Fiser.13.Inflammation Flashcards
1
Q
what three processes occur with endothelial injury?
A
exposed collagen; platelet-activating factor release; tissue factor release
2
Q
what substance is released from the endothelium when platelets bind to collagen
A
PDGF (platelet-derived growth factor) is released
3
Q
what cells are recruited by endothelial release of PDGF?
A
recruits PMNs and macrophages
4
Q
What cell type has the dominant role in wound healing?
A
macrophages
5
Q
what three substances are released by macrophages that causes its dominant role in wound healing?
A
growth factors (PDGF), cytokines (IL-1, TNF-alpha)
6
Q
what two cell types are attracted by PDGF and what do they cause?
A
PDGF is chemotactic and activates inflammatory cells (PMNs and macrophages) and fibroblasts (causing collagen and ECM proteins)
7
Q
what effect does PDGF have on blood vessels?
A
causes angiogenesis
8
Q
what effect does PDGF have on epithelial cells?
A
causes epithelialization
9
Q
what effect does PDGF have on smooth muscle cells?
A
chemotactic for smooth muscle cells
10
Q
what effect does PDGF have on wound healing?
A
shown to accelerate wound healing
11
Q
name three effects of epidermal growth factor (EGF)
A
chemotactic and activates fibroblasts (collagen and ECM proteins); angiogenesis; epithelialization
12
Q
name three effects of fibroblastic growth factor (FGF)
A
chemotactic and activates fibroblasts (collagen and ECM proteins), angiogenesis, epithelialization
13
Q
what type of molecule is platelet-activating factor?
A
its a phospholipid
14
Q
where is platelet-activating factor generated?
A
it is generated by phospholipase in the endothelium
15
Q
what is the effect of platelet-activating factor (2)?
A
chemotactic for inflammatory cells; increases adhesion molecules
16
Q
name six chemotactic factors for inflammatory cells
A
PDGF, IL8, LTB4, C5a, C3a, PAF
17
Q
name three chemotactic factors for fibroblasts
A
PDGF, EGF, FGF
18
Q
name five angiogenesis factors
A
PDGF, EGF, FGF, IL8, hypoxia
19
Q
name three epithelialization factors
A
PDGF, EGF, FGF
20
Q
how long do PMNs last in tissues
A
PMNs last 1-2 days in tissue
21
Q
how long do PMNs last in blood?
A
PMNs last 7 days in blood
22
Q
How long do platelets last in blood?
A
last 7-10 days in blood
23
Q
what type of lymphocyte is involved in chronic inflammation?
A
T-cells
24
Q
what type of lymphocyte is involved in antibody production?
A
B cells
25
Which WBC is involved in type I hypersensitivity reaction
eosinophils
26
what type of receptors are on eosinophils and how does it affects its ability to take part in allergic reactions / type I hypersensitivity reactions?
IgE receptors that bind to allergen
27
what chemical is released by eosinophils and how does this stimulate the immune system?
eosinophils release major basic protein, which stimulates basophils and mast cells to release histamine
28
in what type of infection are eosinophils increased?
increased in parasitic infections
29
what is the major source of histamine in the blood?
basophils
30
are basophils present in tissue?
nope
31
what is the primary cell in type I hypersensitivity reactions?
mast cells
32
what is the major source of histamine in tissue?
mast cells
33
name three effects of histamine on tissues and capillaries (3)?
vasodilation, tissue edema, postcapillary leakage
34
what is the primary effector in type I hypersensitivity reactions?
histamine
35
Name four systemic effects of bradykinin
peripheral vasodilation, increased permeability, pain, pulmonary vasoconstriction
36
what is the function of angiotensin-converting enzyme and where is it located?
ACE inactivates bradykinin and is located in the lungs
37
what is the amino acid precursor for nitric oxide?
arginine
38
what is the enzyme that catalyzes the synthesis of nitric oxide and what is its substrate?
nitric oxide synthase converts arginine to nitric oxide
39
name the two reactions that occur in the endothelium that causes nitric oxide to vasodilate
NO activates guanylate cyclase, increases cGMP, resulting in vascular smooth muscle dilation
40
what is an alternative name for nitric oxide?
endothelium-derived relaxing factor
41
how does endothelin affect the vascular system?
causes vascular smooth muscle constriction (opposite effect of nitric oxide)
42
name the two main initial cytokine response to injury and infection
TNF alpha and IL-1
43
what cell is the largest producer of TNF-alpha
macrophages
44
what is the effect of TNF alpha on adhesion molecules?
increases adhesion molecules
45
what is the effect of TNF-alpha on coagulation?
procoagulant
46
what is the effect of TNF-alpha on cancer patients?
causes cachexia in patients with cancer
47
what is the effect of TNF alpha on other WBCs?
activates neutrophils and macrophages --\> more cytokine production and cell recruitment
48
name two systemic effects of high levels of TNF-alpha?
causes circulatory collapse and multisystem organ failure
49
what is the major source of IL-1?
macrophages
50
what does IL-1 synergize with?
synergizes with TNF-alpha
51
what are the effects of IL-1? (3)
similar to TNF-alpha: increased adhesion molecules, procoagulant, activates neutrophils and macrophages
52
which interleukin causes fever?
IL-1
53
how does IL-1 cause fever?
mediated by PGE2 in the hypothalamus by raising the thermal set point
54
What is the MOA of antipyretic NSAIDs?
reduces PGE2 synthesis, which is responsible for increasing the thermal set point in the hypothalamus
55
What is the MOA of fever with atelectasis?
alveolar macrophages cause fever with atelectasis by releasing IL-1
56
what proteins are stimulated for release by IL-6 (2)?
IL-6 stimulates increased hepatic acute phase proteins (C-reactive protein and amyloid A)
57
what cell type releases interferons and why?
released by lymphocytes in response to viral infection
58
what are the three cell types activated by interferons?
activates macrophages, natural killer cells, and cytotoxic T-cells
59
how do interferons affect viruses?
inhibits viral replication
60
what is the most potent stimulus for hepatic acute phase response proteins?
IL6
61
what is the function of C-reactive protein?
opsonin, activates complement
62
name 7 hepatic acute phase response proteins that are increased with IL6
CRP, amyloid A, amyloid P, fibrinogen, haptoglobin, ceruloplasmin, alpha-1 antitrypsin, C3 (complement)
63
name 3 hepatic acute phase response proteins that are decreased with IL6
albumin, pre-albumin, transferrin
64
where are L-selectins located?
located on leukocytes
65
where are E-selectins located?
endothelium
66
where are P-selectins located?
platelets
67
how do L-selectins, E-selectins, and P-selectins interact to allow for rolling adhesion
L-selectins on leukocytes bind to E-selectins on endothelium and P-selectins on platelets, causing rolling adhesion
68
where are beta-2 integrins located?
on leukocytes
69
what is the function of beta-2 integrins?
bind ICAMs and function in anchoring adhesion
70
where are ICAM, VCAM, PECAM, and ELAM located?
on endothelial cells
71
what is the function of ICAM, VCAM, PECAM, and ELAM? (2)
bind to beta-2 integrin molecules located on leukocytes and platelets. Also involved in transendothelial migration.
72
\*\*PHOTO\*\* describe the four steps of leukocyte recruitment
1) circulating leukocytes express integrins in low-affinity conformation; 2) exposure to activated endothelium leads to rolling mediated by L-selecting/P-selectin on neutrophils and E-selectin on endothelium; 3) leukocyte exposure to cytokines released by macrophages phagocytosing pathogens induces high-affinity integrin conformation --\> tight lieukocyte-nedothelial adhesion withintegrin; 4) exposure to chemokines leads to diapedesis mediated by beta1 and beta2 integrins
73
what are the three complement factors are present only in the classic pathway?
C1, C2, C4
74
how is the classic complement pathway activated?
IgG or IgM with antigen-antibody complex activation
75
what are the two stimuli for the alternative complement pathway
endotoxin or bacteria
76
what are three factors only found in the alternate complement pathway?
factors B, D, and P (properdin)
77
what is the complement factor that is common to both classic and alternative pathways and functions as its convergence point?
C3
78
what chemical is required for both classic and alternative complement pathways?
Magnesium
79
name three complement anaphylatoxins
C3a, C4a, C5a
80
what are the four systemic effects of complement anaphylatoxins
C3a, C4a, C5a --\> increased vascular permeability, bronchoconstriction, activate mast cells, basophils
81
what complement factors create the membrane attack complex?
C5b-9b
82
what is the function of the membrane attack complex created by complement?
cell lysis (usually bacteria) by creating a hole in cell membrane
83
define opsonization
targets antigen for immune response
84
name two complement factors that act as opsonins
C3b and C4b
85
name two complement factors that cause chemotaxis for inflammatory cells
C3a and C5a
86
what is the precursor for prostaglandins
produced from arachidonic precurosrs
87
name four systemic effects of PGI2
vasodilation, increased vascular permeability, bronchodilation, inhibit platelets
88
name four systemic effects of PGE2
vasodilation, increased vascular permeability, bronchodilation, inhibit platelets
89
what is the MOA of NSAIDs anti-inflammatory action?
reversible COX (cyclooxygenase) inhibitor
90
what is the MOA of aspirin's anti-inflammatory action
irreversible COX (cyclooxygenase) inhibitor
91
what is the MOA of platelet inhibition by aspirin?
inhibits platelet adhesion by decreasing TXA2
92
what is the MOA of steroids' anti-inflammatory action?
inhibit phospholipase (converts phospholipids to arachidonic acid) --\> inhibits inflammation
93
what is the precursor for leukotrienes?
produced from arachidonic precurosrs
94
what are the systemic effects of LTC4, LTD4, and LTE4 (leukotrienes) (2)
slow-reacting substances of anaphylaxis; bronchoconstriction, vasoconstriction followed by increased permeability (wheal and flare)
95
what is the effect of LTB4 (leukotriene)
chemotactic for inflammatory cells
96
when do catecholamines peak after injury?
peak 24-48 hours after injury
97
where is norepinephrine released from?
released from sympathetic postganglionic neurons
98
where are epinephrine and norepinephrine released from?
released from adrenal medulla (neural response to injury)
99
describe the pathophysiology of the neuroendocrine response to injury (6 hormones)
afferent nerves from site of injury --\> stimulate CRF (corticotropin releasing factor), ACTH, ADH, growth hormone, epinephrine, and norepinephrine release
100
what role do thyroid hormones play in injury/inflammation
no major role in injury or inflammation
101
what is the role of CXC chemokines in inflammation (3)
chemotaxis, angiogenesis, wound healing
102
name two CXC chemokines
IL8, platelet factor 4
103
what does the "C" in CXC chemokines stand for?
cysteine
104
what does the "X" in CXC chemokines stand for?
another amino acid
105
what process results in oxidant generation?
inflammation (from main producer oxidase)
106
what enzyme produces the superoxide anion radical (O2-)
NADPH oxidase
107
what enzyme produces hydrogen peroxide (H2O2)?
xanthine oxidase
108
what is the cellular defense against superoxide anion radicals?
superoxide dismutase converts it to hydrogen peroxide
109
what enzyme protects against hydrogen peroxide
glutathione peroxidase / catalse
110
what cells are the primary mediator of reperfusion injury?
PMNs
111
what is the pathophysiology of chronic granulomatous disease?
NADPH-oxidase system enzyme defect in PMNs results in reduced superoxide radical formation
