
Q

What are some of the adhesion molecules that aid in migration across the vessel wall?

A

PECAM-1 (CD31), JAM A, B, and C, and CD99

47
Q

What is migration into the tissues driven by?

A

Chemokines

48
Q

Cell movement is directed in response to a what?

A

Chemoattractant - bacteria, typically they’re endogenous though

49
Q

What are the two types of chemoattractants?

A

Exogenous - bacterial products

Endogenous - cytokines (chemokines), complement, and arachidonic acid metabolites

50
Q

How long does it take our first responders, neutrophils and monocytes, to arrive?

A

Neutrophils: 6-24 hours

Monocytes: 24-48 hours

51
Q

Give an example of a receptor that binds to a PAMP.

A

TLR (Toll-like receptor)

52
Q

Are cytokines prepackaged?

A

No, a signal goes to the nucleus to increase the transcription rate of the cytokines (not like histamine)

53
Q

Define Leukocytosis.

A

Too mnay leukocytes in the blood

54
Q

What is neutrophilia?

A

Too many neutrophils in the blood

55
Q

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?

A

Leukocyte Adhesion Deficiency (LAD)

56
Q

What is defective in LAD?

A

Integrins

57
Q

What are integrins involved with?

a. margination
b. rolling
c. adhesion
d. migration

A

Adhesion (firm)

Gen Path (5 decks)

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