Inflammation and Repair Flashcards
1
Q
Eosinophils are abundant in what types of reactions?
A
Those mediated by IgE
Parasitic infections
2
Q
The increase in vascular permeability is seen in what type of vasculature?
A
postcapillary venules!!
3
Q
Which of the cyclooxygenase enzymes are present in both normal tissues and in response to inflammatory stimuli?
A
COX-1
4
Q
What do M2 macrophages produce that assist in tissue repair?
A
Growth factors
TGF-β
5
Q
5-lipoxygenase generates what lipid mediator?
A
Leukotrienes
6
Q
What cells are the most important in inflammatory reactions?
A
cells that phagocytose: macrophages and neutrophils
7
Q
Overall function of the leukotriene mediators?
A
Increased vascular permeability, chemotaxis, leukocyte adhesion and activation
8
Q
Why is pus considered an exudate?
A
it contains leukocytes (mainly neutrophils), cellular debris and microbes
9
Q
Keloid scar formation is more common in what population of individuals?
A
African Americans
10
Q
What prostaglandin is responsible for pathogeneis of pain and fever during inflammatory response?
A
PGE2
11
Q
inflammation associated with cytokine-induced systemic reactions are referred to as?
A
acute-phase response
12
Q
What type of macrophage arises from the classical pathway of activation?
What cytokines are involved?
A
An M1 macrophage
microbes, INF-γ
13
Q
What type of macrophage arises from the alternative pathway?
What cytokines are involved?
A
M2 macrophage
IL-13 and IL-4
14
Q
What other mediator has actions similar to histamine, with the function of increasing vascular permeability, contraction of smooth muscle, dilation of blood vessels and pain when injected into the skin?
A
Bradykinin
15
Q
In granulomas, what contributes to the formation of the central zone of necrosis?
A
Hypoxia and free-radical mediate injury
16
Q
Liver macrophages
A
Kupffer cells
17
Q
Deficiency in C1 inhibitor leads to what condition?
A
Hereditary angioedema
18
Q
What other function does C5a have, besides stimulation of histamine release?
A
C5a is a chemotatic agent
C5a also activates the lipoxygenase pathway, causing further release of inflammatory mediators
19
Q
What leukocyte prodominates in the first 24 hours of inflammation?
A
Neutrophils
20
Q
What is the complement system?
A
A collection of soluble proteins and membrane receptors that function in host defence against microbes and pathologic inflammatory rxns
21
Q
Leukocytosis is typically induced by what sort of infections?
A
Bacterial
22
Q
TH17 cells secrete what cytokine and what is its function?
A
IL-17
induce the secretion of chemokines responsible for recruiting neutrophils and monocytes to the site of inflammation
23
Q
What lymphocyte secretes cytokine and thus promotes inflammation?
A
CD4+ T-cells
24
Q
The cytokines responsible for leukocyte adhesion and migration are?
A
TNF and IL-1
25
Acute inflammation occurs in response to what circumstances?
Infection, necrosis
26
Immune response cells involved in chronic arthritis?
lymphocytes, macrophages
27
If fibrosis occurs in a space occupied by an exudate it is termed
Organization
28
The M1 macrophage produce what mediators that contribute to inflammation?
IL-1, IL-12, IL-23 and chemokines
29
What cells produce the mediators of CT deposition?
Primarily M2 macrophages; mast cells and lymphocytes may be present and produce them as well
30
Why is aspirin used to bring down fevers?
ASA inhibits cyclooxygenase, therefore preventing the production of prostaglandins
31
what other molecules are generated from arachidonic acid by lipoxygenase, but function as anti-inflammatory agents?
Lipoxins (LXA4 and LXB4)
32
What anti-inflammatory mediators are involved in termination of the acute inflammatory response?
TGF-β and IL-10
33
What pathway ensures that new blood vessels have proper spacing to effectively supply healing tissue with blood?
Notch signaling pathway
34
What is the mechanism behind leukocyte-dependent tissue injury?
When a leukocyte is activated, their effector mechanisms do not distinguish between host and offender, leading to damage of normal cells and tissues in addition to a microbe
35
Why do macrophage mannose binding receptors only bind microbes and not host cells?
These receptors bind terminal mannose and fructose residues of microbial glycoproteins and glycolipids rather than terminal sialic acid or N-acetylgalactosamine
36
What are the cardinal signs of inflammation?
Rubor (redness)
Tumor (swelling)
Calor (warmth)
Dolor (pain)
Functio laesa (loss of function)
37
What is the downside to using TNF antagonists as a treatment for chronic inflammatory diseases?
Patients become more susceptible to mycobacterial infections, with a reduced ability to kill intracellular microbes
38
Degradation of collagen and other ECM components involved in deposition of connective tissue is accomplished by what enzymes?
What do these enzymes depend on for their activity?
Matrix metalloproteinases (MMPs)
Metal ions
39
Wound dehiscence and ulcerations occur as a result of
inadequate formation of a scar or granulation tissue
40
Components of exudate?
Extravascular fluid with high protein concentration and cellular debris
41
What is the primary response cell in pseudomonas bacterial infections?
Neutrophils
42
Acute inflammatory reactions have 3 possible outcomes:
1. Complete resolution
2. healing by CT replacement (scarring)
3. Progression to chronic inflammation
43
Of the factors that influence tissue repair, what is the most common systemic cause of abnormal wound healing
Diabetes Mellitus
44
Under what circumstances would a wound heal by first intention?
When the injury involves only the epithelial layer
45
Lung macrophages
alveolar macrophages
46
Antagonists to what cytokine have been shown to be an effective tx for chronic inflammatory diseases?
TNF
47
What are the types of selectins that are involved in leukocyte rolling?
L-selectin on leukocytes
E-selectin on endothelium
P-selectin on platelets and endothelium
48
What are the three pathways of complement?
Classic pathway
Alternative pathway
Lectin pathway
49
Immune cells involved in pulmonary fibrosis?
macrophages and fibroblasts
50
Which of the neutrophil granule types contains myeloperoxidase?
Azurophilic granules
51
Of the factors the influence tissue repair, which is the most clinically important delay of healing?
infection
52
What drives the regeneration of tissues and injured cells?
Growth factors
53
What is the result of vasodilation?
Increased blood flow, leading to erythema at the site of infection
54
Lymphangitis
Inflammation of the lymphatics, often leaves a red streak to the site of lymph nodes as the lymph fluid brings infection with it.
55
Repair begins 24 hours after injury with the emigration and induction of proliferation of what cell types?
fibroblasts and endothelial cells
56
The selectin ligands are what type of molecules?
sialylated oligosaccharides bound to mucin-like glycoprotein backbones
57
Steps involved in deposition of CT
Migration and proliferation of fibroblasts to site of injury
Deposition of ECM proteins produced by fibroblasts
58
Overall action of prostaglandins?
Vasodilation, pain, fever
59
What effects does hepcidin have during the acute-phase reaction?
Elevated levels of hepcidin reduce the availability of iron, leading to the anemia often seen with chronic inflammation
60
Normal differental count of eosinophils in WBC count?
1-4%
61
During the growth factor phase of liver regneration, cells release what GFs to act on hepatocytes, triggering them to move from G0 phase into the G1 phase of the cell cycle?
HGF and TGF-α
62
What are the important mediators of the acute-phase response
IL-1
TNF
IL-6
63
What is the most common mechanism of vascular leakage and what mediators elicit this response?
contraction of endothelial cells leading to an increase in space of the tight junctions
mediated by histamine, bradykinin, and leukotrienes
64
TNF causes what pathologic effects in the heart?
decreased cardiac output
65
Under what circumstances would a wound heal by second intention?
when cell or tissue loss is more extensive, as seen in large wounds, abscesses, ulcerations and ischemic necrosis
66
What is the most common cause of chronic inflammation?
Persistent infection that cannot be cleared by an acute inflammatory response
67
What is typically used to treat autoinflammatory syndromes?
IL-1 antagonists
68
LTC4, LTD4, and LTE4 are cysteinyl-containing leukotrienes that are responsible for?
Causing intense vasoconstriction, bronchospasms, and increased permeability of the venules
69
C3b is an opsonin, what is the purpose of an opsonin?
Opsonins promote phagocytosis by making the microbe "tastier" to phagocytes
70
Acute inflammation has three major components:
1. dilation of small blood vessels to increase blood flow
2. Increased permeability of vasculature to allow for plasma proteins and leukocytes to leave circulation
3. Migration of the leukocytes to site of injury
71
Activation of complement is controlled by which regulatory proteins?
C1 inhibitor
Decay accelerating factor
CD59
72
The presence of transudate indicates what?
There has been an osmotic or hydrostatic imbalance across a vessel wall **without** an increase in permeability
73
Tissue repair via regeneration occurs how?
Proliferation of residual cells
Maturation of stem cells
74
What is the main response cell in viral infections?
Lymphocytes
75
Function of M2 macrophages
Tissue repair
76
Normal differental count of neutrophils in WBC count?
40-70%
77
What happens when an infection causes an inflammatory response that is systemic, rather than local, causing widespread pathologic abnormalities?
Sepsis
78
When does fibrinous inflammation develop?
When vascular permeability allows large molecules like fibrin to pass out of the blood
79
As stasis develops, what do blood leukocytes do?
They accumulate along the vascular endothelium to then eventually migrate through and out to the tissues.
80
in the process of NET formation, neutrophils lose their nuclei, ultimately lead to
death of the neutrophil
81
Granulomatous inflammation is a form of chronic inflammation characterized by
collections of activated macrophages, often with T-lymphocytes and sometimes associated with a central region of necrosis
82
How do giant cells form?
What cytokine induces the formation?
Fusion of multiple activated macrophages
INF-γ
83
What is characteristic of an immune granuloma?
They care caused by agents that induce a persistent T-cell mediated immune response
84
What event follows vasodilation in an acute inflammatory response
increased permeability of the mnicrovasculature, leading to leakage of protein-rich fluid into extravascular tissue (exudate)
85
Mediators of acute inflammation include:
Toll-like receptors
Arachadonic acid metabolites
Mast cells
Complement
86
Angiogenesis is the process of developing new blood vessels and is critical in healing, these new vessels are leaky d/t the effects of what growth factor?
Vascular endothelial growth factor (VGEF)
87
Principal mediators of vasodilation?
Histamine
Prostaglandins
88
Hematopoietic cells, surface epithelium, columnar epithelium of the GI tract, uterus and uterine tubes, transitional epithelium of the urinary tract are considered to be labile tissues because of what characteristic?
They are continuously being lost and replaced by the maturation of tissue stem cells and proliferation of mature cells.
89
What enzyme is responsible for creating superoxide anion during the respiratory burst?
NADPH oxidase
90
What circulating protein recognizes microbial sugars and activates the complement system in order to produce mediators of inflammation?
Mannose-binding lectin
91
TH2 cells produce what cytokines and what are their functions?
IL-4, IL-5, IL-13
Recruit and activate eosinophils, promote class switching to IgE, activation of M2 macrophages
92
Through what types of reactions does tissue repair occur?
Regeneration
Deposition of CT to form a scar
93
What leukotriene is a potent chemotactic agent for neutrophils?
LTB4
94
Elevated levels of CRP in serum can be indicative of?
increased risk of MI
95
Principal mediators of increased vascular permeability
Histamine
5HT
C3a and C5a
LTC4, LTD4, LTE4
96
what are the major participants in an inflammatory reaction?
blood vessels and leukocytes
97
Monocytes migrate to various tissues where they then differentiate into macrophages, what two pathways give rise to macrophages?
Classical pathway
Alternative pathway
98
What growth factors are involved in the structural maturation of newly formed blood vessels?
Angiopoietin 1 and 2
99
When would tissue repair by CT deposition occur?
When tissues are incapable of completely healing by regeneration
100
Erythrocyte sedimentary rate (ESR) is often measured to test for an inflammatory response, what is the mechanism behind this?
Fibrinogen, an acute-phase protein, binds to RBCs, causing them to form stacks (rouleaux) that sediment more rapidly than an individual RBC
101
Tissue macrophages, mast cells and endothelial cells that encounter microbes and dead tissue respond by secreting cytokines that induce expression of adhesion molecules, what are these cytokines?
TNF (tumor necrosis factor) and IL-1
102
Leukocytes transmigrate through interendothelial spaces toward the site of infection with the help of what adhesion molecules?
CD31 or PECAM-1
103
Macrophages are tissue cells, when they are circulating in blood they are referred to as?
Monocytes
104
TNF and IL-1 produce what pathologic effect in skeletal M?
Increased insulin resistence
105
What is the function of Decay Accelerating Factor?
Prevents the formation of C3 convertase
106
Steps involved in phagocytosis
1. Recognition and attachment
2. Engulfment
3. Killing and degradation
107
For what reason is tissue destruction a hallmark of chronic inflammation?
Certain activities of macrophages promote inflammation and tissue damage
108
Killing of microbes is accomplished via
ROS and NO
109
What lipid mediator is responsible for vasoconstriction and platelet aggregation
Thromboxane A2
110
For what reasons are neutrophils the predominate responder?
There are more of them in the blood, they respond rapidly to chemokines, they attach more firmly to cell adhesion molecules (P and E selectins)
111
Once a microbe has bound to a phagocytic receptor, it undergoes engulfment. What are the steps?
The plasma membrane extends pseudopods around the microbe, forming a vesicle around it (phagosome)
The phagosome then fuses with a lysosome to form a phagolysosome
112
What is more potent for causing vascular permeability and bronchospasm (histamine or leukotriene)?
Leukotrienes
113
What cytokine is involved in the first priming phase of liver regeneration?
What cells produce this cytokine?
IL-6 produced by Kupffer cells
114
Wound contraction occurs with the help of what cell type?
myofibroblasts
115
Deficiency in DAF and CD59 lead to what disease?
Paroxysmal nocturnal hemoglobinuria (PNH)
116
What causes neutrophilia?
A bacterial infection that increases the number of neutrophils in the blood count
117
How are prostaglandins produced in order to cause an increase in body temperature?
Bacterial LPS stimulate leukocytes to release IL-1 and TNF
IL-1 and TNF stimulate cyclooxygenase, which converts arachidonic acid into prostaglandins
118
What is the role of PDGF growth factor in angiogenesis?
Recruits smooth muscle cells
119
Exogenous pyrogens involved in the acute phase response
LPS, which activates IL-1 and TNF (endogenous pyrogens)
120
What types of phagocytic disorders are considered to be intrinsic?
Chronic granulomatous disease
Glycogen storage disease
Chediak-Higashi syndrome
121
How are arachidonic acids released from membrane phospholipids?
through the cellular action of phospholipases, specficially phospholipase A2
122
What cytokines are responsible for induction of fever?
IL-1 and TNF
123
If a granuloma does not have a central zone of necrosis, what type of granuloma is it?
Non-caseating
124
Autoinflammatory syndromes are caused by what type of mutation?
Gain of function mutations in the sensors that detect infection
125
What is a common example of purulent inflammation?
acute appendicitis
126
Phospholipase A2 is inhibited by __ preventing the production of arachidonic acid
Steroids
127
What is the role of TGF-β in angiogenesis?
supresses the proliferation and migration of endothelial cells, rather enhancing the ECM protein production
128
M1 macrophages produce what substances that contribute to phagocytosis?
ROS, NO, lysosomal enzymes
129
What is the most common exogenous chemotactic substance, attracting leukocytes to the site of inflammation?
Bacterial products
130
131
What is a leukemoid reaction?
Extreme elevations in WBC count (40k-100k) 2/2 infection, similar to counts seen in patients with leukemia
132
In the termination phase of liver regeneration, cells return to G0 phase of the cell cycle with the help of what cytokine?
TGF-β
133
Proud flesh results from the formation of excessive amounts of granulation tissue, which often requires removal by cautery or surgical excision.
The exuberant proliferation of fibroblasts that occurs after excision leads to?
Formation of desmoids or aggressive firbromatoses
These are low-grade neoplasms (between benign and malignant)
134
The ability of a tissue to repair is determined by what factor?
Their intrinsic proliferative capacity
135
What molecules are capable of inhibiting cyclooxygenase and therefor prevent the production of prostaglandins?
COX-1 and COx-2 inhibitors, aspirin, indomethacin
136
What mechanisms are in place to protect against oxygen-derived radicals that are released from leukocytes after exposure to microbes?
Superoxide dismutase
catalase
glutathione peroxidase
ceruloplasm
transferrin
137
What are the main characteristics of an acute inflammatory response?
Edema
Migration of Neutrophils to site of infection
138
Cells primarily invloved in ARDS?
Neutrophils
139
Toxic granulations are common in patients with what condition?
Sepsis
140
NO is produced by NOS and contributes to microbial killing, of the types of NOS, which does?
iNOS (inducible)
141
Inflammatory response cells involved in both acute and chronic asthma?
IgE and Eosinophils
142
What causes the decrease in blood flow during an acute inflammatory reaction?
The increased permeability and exudation of high protein fluid following vasodilation
143
Parenchymal organs have limited regeneration capabilities except for which organ?
Liver
144
What enzyme converts arachadonic acid into leukotrienes?
5-Lipoxygenase
145
Cyclooxygenase produces what type of lipid mediator?
What specific subtypes of this enzyme?
Prostaglandins
COX-1 and COX-2
146
What is the ligand for the integrin VLA-4?
VCAM-1
147
What differentiates chronic inflammation from acute inflammation?
Chronic inflammation is a delayed response and is also more specific d/t adaptive immunity
148
What induces a left shift in leukocytosis?
the initial accelerated release of cells from the bone marrow caused by TNF and IL-1 leads to an increase in the number of immature neutrophils in the blood
149
What are the major opsonins?
IgG, C3b, and mannose-binding lectin
150
What is the predominant lipoxygenase in neutrophils?
5-lipoxygenase
151
M1 macrophages produce what factors that contribute to inflammation?
IL-1
IL-12
IL-23
Chemokines
152
Since H2O2 is not sufficient in killing microbes, it is converted into hypochlorite using what enzyme?
Where is this enzyme found?
Myeloperoxidase (MPO)
Within azurophilic granules of neutrophils
153
What are the hallmarks of chronic inflammation?
presence of macrophages, lymphocytes and plasma cells
154
What is the major factor involved in formation of tissue fibrosis?
TGF-β
155
Steps involved in angiogenesis:
1. Vasodilation in response to NO and increased permeability of existing blood vessel induced by VGEF
2. Breakdown of the basement membrane to allow sprouting of new vessel
3. Migration of endothelial cells to site of injury
4. Endothelial cell proliferation
5. Remodeling into capillary tubules
6. Recruitment of periendothelial cells to form a mature vessel
7. suppression of endothelial proliferation, migration and deposition
156
Bradykinin is generated via cleavage of Kininogen by what enzyme?
Kallikrein
157
In what type of leukocyte are toxic granulations found?
Neutrophils
158
what is the most common cause of defective inflammation\<
Leukocyte deficiency
159
Principal mediators of pain
Prostaglandins
Bradykinin
160
what growth factor stimulates the proliferation of hematopoietic stem cells in response to loss of blood cells?
Colony-stimulating factor (CSF)
161
What types of phagocytic defects are considered to be extrinsic?
abnormalities in opsonization 2/2 deficiencies of Ab and complement factors
162
What lipid mediator is responsible for vasodilation and inhibition of platelet aggregation?
Prostacyclin, aka PGI2
163
B and T lymphocytes contribute to chronic inflammation how?
They are activated by microbes and other environmental agents, which then amplifies and propagates the chronic inflammatory response
164
what factors influence the outcome of tissue repair?
the balance between synthesis and degradation of ECM proteins
165
What is characteristic of foreign body granulomas?
They do not elicit an inflammatory or immune response
166
Morphologic patterns of acute inflammation include?
Serous inflammation
Fibrinous inflammation
Purulent (suppurative) inflammation
Ulcers
167
What is the purpose of the vascular reactions of acute inflammation?
To maxinmize the movement of proteins and leukocytes out of circulation and to the site of injury.
168
Skin macrophages
Langerhans cells
169
NETs are produced by what leukocyte?
Neutrophil
170
What is the purpose of granuloma formation?
Attempt to contain the offending agent that is difficult to eradicate
171
Leukopenia refers to?
A decrease in the number of circulating white cells in response to certain infections
172
In what circumstance would a foreign body granuloma form?
Sutures, Talc
173
What type of mediators are sequestered in intracellular granules to be released or synthesized de novo?
Cell-derived mediators
174
Autoimmune and allergic reactions are often associated with chronic inflammation and are induced by what type of immune cells?
Cytokines produced by T lymphocytes
175
What are the sentinel cells that are responsible for producing mediators of acute inflammation?
Macrophages
Dendritic cells
Mast cells
176
what molecules are involved in leukocyte rolling and adhesion?
Selectins and integrins
177
Normal differental count of monocytes in WBC count?
4-8%
178
What growth factor stimulates receptors to induce transcytosis?
VEGF: vascular endothelial growth factor
179
What are some examples of diseases with associated granulomatous inflammation?
TB
Leprosy
Cat scratch dz
Sarcoidosis
Chrons dz
180
What cells dominate in prolonged inflammatory reactions and why?
Monocytes
Have a longer lifespan and can proliferate within tissue
181
What is the cause of septic shock?
Severe bacterial infections release large amounts of cytokines (IL-1 and TNF), which leads to disseminated intravascular coagulation, hypotensive shock and metabolic disturbances
182
What is the function of CRP and SAA in the acute phase response?
Bind to cell walls and act as opsonins, fix complement, and bind to chromatin
183
When a mediator is triggered by microbes, necrotic tissue, or hypoxia, what happens?
Mediators initiate and amplify the inflammatory response; they determine the pattern, severity, and clinical/pathological manifestations of the response
184
What are the types of granulomas?
Foreign body
immune
185
There are more than 20 proteins in the complement system, circulating in their ___ form in plasma
inactive
186
Arachidonic derived mediators are generated through two enzymes, what are they?
cyclooxygenase and 5-lipoxygenase
187
Inflammatory reactions are stimulated by what sort of stimuli?
Infections
Tissue necrosis
Foreign bodies
Immune reactions
188
What leads to the formation of a hypertrophic scar? When would this be referred to as a keloid?
When there is an accumulation of excessive amounts of collagen localized to the wound
When scar tissue grows beyond its boundaries of the original wound
189
What is one of the earliest manifestations of acute inflammation and what is it mediated by?
Vasodilation, mediated by several things but most notably **histamine**
190
Phagocytic disorders can be divided into two groups based on their defects, what are these groups?
Intrinsic
Extrinsic
191
Wound dehiscence occurs most frequently after?
abdominal surgery 2/2 increased abdominal pressure
192
Why are eosinophils helpful and why are the damaging?
Eosinophils contain granules full of *major basic protein*, which is toxic to parasites but it causes lysis of mammalian epithelial cells
193
What causes margination of leukocytes?
The stasis that occurs in the acute inflammatory response leads to hemodynamic changes that allow for the white cells to assume an peripheral position
194
What inhibits leukotriene C4, D4 and E4 and therefore inhibits bronchospasms?
leukotriene receptor antagonists
195
Exogenous pyrogen involved in fever production during the acute phase response
LPS
196
What are the NETs made of?
a viscous meshwork of nuclear chromtin that binds and concentrates granule proteins
197
Principal mediators in fever
IL-1
TNF
Prostaglandins (PGE2 specficially)
198
What is the critical step in complement activation?
Cleavage of the C3 component
Can occur via one of three pathways
199
What is the underlying function of mediators of inflammation?
inititate and regulate inflammatory response
200
What stimulates the bone marrow to produce leukocytes?
IL-1, IL-6 and TNF
201
What type of response is inflammation?
A protective response of vascular tissues
202
What is the dominant cell type in most chronic inflammatory reactions?
Macrophages
203
What are the steps encountered during a typical inflammatory reaction?
1. The offending agent, located in extravascular tissues, is **recognized**
2. Leukocytes and plasma proteins are **recruited** from circulation to the site of infection
3. leukocytes and proteins are activated to **remove** the offending agent
4. Reaction is controlled (**regulated**) and terminated
5. The damaged tissue is **repaired**
204
Why does acute inflammation have limited specificity?
Acute inflammation is an innate immune response
205
What are the morphological hallmarks of acute inflammation?
dilation of small blood vessels
accumulation of leukocytes in extravascular tissues, specifically neutrophils
206
What is the function of a neutrophil extracellular trap (NET)?
Provide a high concentraion of antimicrobial substances at sites of infection and prevent the spread of infection by trapping them in fibrils
207
What is the function of CD59 in complement regulation?
inhibts formation of the membrane attack complex
208
What protein is a chemotactic agent for neutrophils?
C5a
209
What would cause a wound to ulcerate?
Inadequate vascularization during healing
210
What is the most effective way to destroy phagocytosed material?
O2-dependent killing
211
Ulcers commonly form where?
In the mucosa of the mouth, stomach, GU tract OR skin and subcutaneous tissue of the LE in older adults/adults with circulatory disturbances (DM)
212
Changes in granulocytes visible in blood smears of patients with inflammatory conditions is known as?
Toxic granulations
213
What mediators are responsible for vasodilation and increased vascular permeability of postcapillary venules?
PGD2 and PGE2
214
Normal differental count of lymphocytes in WBC count?
20-40%
215
What is the effect of macrophages and lymphocytes interacting with one another?
Macrophages present Ags to T-cells, which produce cytokines that induce a T-cell response
T-cell cytokines recruit macrophages, promoting more Ag presentation and cytokine secretion
Chronic inflammation is sustained
216
Cell lysis via the MAC complex is the primary pathway for ridding what bacteria?
Neisseria
217
What are the most important mediators of acute inflammation?
Vasoactive amines
Lipid products (prostaglandins and leukotrienes)
Cytokines
Complement
218
Fluid located in the interstitial tissue or serous cavities, that can be either exudate or transudate is?
Edema
219
What is the mechanism behind acute on chronic inflammation?
Neutrophils are induced by persistent microbes or mediates produced by activated macrophages and T-lymphocytes
220
When would it be common to see eosinophilia?
Allergic reactions
Parasitic infections
221
What are the 3 subsets of CD4+ T-cells
TH1
TH2
TH17
222
What enzyme generates the lipoxins, A and B, which function in inhibiting inflammation?
12-lipoxygenase
223
Normal differental count of basophils in WBC count?
0-1%
224
Immune cells involved in atherosclerosis?
macrophages, lymphocytes
225
What type of mediators are produced in the liver and present in their inactive form within circulation?
Plasma-derived mediators
226
Morphology of chronic inflammation
Infiltration of mononuclear cells (macrophages, lymphocytes, plasma cells)
Tissue destruction
Attempt at healing (angiogenesis, scarring)
227
Efficiency of phagocytosis is ehanced when microbes are
opsonized
228
what growth factor is involved in proliferation of endothelial cells?
FGF-2
229
What allows for the conversion of low affinity integrins on leukocyes to high affinity integrins in order to promote firm adhesion?
Production of TNF and IL-1 at the site of injury followed by expression in high concentrations on the endothelial cells for which leukocytes roll by
230
Acute to chronic transition occurs when?
when the acute inflammatory response cannot be resolved d/t persistence of the injurious agent or some interference with the normal processes of healing
231
Resolution of an acute inflammatory reaction involves what?
removal of cellular debris and microbes by macrophages, resportion of edematous fluid by the lymphatic system
232
The activation of TLRs leads to upregulation of NF-κB, what effect does this nuclear transcription factor have on inflammation?
Activates immune response genes lead to the production of multiple immune mediators
233
An increase in body temperature is caused by what mediator
Prostaglandins
234
What process produces the stable fibrous scar?
Remodeling of the connective tissue
235
Extensive deposition of collagen in the lungs, liver, kidney and other organs as a result of chronic inflammation is termed?
Fibrosis
236
What TLR is located on macrophages and recognizes lipopolysaccharides on the membrane of gram-negative bacteria?
CD14
237
Through what mechanism do leukocytes move to the site of infection?
Extension of filipodia
238
What cytokines are involved in the systemic acute-phase response, including fever, and are also implicated in sepsis?
IL-1, TNF and IL-6
239
The MAC complex functions in cell lysis how?
MAC complex inserts into the cell membrane, making the cell more permable to water and ions
240
What lipid mediators are produced from arachidonic acid?
What other name refers to these mediators?
Prostaglandins and leukotrienes
Eicosanoids
241
When a granuloma is found, what disease should **always** be ruled out?
Mycobacterium Tuberculosis
242
Steps in scar formation
1. Angiogenesis
2. Formation of granulation tissue
3. Remodeling of CT
243
Histological appearance of granulation tissue
proliferation of fibroblasts
new blood vessels
Macrophages
244
TNF causes what pathologic effects in blood vessels?
Production of thrombus
245
What are the hallmarks of acute inflammation?
Presence of neutrophils and edema
246
What will cause lymphocytosis?
Viral infections, such as mono, that increase the number of lymphocytes in the blood count
247
What are some examples of non-caseating granulomas?
Sarcoidosis, cat scratch disease, chrons disease
248
What cell surface receptor is expressed on mast cells and what ligand binds?
FcεRI
bind the Fc region of IgE antibody
249
When an exudate is present, what does this imply?
There is an increase in permeability of the vessel endothelium (change in the tight junctions) as a result of tissue injury and an ongoing inflammatory rxn
250
Sensors that activate the inflammasome lead to the production of what cytokine?
IL-1
251
Once leukocytes migrate across endothelium, they move to the site of injury via the help of chemoattractants, both endogenous and exogenous, including:
_Exogenous_: bacteria with peptides that posses *N*-formylmethionine
_Endogenous_: cytokines (IL-8), complement (C5a), arachadonic metabolites (Leukotriene B4)
252
CNS macrophages
Microglia
253
Tissue repair by regeneration is dependent on?
The integrity of the ECM
254
C3a and C5a are considered to be anaphylatoxins because of their actions, what is it?
Stimulation of histamine release from mast cells, leading to vasodilation and increased vascular permeability
255
A substance that induces fever is referred to as?
A pyrogen
256
Where are toll like receptors (TLRs) located and what do they recognize?
Cells of the innate immune system ( macrophages and dendritic cells)
They recognize PAMPs located on pathogens
257
Serous inflammation is defined by
Exudation of cell poor fluid (transudate) into spaces created by cell injury or into body cavities lined with peritoneum (chest, abd, etc)
258
As blood flows slower, RBCs in small vessels concentrate and the viscosity of blood increases leading to
Stasis; the engorgement of small vessels with slow moving RBCs
259
What is a noraml total WBC count?
4,000 - 10,000
260
What cells are the source of histamine?
Mast cells
Basophils
Platelets
261
Spleen/lymph node macrophages
Sinus histiocytes
262
Purulent (suppurative) inflammation is characterized by the production of pus, commonly d/t infection by?
Bacteria that cause liquefactive necrosis, such as staphylococci
263
What is critical to the strength of a healing wound site?
Collagen synthesis
264
Firm adhesion, which occurs prior to transmigration, is mediated by what cell adhesion molecule?
Integrin
265
Factors that influence tissue repair
Infection
Diabetes
Nutritional status
Steroids
Mechanical factors
Poor perfusion
Foreign bodies
Type and extent of injury
Location of injury
266
What cytokines are released from M2 macrophages that have anti-inflammatory effects?
IL-10
TGF-β
267
Morphology of a granuloma
Epithelioid cells
Giant cells (fused activated macrophages)
Caseous necrosis (central area of necrosis)
268
What stimulates the liver to produce acute phase proteins?
IL-1 and IL-6
269
Clinical and pathologic changes associated with the acute-phase response include:
Fever
Acute-phase reactants
Leukocytosis
270
How do epithelioid cells present in granulomas form?
When activated macrophages develop abundant cytoplasm
271
What acute phase proteins are associated with the acute-phase response?
C-reactive protein (CRP)
Fibrinogen
Serum Amyloid A (SAA)
Hepcidin
272
Of the mediators, which is the **most important** for synthesis and deposition of connective tissue proteins
TGF-β
273
What cytokine is produced by TH1 cells and what is it's function?
INF-γ
Activation of M1 macrophages
274
Healing by CT replacement (scarring or fibrosis) typically occurs after substantial tissue destruction through what mechanism?
Organization
275
Fibrinous exudates occur commonly in what areas of the body?
lining of body cavities, such as the meninges, pericardium and pleura
276
Regeneration of the liver occurs through two mechanisms:
Proliferation of remaining hepatocytes
repopulation from progenitor cells
277
What is the triad of sepsis?
Disseminated intravascular coagulation
Hypotensive shock
Metabolic disturbances (insulin resistance, hyperglycemia)
278
What tissue types are unable to undergo repair d/t the fact that they cannot proliferate?
Brain
Heart
279
Stable cells, parenchyma of solid organs, are considered what kind of tissue?
Stable tissues
280
What cells are the source of prostaglandins and leukotrienes?
Mast cells
Leukocytes
281
Superoxide anion is converted into hydrogen peroxide (H2O2) through
spontaneous dismutation
282
What are acute-phase proteins?
Plasma proteins generated in the liver
283
What are the components of a Transudate?
low protein
little to no cellular material
low specific gravity
284
Deposition of CT is mediated by what factors?
PDGF, FGF-2, TGF-β
285
What types of granules do neutrophils have?
small specific granules
large azurophilic granules
286
Functions of the complement system
Inflammation
Opsonization
Cell lysis
287
Growth factors involved in tissue repair are released by what cell type?
Macrophages activated by tissue injury
288
Ulcerations occur when during healing?
When there is inadequate vascularization during healing
289
Contractures occur commonly after repair of injury induced by a burn, what is a contracture?
What are common places for contractures to occur?
Excessive contraction by myofibroblasts that leads to deformities in the wound and surrounding tissues
Commonly seen in the palms, soles, and anterior aspect of the thorax
290
Granuloma formation is induced by what cytokine?
INF-γ
