Ch2: Acute and Chronic Inflammation Flashcards
(214 cards)
1
Q
Inflammation is fundamentally what type of response?
A
Protective
2
Q
Two main components of inflammation?
A
- Blood vessels
2. Leukocytes
3
Q
What triggers inflammation?
A
Soluble factors produced by cells or derived from plasma proteins
4
Q
Is inflammation acute or chronic?
A
Both
5
Q
Acute inflammation is due to what cells?
A
PMN’s
6
Q
Chronic inflammation is due to what cells?
A
Lymphocytes
7
Q
Subacute inflammation is due to what cells?
A
Eosinophils
8
Q
When is inflammation terminated?
A
When offending agent is eliminated
9
Q
What are some harmful effects of inflammatory response? 2
A
- Anaphylactic response
2. Chronic disabling diseases
10
Q
Anaphylactic shock can be induced by what?
A
- allergies
- bug bites
- certain drugs
11
Q
What is the main component of bee venom?
A
Melittin
12
Q
What does melittin stimulate?
A
Phospholipase A2
13
Q
Five features of inflammation in latin and english
A
- Calor = heat
- Rubor = redness
- Tumor = swelling
- Dolor = pain
- functio laesa = loss of function
14
Q
3 main components of acute inflammation?
A
- Increased blood flow through change in vessel size (heat, redness)
- Leaky vessels (swelling)
- Recruitment of leukocytes to injury and their activation (pain, loss of function)
15
Q
What are 4 acute inflammation stimuli?
A
- Infections/toxins
- tissue necrosis
- Foreign bodies
- Immune reactions
16
Q
What receptors recognize certain bacteria, viruses, and fungi?
A
Toll-like receptors
17
Q
Tissue necrosis can be caused by what? 4
A
- ischemia
- trauma
- physical and chemical injury
- Hypoxia
18
Q
What is exudation?
A
Escape of fluids proteins and blood cells from vascular system into the interstitial tissue or body cavities
19
Q
What is exudate?
A
High protein content (specific gravity greater than 1.020)
20
Q
What is transudate?
A
Low protien condate (Specific gravity less than 1.012)
21
Q
What is edema?
A
Excess fluid in interstitial tissue or body cavities
22
Q
What is purulent exudate?
A
Exudate rich in neutrophils
23
Q
Is edema transudate or exudate?
A
Transudate
24
Q
What are the changes in pressure in transudate?
A
- increased hydrostatic pressure
2. Decreased colloid osmotic pressure
25
Main cause of transudate?
1. increased hydrostatic pressure
| 2. Decreased colloid osmotic pressure
26
Main cause of exudate?
Inflammation
27
Compare transudate and exudate in terms of appearance?
Transudate: clear
Exudate: cloudy
28
Compare transudate and exudate in terms of fluid protein?
Transudate: less than 0.5
Exudate: greater than 0.5
29
Compare transudate and exudate in terms of fluid LDH?
Transudate: Less than 0.6
Exudate: Greater than 0.6
30
What is the earliest manifestation of acute inflammation?
Vasodilation
31
Vasodilation first involves what vessels?
Arterioles through opening of new capillary beds
32
Vasodilation causes what two things? (2)
1. heat
| 2. redness
33
Vasodilation is induced by what?
| Two examples?
Mediators of vascular smooth muscle
Histamine and NO
34
Vasodilation is followed by what in acute inflammation?
Increased permeability of microvasculature
35
Changes in vascular flow and caliber lead to what? (3)
| All these combine for what state of flow?
1. slower blood flow
2. concentration of red blood cells in small vessels
3. Increased viscosity
Stasis
36
Vascular leakage is normally due to what?
What is this called normally?
If it takes too long?
Contraction of endothelial cells resulting in increased interendothelial spaces
Immediate transient response (15-30 minutes)
Delayed prolonged leakage (2-12 hours)
37
Delayed prolonged leakage is seen when ? (3)
1. burns
2. UV
3. bacterial toxins
38
Two other causes of vascular leakage?
1. endothelial injury: loss of endothelial cells
| 2. Transcytosis
39
What is transcytosis?
Increased transport of fluids and proteins through endothelial cells
40
During inflammation, what changes in lymph flow?
It is increased due to edema
41
What is lymphangitis?
Inflammation of lymphatic vessels
42
What is reactive or inflammatory lymphadenitis?
Lymph node enlargement because of hyperplasia of the lymphoid follicles and increased numbers of lymphocytes and macrophages
43
Streaking near a skin wound follows what?
| What is it diagnostic of?
Course of lymphatic channels
Diagnostic of lymphangitis
44
What is lymphadenitis?
Painful enlargement of draining lymph nodes
45
What are the four steps of recruitment of leukocytes to sites of injury and infection?
1. Margination
2. Rolling
3. adhesion
4. Diapedesis
46
In stasis, what do WBC's do?
| What is this process called?
WBC's become more peripheral along endothelial surface
| Margination
47
Rolling interactions are mediated by what proteins?
Selectins
48
What is rolling regulated by?
Cytokines
49
Selectins in leukocytes are called?
L-selectins
50
Selectins in endothelium are called what?
E-selectin
51
Selectins in platelets are called what?
P-selectin
52
Firm adhesion of leukocytes is mediated by what?
Integrins
53
What two cytokines induce endothelial expression of ligands for integrins?
TNF and IL-1
54
V-CAM is ligand for what?
VLA-4 integrin
55
ICAM1 is ligand for what?
LFA-1 and Mac-1
56
Leukocytes normally express integrins in what state?
| What reverses this?
Low affinity
| Chemokines
57
What conains P-selectin and vWF in endothelial cells and platelets?
Weibel Palade Bodies
58
What causes a cell to express P-selectin? 2
Histamine and thrombin
59
3 rolling endothelial molecules and their corresponding leukocyte molecule?
1. P-selectin: Sialyl Lewis
2. E-selectin: Sialyl Lewis
3. Glycam-1/CD34: L-selectin
60
2 adhesion endothelial molecules and corresponding leukocyte molecule?
1. ICAM-1: LFA-1, MAC-1
| 2. VCAM-1: VLA-4
61
LAD-1 is a defect in what?
| What is the functional result of this?
Defect in Beta2 chain of LFA-1 and Mac-1 integrins.
Neutrophils can't adhere
62
Clinical manifestation of LAD-1? (3)
1. Skin infections
2. Inflammatory lesions without neutrophils
3. Delayed separation of umbilical cord at birth
63
Treatment of LAD-1?
Granulocyte concentration with functional WBC's.
64
LAD-2 is a defect in what?
| What is functional result of this?
Absence of sialyl-lewis for E- and P- selectins
| Rolling issue
65
Manifestations of LAD-2? 2
Skin infections
| Mental retardation
66
Leukocyte migration across endothelial cells is called what?
Diapedesis or Transmigration
67
Where does diapedesis occur?
Post-capillary venules
68
What mediates diapedesis?
PECAM
69
What do leukocytes make to cross BM?
Collagenases
70
What is the most common exogenous agent for chemotaxis?
Bacterial products
71
endogenous chemoattracts include? 3
1. Cytokines (IL-8)
2. Components of complement (C5a and C3a)
3. Arachidonic acid metabolites (leukotrieneB4)
72
First cell on scene are what?
| Why? (2)
neutrophils
1. more present in blood
2. Respond very rapidly to chemokines
73
When do neutrophils dominate the inflammatory infiltrate?
6 to 24 hours
74
Monocytes predominate during when?
| Why? 2
24-48 hours
1. last longer
2. proliferate in tissues
75
Exceptions to when cells show up first (so not neutrophils first) 1
1. Viral infections (lymphocytes first)
| 2. Hypersensitivity (eosinophils)
76
Responses of leukocytes consist of what two sets of events?
1. Recognition of offending agents
| 2. Activation of leukocytes to ingest and destroy offending agents and amplify the inflammatory reaction
77
Leukocytes have what receptors (4)
1. Toll-like receptors
2. G-coupled receptors
3. Receptors for opsonins
4. Receptors for cytokines
78
G-protein coupled receptors recognize what?
Bacterial peptide containing N-FM residues
79
Leukocyte receptors for cytokines include what main one?
IFN-gamma (macrophage activating cytokine)
80
Three steps of phagocytosis?
1. Recognition and attachment of particle
2. Engulfment that forms a vacuole
3. Killing or degradation of material
81
Receptors for phagocytosis include? (3)
1. mannose receptors
2. scavenger receptors
3. receptors for various opsonins
82
What are the three steps of engulfment?
1. Extensions of cytoplasm (pseudopods) around material
2. Plasma membrane pinches off to form phagosome
3. phagosome fuses with lysosome to make phagolysosome
83
Microbial killing is accomplished by what? (2)
1. ROS
| 2. reactive nitrogen species
84
Substances in leukocyte granules for phagocytosis include? 7
1. elastase
2. defensins
3. cathelicidins
4. lysozyme
5. lactoferrin
6. major basic protein
7. bactericidal/permeability increasing protein
85
What is the most efficient bactericidal system in neutrophils?
H2O2-MPO halide system
86
What happens in H2O2-MPO-halide system? 3
1. H2O2 generated by NADPH
2. Myeloperoxidase in granules of PMN's converts H2O2 to hypochlorite (bleach)
3. killing by halogenation or lipid peroxidation
87
The growth factors that activated leukocytes produce do what? (3)
1. Stimulate proliferation of endothelial cells
2. promote synthesis of collagen
3. Promote enzymes that remodel CT
88
Classically activated macrophage (M1) does what?
Microbicidal
89
Alternatively activated macrophage is involved in what?
tissue repair and fibrosis
90
Do activated leukocytes secrete mediators or inhibitors of inflammatory response?
Both
91
What are 3 situations in which leukocytes mediate tissue injury?
1. Infection
2. Autoimmune
3. React excessively against environmental substances
92
What is frustrated phagocytosis
Inability of leukocytes to surround and ingest activating substances with release of lysosomal enzymes extracellularly
93
4 defects in leukocyte function
1. leukocyte adhesion defect
2. phagolysosome defect
3. microbicidal activity defect
4. acquired deficiencies
94
The main leukocyte adhesion defect is what?
Clinical problem?
Classic example?
LAD1 and LAD2
recurrent bacterial infections
delayed umbilical cord separation
95
What is main disease of phagolysosome function?
Chediak-Higashi syndrome
96
Manifestations of Chediak-Higashi syndrome?
1. Albinism (melanocyte problem)
2. nerve defects
3. bleeding
4. Defective PMN's
5. Leukocytes with giant granules
6. Delayed killing
97
What is the genetic problem in chediak-higashi?
LYST gene
98
What is the main defect in microbicidal activity in leukocytes?
Chronic granulomatous disease
99
Chronic granulomatous disease is result of what mutation?
Defective genes encoding NADPH-oxidase either X-linked or autosomal recessive
100
The variants of chronic granulomatous disease also differ in terms of location, what are they?
1. X-linked: membrane
| 2. AR: cytosol
101
Patients with granulomatous disease have what problem?
Recurrent bacterial infection (catalase positive)
102
Test for chronic granulomatouse disease is what?
Nitroblue tetrazolium (yellow = disease)
103
Most frequent cause of leukocyte defects is what?
Bone marrow suppression due to diabetes or steroids
104
Mediators of inflammation are made when?
Long as the stimulus persists (rapid bursts)
105
What are the anti-inflammatory cytokines? (2)
1. TGF-beta
| 2. IL-10
106
What are the anti-inflammatory lipid mediators called? (2)
1. Resolvins
| 2. protectins
107
What neural impulse inhibits production of TNF in macrophages?
Cholinergic discharge
108
Mediators are generated from what?
Cells or plasma proteins
109
What is the relative length of life of a mediator of inflammation?
Short
110
What are the two major vasoactive amines?
Histamine
| Serotonin
111
When are vasoactive amines released?
First to be released during inflammation
112
Histamine is released by what cells? (3)
1. mast cells
2. basophils
3. platelets
113
Histamine is released to what stimuli? 6
1. Physical injury
2. binding of antibodies to mast cell
3. anaphylatoxins (c3a c5a)
4. histamine-releasing proteins from leukocytes
5. neuropeptides
6. Cytokines (IL-1, IL8)
114
What neuropeptide modulates pain?
Substance P
115
Histamine causes what? 2
Arterior dilation
| Increases permeability of venules
116
Histamine is the principal mediator of what?
Immediate phase of increased vascular pemerability
117
Where does histamine bind?
H1 receptors in interendothelial gaps of venules
118
Serotonin has what effects? 2
Arterior dilation
| Increases permeability of venules
119
Serotonin is found where?
| When is it released?
Platelets
Platelet aggregation
120
What cells have serotonin in GI?
Enterochromaffin
121
Membrane derived arachidonic acid produces what?
Via what enzyme?
What initiates all this?
Prostaglandins and leukotrienes
Phospholipases
inflammatory mediators
122
Steroids have what effects on phospholipases?
Inhibit them.
123
COX converts what to what?
Arachidonic acid into prostaglandins, prostacyclin, and thromboxanes.
124
12-lipoxygenase converts what to what?
5-HPETE into lipoxin
125
Prostacyclin causes what? 2
Vasodilation
| Inhibits platelet aggregation
126
Thrombaxane A2 causes what? 2
Causes vasoconstriction
| Promotes platelet aggregation
127
PGD2 and PGE2 causes what? 2
Vasodilation
| Increased vascular permeability
128
Leukotrienes do what? 3
Vasoconstriction
Bronchospasm
Increased vascular permeability
129
Lipoxins do what? 2
Inhibit neutrophil adhesion and chemotaxis
130
5-lipoxygenase converts what to what?
Arachidonic acid into leukotriene and lipoxin
131
Platelets contain what prostaglandin enzyme?
| Which makes what?
Thromboxane synthetase
| TxA2
132
What prostglandin enzyme does vascular endothelium have?
Prostacyclin synthetase
133
Aspirin and NSAIDS inhibit what enzymes?
COX-1 and COX-2
134
COX-2 generates prostaglandins involved in what reactions?
Inflammatory reactions
135
COX-1 generates prostaglandins involved in what?
Cytoprotective and inflammatory reactions
136
LTB4 causes what?
Neutrophils to aggregate (chemotactic)
137
LTC4, LTD4, LTE4 cause what? (3)
Vasoconstriction
Bronchospasm
Increased vascular permeability
138
Which is more potent, leukotrienes or histamine?
Leukotrienes
139
Lipoxin LxA4 causes what?
1. vasodilation
| 2. antagonizes LTC4
140
Lipoxins may have what relationship with leukotrienes?
Negative regulators of leukotriene actions
141
What are the two COX inhibitors?
ASA and NSAIDS
142
What are the two lipoxygenase inhibitors?
Zileuton
| Montelukast
143
Montelukast is used in treatment of what?
Asthma
144
Fish oil has what effect on eicosanoids synthesis? 2
Fish oils can be poorly converted into active metabolites by COX and LOX pathways.
Can be used to produce resolvins and protectins
145
Platelet activating factor is generated from what?
Membrane phospholipids
146
What does PAF do? 7
1. leukocyte adhesion
2. chemotaxis
3. degranulation
4. oxidative burst
5. vasoconstriction
6. bronchoconstriction
7. increased vascular permeability
147
Free radicals at low levels do what?
Increase cytokines
148
Free radicals at high levels do what? (2)
1. tissue damage
| 2. inactivate antiproteases
149
Antioxidant protective mechanisms are include what? 5
1. catalase
2. superoxide dismutase
3. glutathione peroxidase
4. ceruloplasmin
5. transferrin
150
Nitric oxide factor is released from what cells?
| Causes what?
Endothelial cells
Relax smooth muscle causing vasodilation
151
NO in macrophages does what?
kills microbes
152
What is NO's role in inflammation? 3
1. vasodilation
2. antagonize platelet aggregation and adhesion
3. Microbicidal agent
153
Cytokines are defined how?
Peptides modulating functions of other cells
154
TNF and IL-1 are produced by what cells?
Activated macrophages
155
TNF and IL-1 have what effects? 2
1. cause endothelial activation
| 2. Induce acute phase responses
156
Production of IL-1 is called what?
Inflammasome
157
What happens when IL-1 is mutated?
Cause inherited autoinflammatory syndromes (familial Mediterranean fever) (upregulated IL-1 production
158
Sustained release of TNF causes what?
Cachexia
159
C-X-C chemokines use what coreceptor for HIV?
CXCR4
160
C-C chemokines use what coreceptor for HIV?
CCR5
161
What is the main C chemokine (gamma chemokine)
Lymphotactin
162
What is the main CX3C chemokine?
Fractalkine
163
Two main functions of chemokines?
1. Recruit leukocytes
| 2. Control normal migration of cell through tissues
164
IFN-gamma is released by what cells?
T lymphocytes and NK cells
165
IFN-gamma activates what?
Macrophages
166
What counteracts proteases?
| Two examples?
Antiproteases
1. alpha2-macroglobulin
2. alpha1-antitrypsin
167
Neuropeptides are secreted by who?
Sensory nerve fibers and leukocytes
168
Neuropeptides have what role?
Initiate and propagate inflammatory response
169
Nerve fibers containing substance P do what? (3)
1. transmit pain signals
2. regulate vessel tone
3. modulate vascular permeability
170
Is complement system innate or adaptive?
Both
171
What triggers classical complement pathway?
Fixation of C1 to IgM or IgG
172
What triggers alternative pathway?
Microbial surface proteins
173
C3a and C5a are called?
| Because they do what?
Anaphylatoxins
| Stimulate histamine release
174
c5a acts as what agent as well?
| What can it activate also?
Chemotactic for leukocytes
| Activate lipoxygenase pathway
175
C3b has what role in phagocytosis?
Act as opsonin
176
MAC makes cells permeable to what?
Water and ions
177
Intrinsic clotting pathway activated by what?
Hageman factor/Factor XII
178
Thrombin promotes what?
Inflammation
179
Describe the steps of Kinin system 2
1. Factor XIIa converts prekallikrein into kallikrein
| 2. Kallikrein converts HMWK into bradykinin
180
What are the precursors of vasoactive peptides called?
Kininogens
181
Bradykinin has what functions? (3)
1. Increase vascular permeability
2. Smooth muscle contraction
3. Dilation of blood vessels
182
What inactivates bradykinin?
Kininase
183
Factor XIIa, induces what two pathways?
1. fibrin clot formation
| 2. fibrinolytic system
184
What other thing does kallikrein do besides kinin pathway? 2
Converts plasminogen to plasmin
| Convert C5 to C5a
185
Activated Hageman factor (factor XIIa) initiates what four pathways?
Kinin
Clotting
Fibrinolytic
Complement
186
What does plasmin do?
1. Cleaves fibrin
| 2. Converts C3 to C3a
187
What are possible outcomes of inflammation? (2)
1. Resolution and healing
| 2. progression to chronic inflammation
188
Morphologic hallmarks of inflammation? (3)
1. Dilation of small blood vessels
2. slowing of blood flow
3. accumulation of leukocytes and fluid in extravascular tissue
189
What is serous inflammation?
| Example?
Outpouring of thin fluid (effusion)
Skin blister
190
What is fibrinous inflammation?
| When is it seen?
Fibrin is formed and deposited in extracellular spaces. Exudate develops when leaks become large.
Common in lining of body cavities: meninges, pericardium, pleura
191
Suppurative/purulent inflammation/abscess is due to what?
Production of large amounts of pus or purulent exudate.
192
bacteria that cause pus formation are known as what?
Pyogenic
193
What is an ulcer?
Local defect on surface of organ or tissue produced by sloughing or inflamed necrotic tissue
194
What is chronic inflammation?
Inflammation lasting weeks to months
195
Chronic inflammation results from what? (3)
1. persistent microbial infections
2. prolonged exposure to toxic agents
3. autoimmune diseases
196
Silica in lungs leads to what?
Silicosis
197
Plasma lipid toxicity is known as what?
Atherosclerosis
198
Characteristic cells of chronic inflammation?
Macrophages
Lymphocytes
Plasma cells
199
What shows up morphologically in chronic inflammation?
Tissue destruction
| Attempts to heal by CT replacement of damaged tissue utilizing angiogenesis and fibrosis
200
What is the dominant player in chronic inflammation?
Macrophages
201
Macrophages in spleen and lymph nodes are known as what?
Sinus histiocytes
202
macrophages in placenta?
Hofbauer cell
203
Half life of blood monocyte?
1 day
204
life span of tissue macrophage?
several months or years
205
Macrophages secrete products to do what?
1. eliminate agents (ROS, NO, enzymes)
| 2. initiate repair (growth factors)
206
Plasma cells are involved in opsonization how?
Make IgG
207
granules of eosinophils contain what?
Major basic protein
208
Mast cells are found in what tissues mainly?
CT
209
Mast cells upon IgE activation do what?
Release histamines and prostaglandins
210
What is chronic bacterial infection of bone?
Osteomyelitis
211
What are two types of granulomas?
Foreign body
| Immune granulomas
212
What initiates a foreign body granuloma?
Inert foreign bodies like sutures
213
What initiates immune granulomas?
| Typical one
Something doesn't degrade well.
| Myobacterium tuberculosis
214
What does defective inflammation result in?
| Why?
Susceptibility to infections
And bad wound healing
Bad inflammation = bad innate immunity
