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Molecular Immunology > Lecture 10: Inflammation > Flashcards

Lecture 10: Inflammation Flashcards

1
Q

Hallmark of acute inflammation vs. chronic?

A

Acute: PMN (neutrophil) influx - first line of defense

Chronic: accumulation and activation of macrophages/lymphocytes; granuloma

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2
Q

True or False: Increased blood flow and lymphatic flow are feature of acute inflammation

A

True

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3
Q

In acute inflammation, released components destroy infectious agents, clear cell debris and induce release of cytokines that promote ___ deposition and healing

A

fibrin

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4
Q

What does acute inflammation occur in response to?

A

1) Host produced factors
2) Components of microorganisms
3) Host tissue breakdown by products

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5
Q

What are the five cardinal signs of inflammation?

A

1) LOF (reflex muscle inhibition, pain)
2) Pain (nociceptor stimulation)
3) Swelling (vascular permeability)
4) Erythema (vasodilation)
5) Heat (vasodilation)

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6
Q

Capillary widening increases blood flow, promoting ___

A

heat

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7
Q

Four main cytokines that contribute to inflammation?

A

IL-1, IL-6, IL-8, and TNF-alpha

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8
Q

Which cytokine is a chemotacic (chemoattraction of neutrophils) that activates phagocytes?

A

IL-8
- Local impact

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9
Q

True or False: IL-1, IL-6, and TNF-alpha induces fever as systemic response

A

True

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10
Q

Which cytokine is important for locally:
- activating macrophages+lymphocytes
- causing tissue destruction
- affecting endothelium

A

IL-1

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11
Q

True or False: TNF-alpha can have systemic effects (namely: fever and induction of IL-6)

A

False: IL-1 can have systemic effects (namely: fever and induction of IL-6)

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12
Q

Local effect of IL-6?

A

Activates lymphocytes

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13
Q

What are the two systemic effects of IL-6

A

1) fever
2) induction of acute phase proteins

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14
Q

What are the two systemic effects of TNF-alpha?

A

1) fever
2) shock

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15
Q

True or False: At a local level, both IL-1 and TNF-alpha activate macrophages and effect the endothelium

A

True

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16
Q

what is the only cytokine that increase vascular permeability at a local level?

A

TNF-alpha

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17
Q

Local inflammation is accompanied by a systemic response known as the ____

A

acute phase response

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18
Q

Characteristics of acute phase response?

A

many acute phase proteins (via liver)

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19
Q

True or False: Acute phase proteins are potent substances that can induce localized and systemic response

A

True

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20
Q

Acute phase proteins are mainly produced in response to ___, ____, and ___

A

IL-1, IL-6, and TNF-alpha

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21
Q

Fibrinogen is only regulated by which cytokine?

A

IL-6

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22
Q

True or False: CRP is made in liver in response to IL-1, IL-6, or TNF-alpha

A

True

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23
Q

What type of enzymes cleave CRP into peptides that opsonize, enhance complement fixation, and induce chemotaxis?

A

Neutrophil enzymes

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24
Q

What is the most widely used indicator of acute phase response?

A

CRP

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25
___ is an acute phase protein that reduces charge on RBC, allowing for better clumping and better sediment
Fibrinogen
26
True or False: An ESR is a convenient way of measuring inflammation
True - If inflammation is occur, you would expect to see elevated ESR (meaning: elevated fibrinogen and clumping)
27
What molecule is good for monitoring Tb, rheumatoid fever, and MI?
ESR
28
True or False: Changes to endothelium makes it possible for immune cells to leave the blood extravasate to site of injury
True
29
____: movement of WBC's through unruptured vessels wall into surrounding tissue
Extravasation
30
Four steps of extravasation?
1) Rolling 2) Tight Binding 3) Diapedesis 4) Migration/Chemotaxis
31
The first step of extravastion (rolling) is also know as: ___ or ____
tethering ; pavementing
32
Within minutes of exposure to an acute inflammatory signals, ____ molecules on vascular endothelium are expressed
cell adhesion molecules
33
True or False: In Phase 1 (Rolling) of extravasation, WBC's on cell surface increase, leading to more sticky-ness
True
34
Main player (located on endothelial cell) during rolling phase of extravasation?
E-selectin
35
E-selectin binds to ____, a carbohydrate found on neutrophils
Siayl-Lewis
36
Rolling allows for signaling between ___ and ___, which activates ___ on neutrophils.
endothelial cell; neutrophil integrins
37
The second stage of extravasation is mediated by _____, which is located on the endothelial cell
Endothelial ICAM-1
38
What two neutrophil integrins bind to endothelial ICAM-1 during second stage of extravasation?
CD11a/CD18 (LFA-1) CD11b/CD18 (MAC-1)
39
Which has tighter binding: stage 1 or stage 2 of extravasation?
Stage 2
40
Transendothelial migration is a feature of which stage of extravasation?
Stage 3 (Diapedesis)
41
In Stage 3 - Diapedesis, endothelial CD31 (aka PECAM) binds to which neutrophil structure?
CD31 (PECAM) binds to neutrophil integrins
42
How is chemotaxis regulated?
1) Receptors on neutrophils 2) Chemotactic factors - Chemokine (IL-8) - Cytokine (TNF-a) - Complement (C5a, C3a)
43
___: directional movement of cells using concentration gradient of a substance
Chemotaxis
44
___ are the first leukocytes from the circulation that enter site of inflammation and infection?
Neutrophils
45
What three enzymatic cascades are initiated when fluid enters tissues during inflammation?
1) Complement (C5a - anaphylatoxin, C3b - opsonins) 2) Coagulation (Factor XII) 3) Fibrinolytic
46
____ is a product of the Fibrinolytic Pathway. It acts as a chemoattractant and activates alternative c' pathway.
Fibrinopeptide
47
True or False: Coagulation system limits microbe movement beyond initial site of infection
True
48
What is the role of complement, coagulation, and fibrinolytic pathway during acute inflammation?
Work together to recruit cells from bloodstream and help activation once they get there
49
At site of inflammation, phagocytes get signals that enhance phagocytic ability, leads to production of?
1) N radicals 2) ROS 3) O2- 4) H2O2 5) NO 6) Proteolytic enzymes - collagenase, elastase
50
How do ROS, O2-, H2O2, etc. made by phagocytes affect membrane lipids + capillary permeability?
Damages membrane lipids Increases capillary permeability
51
What is the value of production of proteolytic enzymes by macrophages?
Enhances movement of inflammatory cells through tissues
52
During acute inflammation, what cells are recruited from blood?
1st - neutrophils (PMN's) Others (chemotaxis) - C5a - fibrinopeptide B - IL-8
53
True or False: If left unchecked, acute inflammation can cause severe tissue damage
True
54
In chronic inflammation, which cell arrives first? after?
first = neutrophils/PMN's after = monocytes/lymphocytes (mononuclear cells)
55
Predominant inflammatory cell in acute inflammation? chronic inflammation?
acute = neutrophils chronic = lymphocytes and macrophages
56
In chronic inflammation, ____ tries to clean up initial mess made by neutrophils
macrophages
57
Five cells of chronic inflammation?
1) plasma 2) giant 3) eosinophils 4) fibroblasts 5) lymphocytes
58
Functions of macrophages in chronic inflammation?
1) Phagocytose 2) Secrete enzymes 3) Release TGF-B - attract fibroblasts and stimulate them to make COLLAGEN
59
What type of inflammation is characterized by prolonged chemotactic stimulation, resulting in perpetual arrival of new macrophages, T cells, plasma cells, fibroblasts?
Chronic inflammation
60
Which cell type contributes to neovascularization in chronic inflammation?
Macrophages
61
What cells are found in a granuloma?
1) Activated macrophages 2) Epitheloid cells 3) Th cells 4) Giant cells
62
In the early stages of granuloma formation, macrophages with lots of cytoplasm, known as ____, form
epitheloid cells
63
Epitheloid cells are surrounded by ___ cells
T cells
64
In granuloma formation, what cytokines are made by T helper cells? What cytokines are made by macrophages?
T helper: IFN-gamma; IL-4 Macrophages: TNF-alpha; IL-1
65
Macrophages make TNF-alpha and TGF-beta. How do they aid granuloma formation?
TNF-alpha = activates macrophages; works with IFN-gamma TNF-beta = fibrosis and scarring
66
CD4+ T cells aid granuloma formation by secreting IL-4, IL-1, and IFN-gamma. What are these cytokines role?
IL-4: aggregation and macrophage fusion IL-1: protease production IFN-gamma: activates macrophages; inhibits migration
67
Phases of infection?
1) Pathogen breaks barrier 2a) Acute inflammation - Recruits neutrophils (first) - via extravasation 2b) Monocytes try to help - lead to chronic inflammation and granuloma
68
True or False: A cardinal sign of acute inflammation is erythema and the main process that underlies it is macrophage-released IL-6
False - the underlying cause of erythema (redness) is increased blood flow and vascular permeability which result in red blood cell accumulation
69
True or False: IL-8 is a macrophage-produced cytokine that induces fever
False - IL-1, TNF-a, and IL-6 induce fever, but IL-8 is not known to induce a fever
70
The “tight binding” step in the process of extravasation of neutrophils to sites of inflammation within a tissue is mediated by: A. EC E-selectin binding neutrophil sialyl-Lewisx B. EC integrins binding neutrophil ICAM-1 C. EC CD31 binding neutrophil integrins D. EC IL-8 binding neutrophil IL-8 receptor E. EC ICAM-1 binding neutrophil integrins
E. EC ICAM-1 binding neutrophil integrins

Molecular Immunology (27 decks)

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