Inflammation Flashcards
1
Q
inflammation
A
the process of rxn of living vascularized tissue to injury.
Is usually beneficial (destroy invaders, prepare injured tissue for repair) but sometimes induces tissue damage
2
Q
central events in inflammation involve
A
blood vessels:
- increased blood flow
- increased vascular permeability
- leukocyte exudation through vessels
3
Q
repair
A
process by which lost or necrotic cells are replaced by vital cells
4
Q
regeneration
A
replacement by cells of the same type
5
Q
scarring or fibrosis
A
replacement by connective tissue. Does not occur in brain
6
Q
2 processes of repair
A
regeneration and scarring/fibrosis
7
Q
5 signs of acute inflammation
A
1) rubor (redness)
2) tumor (swelling) (doesn’t refer to neoplasia)
3) calor (heat)
4) dolor (pain)
5) functio laesa (loss of function
8
Q
hyperemic
A
increased blood flow to an area. Causes rubor
9
Q
chemical mediators of inflammation from PLASMA
A
1) Kinins: bradykinin
2) Complement fragments: C5a
3) Coagulation/Fibrinolytic products
10
Q
chemical mediators of inflamm. from CELLS AND TISSUE:
A
1) vasoactive amines: histamine, serotonin
2) prostaglandins and leukotrienes: PGE2, LTB4
3) cytokines/chemokines: TNF-a, IL-1,IL-8, MIP-1
4) nitric oxide
11
Q
3 major components of acute inflammation
A
1) vascular changes in flow and caliber
2) increased vascular permeability
3) leukocytic events (margination, adhesion/migration, chemotaxis and activation)
12
Q
steps in vascular changes in flow and caliber during inflamm.
A
1) transient vasoconstriction (neurally mediated, short term)
2) vasodilation (mediated by PGE2, histamine, NO; long term)
13
Q
mechanism of increased vascular permeability during inflamm.
A
- endothelial contraction (most common and short-lived*)
- direct endothelial injury (i.e. toxins, burns)
- leukocyte-endothelial injury (i.e. during sepsis)
- increased transcytosis
- endothelial proliferation (angiogenesis) and leak (immature blood vessels are leaky)
14
Q
gaps due to endothelial contraction affects venules or arterioles?
A
venules
15
Q
increased transcytosis is mediated by what?
A
Vascular endothelial-derived growth factor (VEGF)
16
Q
Which mechanism of increased vascular permeability is the only mech. to affect arterioles and capillaries in addition to venules?
A
direct injury (all others only affect venules)
17
Q
Where in leukocyte movement out of blood vessel do selectins act? Integrins?
A
- selectins help leukocytes roll along blood vessel
- integrins help leukocytes adhere and transmigrate through vessels
18
Q
leukocytic margination and rolling is mediated by:
A
selectin molecules on endothelial cells and oligosaccharides on leukocytes
19
Q
What mediators upregulate selectin?
A
TNF-a, IL-1
20
Q
selectin is composed of?
A
single chain carb-binding glycoprotein
21
Q
leukocyte adhesion is mediated by:
A
Endothelium: ICAM-1, VCAM-1 (adhesion moleucules)
Leukocytes: integrins (LFA-1, Mac-1, VLA-4)
22
Q
What mediators upregulate integrin?
A
TNF-a, IL-1, IL-8
23
Q
leukocytic transmigration is mediated by:
A
PECAM-1 (CD31) (a homophilic adhesion molecule expressed on both endothelium and leukocytes)
24
Q
leukocyte adhesion deficiencys involves what in animals?
A
integrins (integrins AND selectins in humans)
25
Bovine Leukocyte adhesion deficiency (BLAD)
- defect in CD18 expression on leukocytes due to homozygous D126G allele
- causes poor neutrophil response to infection
- decreased survival, enteritis, pneumonia
26
chemotaxis
cell migration along a concentration gradient of chemical mediator
27
chemokinesis
random migration stimulated by a mediator
28
first cells to respond to inflammation
neutrophils
29
what do neutrophils release?
-superoxide anion and lysosomal enzymes (which can induce tissue damage)
30
neutrophil half-life in circulation
6-7 hours
31
macrophage lifespan
30-60 days
32
what do macrophages release (among others)?
- superoxide anion and lysosomal enzyme (can contribute to tissue damage)
- IgA to recruit neutrophils
- growth factors for scar formation
33
macrophages derive from
monocytes or local division
34
what do macrophages form?
epitheliod cells and multinucleated cells
35
what do macrophages modulate?
inflammatory, immune, and repair processes through mediators and cytokines
36
component of eosinophils that make it effective killer of helminths
major basic protein
37
eosinophils are component of many hypersensitivity diseases and mediate tissue damage in chronic rxns
:)
38
fx of IL-5
prolongs tissue survival
39
How is inflammation classified?
by:
duration (acute, subacute, chronic)
distribution (focal, multifocal, locally-extensive, diffuse)
type of exudate (serous, fibrinous, suppurative, etc...)
tissue involved (hepatitis, nephritis, encephalitis, etc...)
40
types of exudate
```
serous
fibrinous
suppurative
eosinophilic
hemorrhagic
necrotizing
lymphocytic
proliferative
granulomatous
Mixed: fibrinonecrotic, fibrinopurulent
```
41
mast cells contain what preformed mediators?
histamine and serotonin
42
mast cells are a major source of:
leukotrienes, cytokines, chemokines
43
Fx of mast cells
- bind IgE and other Ab --> degranulate and release mediators when Ag binds
- mediate hypersensitivity disease
44
functions of all lymphocytes
- regulator/effector of Ag-driven inflammatory processes
| - produce cytokines that modulate inflammation and immunity (interleukins, gamma-interferon)
45
Which lymphocytes produce Ab?
B cells, plasma cells
46
Which lymphocytes mediate helper activity and cytotoxicity?
T cells
47
what do platelets release?
-release serotonin, PAF, growth factors (PDGF, TGF-beta, FGF)
48
morphologic diagnosis
diagnosis based solely on morphology (i.e. chronic diffuse granulomatous enteritis
49
etiologic diagnosis
dx including causative agent (i.e. - intestinal mycobacteriosis)
50
hallmark of chronic reaction
fibrosis/scarring
| occurs beyond 10-14 days
51
acute inflamm. char. by:
- hours to days
- changes in vessel permeability and flow
- leukocyte exudation
52
subacute inflamm. char. by:
- several days to 7-10 days
- tissue cell proliferation
- NO fibrosis
53
fibrinous responses are often char. by:
- acute bacterial infection with marked increase in vascular permeability
- clotting proteins leak out and initiate coag cascade and fibrin formation in large amounts
54
fibrinopurulent = mix of:
fibrin and neutrophils
55
erosion
defect assoc. with necrosis that goes down to level of basement membrane
56
ulcer
defect assoc. with necrosis that goes down to level below BM into deep connective tissue (goes further than erosion!)
57
what can cause granulomatous inlammatory response?
macrophage dominated inflammatory response results in thickening
58
fungi usually induce what response?
necrosis, hemorrhage (granulomas if severe)
59
nematodes usually induce what response?
granulomatous
60
3 mediators of vasodilation*
PGE2, histamine, NO
61
mediators of vascular permeability*
```
histamine
C3a
C5a
bradykinin
leukotrienes C4, D4, E4, PAF
```
62
mediators of chemotaxis/activation*
```
IL-8
C5a
LTB4
microbial products
fibrinopeptides
```
63
3 mediators of fever*
IL-1
TNF-alpha
PGE2
64
2 mediators of pain*
bradykinin
| PGE2
65
2 mediators of tissue damage*
lysosomal enzymes
| oxygen radicals
66
Basic chars. of mediators of inflamm.
- produced in response to stimuli
- one mediator can stimulate release of others
- short lived
- functions overlap (redundancy)
67
How is bradykinin formed?
Factor 12 activates prekallikrein --> kallikrein, which cleaves kinnogen to bradykinin
68
bradykinin fx
vasodilation, increased vascular permeability, pain (via stimulation of free nerve endings), smooth m. contraction
69
C5a effects
- chemotactic for neutrophils
- neutrophil activation
- mast cell degranulation
- increased vascular permeability
70
C3a effects
-increased vascular permeability
71
how does fibrinogen get cleaved?
- by plasmin and streptokinase after activation of thrombin via intrinsic/extrinsic pathways
- fibrin formed is chemotactic for neuts and macs
72
Which chemokine attracts mainly neutrophils?**
IL-8
73
Which chemokines attracts mainly monocyte/macrophages/T-lymphocytes?**
MIP-1a, RANTES, MCP-3
74
Which chemokine attracts mainly eosinophils?**
Eotaxin
75
2 vasoactive amines
histamine and serotonin
76
sources of histamine
mast cells, basophils (platelets)
77
histamine actions
- vasodilation
- increased vascular permeability
- bronchial and other smooth m. contraction
78
What do LTB4/C4/D4/E4 all have in common?
- slow releasing substances of anaphylaxis
- increase vascular permeability
- chemotactic for neutrophils
79
steroid down/upregulates arachidonic acid
downregulates
80
what converts AA to prostaglandin? What inhibits this?
cyclooxygenase; inhibited by COX-1 and 2 inhibitors, aspirin
81
what converts AA to leukotriene?
5-lipoxygenase
82
cyclooxygenase source
resident cells, leukocytes, mast cells
83
PGE2 action
- increase vascular flow, permeability
| - fever, pain
84
PGD2 action
- increase vascular flow, permeability
| - smooth m. contraction in some tissues
85
cyclooxygenase products
prostaglandins
86
source of LTB4
neuts, macs, eos
87
LTB4 action
- chemotactic for neuts and eos
| - chemokinesis for macs
88
"big three" molecules that are chemotactic for neuts*
LTB4, C5a, IL-8
89
source of LTC4/D4/E4
-neuts, macs, eos
90
action of LTC4/D4/E4
- increase vascular perm.
| - smooth m. contraction
91
Source of Lipoxin A4 and B4 (LXA4 and LXB4)
transcellular biosynthesis by neuts and platelets
92
action of lipoxin A4 and B4
inhibit leukocyte adhesion and chemotaxis
93
name 2 cytokines
IFN-y, TNF-a
94
sources of IFN-y
T-cells, NK cells (stimulated by Ag, early immune response)
95
IFN-y actions
UPREGULATE MAC FX:
- increase superoxide production/killing capacity
- induce IL-12 and Th1 shifted immune response
- upreg. class II MHC: inc. Ag presentation
- upreg. growth factors
- giant cell formation
96
sources of TNF-a
macs, fibroblasts, etc. (stim. by endotoxin, bacteria, virus, protozoa, toxins)
97
actions of TNF-a
The primary role of TNF is in the regulation of immune cells
- upreg. E-selectin and inc. thrombogenicity of endothelial cells
- enhance mac interleukins and NO
- induce acute phase rxn proteins
- induce fibroblast proliferation and collagen synthesis
- fever
- cachexia by appetite suppression and lipoprotein lipase inhib.
- apoptosis in selected cells
98
source of chemokines
macs, stromal cells, epithelial cells
99
chemokine stimuli
virus, bacteria, toxins, protozoa, cytokines
100
name 4 potent mediators of increased vascular permeability*
- bradykinin
| - LTC4/D4/E4
101
Name 2 things that mediate pain perception*
PGE2, bradykinin
102
3 main mediators of vasodilation***
PGE2, histamine, NO
103
main mediators of vascular permeability***
```
histamine
C3a
C5a
bradykinin
leukotrienes C4,D4,E4
PAF
```
104
main mediators of chemotaxis/activation***
```
IL-8
C5a
LTB4
microbial products
fibrinopeptides
```
105
3 main mediators of fever***
IL-1
TNF-a
PGE2
106
2 main mediators of tissue damage***
lysosomal enzymes
| oxygen radicals
107
clinical/pathophysiologic systemic events of inflammation
- loss of tissue fx
- poor weight gain/weight loss
- fever
- leukocytosis
- acute phase reactants via TNF, IL-1, IL-6
108
sequelae of acute inflamm. if stimulus is REMOVED
- resolution of inflamm.
| - repair of tissue
109
sequelae of acute inflamm. if stimulus PERSISTS
- chronic inflamm.
- repair and tissue damage
- scarring
110
chronic inflamm.
inflamm. that results from injurious stimuli that are persistent and leads to predominantly proliferative and scarring, rather than exudative, reaction. Hallmark = fibrosis or scarring
111
what inflamm. cells predominate in chronic inflamm?
macs, lymphocytes, plasma cells. Neuts may continue to be present
112
granulomatous inflamm.**
inflammatory process dominated by macrophages
113
granuloma
compact and organized collection of mononuclear inflamm. cells dominated by macs
114
Char. of stimuli of granulomatous inflamm.**
1) particulate substance resisting lysosomal degradation
| 2) induce T-cell hypersensitivity
115
Types of stimuli for granulomatous inflamm.**
- inert particles
- lipids and waxes
- resistant microbes
- high MW polymers
- Ag inducing T-cell hypersensitivity
116
cells of the granulomatous inflamm. rxn
- monocytes
- macs
- epitheliod cells (secrete lysosomal enzymes and toxic O radicals)
- MNGCs
117
3 types of granulomatous inflamm. rxns**
granulomatous: macs +/- epitheliod cells, giant cells
simple granuloma: compact inflamm. cell exudate
complex granuloma: granuloma w/ central necrosis +/- calcification
118
granulomatous inflamm. is usually acute/chronic?**
chronic (unless there is pre-existing T cell hypersensitivity)
119
Type I allergic rxn mediator/mech/dz ex.**
mediator: IgE, IgG
mech: mediator release
Dz: anaphylaxis
120
Type II allergic rxn**
mediator: IgM, IgG
mech: cytotoxicity, dysfunction
dz: autoimmune, hemolytic anemia
121
Type III allergic rxn**
mediator: IgM, IgG
mech: immune complex
dz: glomerulonephritis
122
Type IV allergic rxn**
mediator: T cells, cell mediated
mech: contact dermatitis, immunity
dz: mycobacteriosis, TB, contact dermatitis, transplant reject,viral cytopathology
123
what do activated T cells produce in type IV hypersensitivity rxn?
IFN-y to activate macs, which then differentiate into giant cells and epithelioid macs
