Exam 1: Dr. Kaplan Inflammation: Mechanisms 1 Flashcards
1
Q
What are the roles of inflammation?
A
Deliver additional effector molecules and cells to infection site
Augment the killing of microorganisms
Induce local blood clotting to provide a physical barrier to spread of infection
Promote repair of injured tissue
2
Q
What are the signs of inflammation?
A
Rubor (redness) Tumor (swelling) Calor (heat) Dolor (pain) Functio Laesa (loss of function)
3
Q
What is acute inflammation often like?
A
Self-limiting
4
Q
What is the onset of actue inflammation like?
A
Quick
5
Q
What is the resolution of inflammation like?
A
Often quick
6
Q
What does acute inflammation predominantly involve?
A
The innate immune system
7
Q
What is tissue injury like with acute inflammation?
A
Mild
8
Q
How apparent are local and systemic signs of acute inflammation?
A
Obvious
9
Q
When can chronic inflammation occur?
A
If the pathogen is adapted to resist antimicrobial mechanisms
10
Q
What are the processes of chronic inflammation like?
A
Diverse, dependent on the pathogen
11
Q
What is the onset of chronic inflammation like?
A
Can be days to years
12
Q
What does chronic inflammation often involve?
A
Adaptive immune response
13
Q
What are signs of chronic inflammation like?
A
Subtle or absent, but tissue injury can be severe
14
Q
When does adaptive immunity begin?
A
When T cells come into play
15
Q
What is the most common initiator of acute inflammation?
A
Sentinel cell detection of PAMPs
16
Q
What are the typical sentinel cells in tissues?
A
Macrophages
17
Q
Once activated, what do macrophages synthesize and release?
A
Cytokines and chemokines
18
Q
What are some examples of cytokines?
A
IL-1β
IL-6
TNF-α
19
Q
What do cytokines do?
A
Signal other inflammatory cells or blood vessels in the area
20
Q
What is an example of chemokines?
A
CXCL8
21
Q
What do chemokines do?
A
Recruit other inflammatory cells to the area
22
Q
What is the most common trigger of inflammation?
A
Microbial infections
23
Q
What other tissue insults can initiate inflammation?
A
Trauma
Physical or chemical injury
Foreign bodies
Inappropriate products of adaptive immunity
24
Q
What does sterile inflammation often result in?
A
Release of endogenously produced DAMPs, which activate macrophages
25
What are examples of sterile inflammation?
Liver ischemia/reperfusion following surgery or acute myocardial infarction
26
What is an inflammasome?
Multi-subunit complex of proteins that cleave IL-1β and IL-18
27
What does an inflammasome typically conatin?
Sensor protein
Adaptor protein
Enzyme that cleaves IL-1β and IL-18 from their pro form to their active form
28
In addition to cytokines and chemokines, what are inflammatory processes regulated by?
Eicosonoids
29
What are eicosonoids?
Fatty acid derivatives
30
What are 2 kinds of eicosonoids?
Leukotrienes
| Prostaglandins
31
What are eicosonoids synthesized from?
Membranes following liberation of arachidonic acid from diacylglycerols or phospholipids
32
What are prostaglandins synthesized from?
Arachidonic acid by cyclooxygenase enzymes
33
What are the different cyclooxygenase enzymes?
COX-1 and COX-2
34
How is COX-2 induced? COX-1?
Induced in inflammation
| It is constitutive
35
What does PGE2 do?
Vascular permeability and vasodilation
36
What are leukotrienes synthesized from?
Arachidonic acid by lipoxygenase
37
What does LTB4 do?
Chemoattractant for neutrophils
38
What do LTB4 and LTD4 do?
Vascular permeability
39
What are examples anti-inflammatories and anti-pyretics?
Meloxicam
Phenylbutazone
Carprofen
40
What is meloxicam selective for?
Slight selectivity for COX-2
41
What is phenylbutazone used in?
Horses
42
What is carprofen selective for?
COX-2
43
What do anti-pyretics do?
Help with fever
44
What kind of vascular changes can cause inflammation?
Vasodilation
Increased blood flow
Increased vascular permeability
Expression of cell-adhesion molecules on vascular endothelium
45
What does vasodilation occur through?
The action of inflammatory mediators on arteriole and postcapillary venule smooth muscle
46
In vasodilation, what does the decreased tone to smooth muscle do?
Widens the lumen of the vessels
47
What does the widening of the vessels in vasodilation do?
Slows blood flow in the area
48
What is vasodilation mediated by?
Histamine and 5-HT (serotonin; mast cells), PGE2 (macrophages and mast cells), and nitric oxide (endothelium)
49
What does vasodilation contribute to? How?
Both rubor and calor by increasing blood volume
50
What do PAMPs, DAMPs, macrophages, mast cells, inflammatory mediators, and inflammatory molecules act on? What does it do?
Acts on blood vessel to make it bigger
51
What does increased vascular permeability occur through?
The action of inflammatory mediators on endothelial cells
52
What does increased vascular permeability form?
An exudate that moves from vasculature to affected interstitial tissue
53
What does increased vascular permeability contribute to?
Blood flow stasis
54
What does endothelial cell contraction during increased vascular permeability cause?
Gaps in the tight junctions between endothelial cells
55
What are other mechanisms for increased permeability?
Transcytosis
| Direct damage to enothelial cell layer
56
What is transcytosis?
Active transport of fluid and macromolecules across the endothelial cell cytoplasm through vesicles
Another way to form pores for cells and mediators to get through
57
What is the first cell to respond when there is an infection?
Neutrophils; however, macrophages are the resident cell so they are there initially and then release something to attract the neutrophils
58
What are the 4 stages of leukocyte extravasation?
Tethering and rolling
Firm adhesion and crawling
Transmigration
Chemotaxis through tissue
59
What is tethering?
IL-1 and TNF-α activate endothelial cells to express adhesion molecules to which neutrophils can bind
60
What does E-selectin bind to?
Sialylated Lewis-X modified glycoprotein
61
What does P-selectin bind to?
Platelet selectin glycoprotein ligand 1
62
What are the interactions like during tethering?
Low affinity but many interactions increases the strength of binding neutrophils and endothelial cells
63
What are integrin interactions like?
Initially low affinity, but switch to high affinity
64
What does ICAM-1 bind to?
LFA-1
65
What will the high affinity interaction during firm adhesion do?
It will stop the neutrophil from rolling
66
What is transmigration?
Movement of leukocytes from lumen of blood vessel through the vessel wall and into interstitium
67
Where does transmigration usually occur?
In thin-walled postcapillary venules, but neutrophils still have to penetrate the endothelial barrier and underlying basement membrane
68
Where do neutrophils typically transmigrate?
Through small gaps between endothelial cells and digest basement membrane with collagenase
69
Once out of the vasculature, what do neutrophils do?
Respond to chemical gradients to move to the site of infection
70
What are endogenous products produced by?
Innate cells
71
Where do exogenous microbial products diffused from?
The site of infection
72
What do neutrophils do once in the tissue?
Adopt an amoeboid-like morphology with a leading pseudopod
73
What do receptors for chemoattractants on the pseudopod bind? What does it do?
The liagand and moves the rest of the cell toward the stimulus
74
What happens as the neutrophil moves toward infection?
It becomes activated in response to cytokines or other pro-inflammatory mediators making it more efficient at its primary functions
75
What are macrophages called in the liver?
Kupffer cells
76
What are macrophages called in the lung?
Alveolar macrophages
77
What are macrophages called in the CNS?
Microglial cells
78
What are macrophages called in the spleen?
Splenic macrophages
79
What does the type of cellular response depend on?
Pathogen
| Types of adhesion molecules that are expressed
80
What will neutrophils be recruited in response to?
CXCL8
81
What will eosinophils be recruited in response to?
CCL11
82
What will monocytes differentiate into once in the tissue?
Macrophages and further migrate toward the insult
83
What are functions of macrophages?
Moderately proficient at killing
Phagocytose and break down debris
Clean up dead neutrophils, debris and dead microbes
84
What are examples of systemic effects of inflammation? (9)
```
Loss of appetite
Altered sleep patterns
Lethargy
Muscle wasting
Hemodynamic changes
Fever
Leukocytosis
Metabolic acidosis
Alterations in acute phase proteins
```
85
What are examples of cytokines?
TNF-α
IL-1
IL-6
86
What do cytokines do?
Rapidly disseminate throughout the body
| Function to conserve energy and mobilize proteins
87
What does TNF-α cause?
Loss of apepetite
Altered sleep patterns
Lethargy
Cachexia
88
What can TNF-α and IL-1 stimulate?
Hypothalamus to produce PGE2
89
What does the release of PGE2 in anterior hypothalamus do?
Acts on thermoregulatory neurons to cause fever
90
What are the targets of inflammatory mediators that change the response from acute to systemic?
Bone marrow
Brain
Liver
91
What is PGE2 a main player in?
Fever and vascular permeability
92
Know the different proposed functions of fever
Know the different proposed functions of fever
93
What is leukocytosis?
Increased number of leukocytes circulating in the blood
94
What is leukocytosis known as in response to acute systemic inflammation?
Neutrophilia
95
What does neutrophilia cause?
Increased release of neutrophils from bone marrow
96
What does neutrophilia allow for?
More neutrophils to extravasate and contribute to immune defense at site of infection
97
What will a prolonged release of neutrophils from bone marrow do?
Deplete its store of mature cells prompting increased neutrophil production, but less mature neutrophils
Causes a left shift
98
What does a severe left shift in neutrophil maturation cause?
Acute inflammatory response
99
What can acute systemic inflammation do?
Alter the serum acute phase proteins profile
100
What does positive serum APP profile do?
Increase with inflammation
101
What does negative serum APP profile do?
Decrease with inflammation
102
Why are APPs used as diagnostic indicators of inflammation?
Because they can be induced so quickly and with high magnitude
103
What does an opsonin do?
Helps macrophages phagocytose
104
What are the positive APPs?
```
C-reactive protein
Serum amyloid A
Haptoglobin
Alpha-1-acid glycoprotein
Ceruloplasmin
Hepcidin
Fibrinogen
```
105
What are the negative APPs?
Albumin
| Transferrin
106
What do APPs do?
Act as opsonins and activate complement
107
What is C-reactive protein a major APP in?
Dogs and pigs
108
What is serum amyloid A and major APP in?
Dogs
Cats
Cattle
Pigs
109
What is haptoglobin a major APP in? Moderate?
Pigs, cattle, sheep
| Dogs, cats
110
What is alpha-1-acid glycoprotein a major APP in? Moderate?
Cats
| Dogs
111
What is ceruloplasmin a moderate APP in? Minor?
Dogs
| Cattle
112
What is fibrinogen important in?
Horses and cattle
