Test 3- L10 Flashcards

1
Q

What is the definition of acute inflammation

A

The rapid response (within minutes to hours) of tissues to injury and/or infection

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2
Q

What is the net result of inflammation

A

Release of vascular components into extravascular locations, increased blood and lymphatic flow

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3
Q

What do the released components of inflammation do

A

Destroy infectious agents, clear cell debris, and induce the release of cytokines that promote fibrin deposition and healing

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4
Q

What is the hallmark of inflammation

A

Influx of polymorphonuclear cells (neutrophils)

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5
Q

What does acute inflammation occur in response to

A

Host-produced factors, components of microorganisms (PRRs),
host tissue breakdown by-products

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6
Q

5 common signs of inflammation

A

Heat, redness, swelling, pain, loss of function

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7
Q

What causes the heat and redness from infection

A

Vasodilation (increased blood flow)

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8
Q

What causes the swelling associated with inflammation

A

Increased vascular permeability—> fluid release into tissues

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9
Q

What causes the pain associated with inflammation

A

Stimulation of nocireceptors

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10
Q

What causes the loss of function associated with inflammation

A

Pain, reflex muscle inhibition, disruption of tissue structure, fibroplasia/ metaplasia

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11
Q

What is the systemic response to inflammation

A

Fever & proliferation of leukocytes

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12
Q

What are the 4 main cytokines that contribute to inflammation

A

IL-1,IL-6,IL-8,TNF-α

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13
Q

When the cytokines are released in a controlled manner what do they lead to

A

Inflammation

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14
Q

If the stimulus that induces the release of the main cytokines isn’t easily removed what happens

A

Systemic release of these proteins lead to systemic changes

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15
Q

Example of when the cytokines would be released

A

Macrophage ingests gram negative bacteria containing LPS and is activated to secrete cytokines

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16
Q

What local and systemic effect does IL-8 have

A

Local: Chemotactic (chemoattractant), activates phagocytes
Systemic effects: none

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17
Q

What are the local and systemic effects of IL-1?

A

Local: Activates lymphocytes & macrophages, effects endothelium, local tissue destruction
Systemic effect: Fever, induction of IL-6

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18
Q

What local and systemic effect does TNFα have

A

Local: Effects endothelium, vascular permeability, activates macrophages
Systemic effect: Fever, shock

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19
Q

What local and systemic effects does IL-6 have

A

Local: Activates lymphocytes
Systemic effect: Fever, induction of acute phase proteins

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20
Q

Local inflammation is accompanied by a systemic response called

A

Acute-phase response

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21
Q

What is the acute phase response characterized by

A

Production of lots of acute phase proteins by the LIVER

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22
Q

The acute phase proteins are produced in response to

A

Macrophage produced cytokines- IL-1, IL-6, TNFα

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23
Q

What induces acute phase protein- C-reactive protein

A

IL-6, IL-1, TNFα

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24
Q

What induces acute phase protein- Fibrinogen

A

ONLY IL-6

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25
Q

C-reactive protein (CRP) is the most widely used indicator of what

A

An acute-phase response in humans for early detection of infections, inflammation, or other disease assoc. with tissue injury

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26
Q

CRP is synthesized where in response to what

A

Liver, IL-1, TNF, IL-6

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27
Q

Neutrophil enzymes cleave CRP into peptides that do what

A

Oposnize, enhance complement fixation, induce chemotaxis

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28
Q

Fibrinogen is an acute phase protein that does what

A

Reduces charge on RBCs (allows for better aggregation of RBCs), enhances their ability to sediment

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29
Q

Erythrocyte sedimentation rate (ESR) is a measure of what

A

The level of inflammation that is going on in a patient

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30
Q

If inflammation is occurring what is increased

A

Increased fibrinogen—> increased clumping—> increased ESR

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31
Q

What is an ESR useful for monitoring

A

TB, tissue necrosis, rheumatic fever, heart attack, malignant diseases

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32
Q

Chemical mediators mentioned impact what

A

Endothelial cells of local blood vessels, make it easier for immune cells to leave endothelium and extravasate to the site of injury/ infection

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33
Q

What is extravasation

A

The movement of white blood cells through an unruptured vessel wall into the surrounding tissue

34
Q

What are the 4 steps of extravasation

A

Rolling, tight binding, diapedesis, chemotaxis

35
Q

Step 1 (Rolling)- within minutes of exposure to an acute inflammatory signal (TNFα, leukotrienes, C5a, vasoactive peptides) induce what

A

Cell adhesion molecules on endothelium adjacent to the site of infection/injury

36
Q

What is the main player on endothelial cells that increase its ‘stickiness’

A

E-selectin

37
Q

What is the main player on neutrophils that increase its ‘stickiness’

A

Sialyl- Lewis (a carbohydrate on neutrophils)

38
Q

What does rolling (step 1) allow

A

Signaling between the endothelial cell and the neutrophil to activate integrins on the neutrophil, which mediate Step 2, which is tight
binding of the neutrophil to the vessel

39
Q

Step 2- Tight binding is mediated by

A

Endothelial ICAM-1

40
Q

What does ICAM-1 bind to

A

Neutrophil integrins –
CD11a/CD18 (aka LFA-1:
leukocyte functional antigen-1), CD11b/CD18 (aka Mac-1)

41
Q

Step 3 Diapedesis is what

A

The passage of white blood cells through the intact wall of a blood vessel (transendothelial migration)

42
Q

Diapedesis is mediated by what molecules binding

A

Endothelial CD31, Neutrophil integrins

43
Q

What is step 4

A

Chemotaxis

44
Q

What is chemotaxis

A

Directional movement of cells using a concentration gradient of a substance

45
Q

What is chemotaxis regulated by

A

Receptors present on the neutrophil and a substance
originating from the
inflammatory stimulus

46
Q

The substance
originating from the
inflammatory stimulus that induces chemotaxis is what

A

Chemokine such as IL-8, cytokine such as TNF α, complement components (C5a, C3a), fibrinolytic peptides, histamine, microbial products
(LPS, fMLP)

47
Q

What are the first leukocytes from the circulation entering the site of inflammation or infection

A

Neutrophils (a type of PMN)

48
Q

Neutrophils are the hallmark of what

A

Acute inflammatory response

49
Q

What is the first line of defense against inflammation

A

Neutrophils

50
Q

What are the 3 enzymatic cascades initiated when
fluid enters tissues during inflammation that contribute to inflammatory process during acute inflammation

A

The complement system, the coagulation system, the fibrinolytic system

51
Q

What does the complement system do

A

Create opsonins (C3b) and anaphylatoxins (C5a) that act as chemokines to recruit cells to the site

52
Q

What does the coagulation system do

A

Forms barrier to limit microbe movement beyond initial site of infection

53
Q

What does the fibrinolytic system do

A

Fibrinopeptide is created and acts as a chemoattractant and activates alternative pathway

54
Q

The 3 enzymatic cascades do what

A

Work together to recruit cells from the bloodstream and help their activation once they get there

55
Q

At the site of inflammation, phagocytes receive signals
that enhance their phagocytic ability, producing:

A

Superoxide, hydrogen peroxide, nitric oxide, other reactive oxygen and nitrogen radicals

56
Q

Phagocytes release what

A

Proteolytic enzymes

57
Q

What is the damage that the products of phagocytes produces

A

Damage cellular metabolism and membrane lipids, leading to more factors that increase capillary permeability

58
Q

Phagocytes release what proteolytic enzymes and what do they do

A

Collagenases, elastases, other proteases (can convert cytokines to active or inactive forms), enhance movement of inflammatory cells through tissues

59
Q

4 steps of acute inflammation

A

1: Cells are recruited from blood (chemotaxis due to C5a, fibrinopeptide B, IL-8), neutrophils are recruited first
2: Once there phagocytes release proteolytic enzymes to enhance movement of
inflammatory cells at the site of infection (collagenases, elastases)
3: Phagocytes also produce and “listen to” signals that increase their activity (superoxide, hydrogen peroxide, NO)
4: Cells try and remove the stimulus

60
Q

Hours after neutrophils arrive at the site of infection/injury, what cells arrive

A

Monocytes and lymphocytes (mononuclear cells)

61
Q

What attracts the mononuclear cells

A

The same factors that attracted neutrophils, but in higher concentrations

62
Q

Why are macrophages brought in

A

To clean up the mess created by neutrophils

63
Q

What is the hallmark of chronic inflammation

A

Accumulation and activation of macrophages/ lymphocytes

64
Q

What are the cells of chronic inflammation

A

Lymphocytes, eosinophils, plasma cells, giant cells, fibroblasts

65
Q

What are chronic inflammatory lesions composed of

A

Can be purely Macrophages, lymphocytes, or plasma cells

66
Q

What are 3 things activated macrophages do in chronic inflammation

A

1-Phagocytose bacteria, dead neutrophils, damaged tissue or cells, fibrin deposits, etc.
2-Secrete collagenases, elastases, gelatinases that directly destroy
connective tissue
3- Release transforming growth factor-β(TGF-β) which attracts fibroblasts and stimulates them to secrete collagen to repair
damaged tissue

67
Q

If macrophages and neutrophils are incapable of removing the cause- what may form

A

A granuloma

68
Q

What does prolonged chemotactic stimulation result in for chronic inflammation

A

Perpetual arrival of
new macrophages, T cells, plasma cells, and fibroblasts
* Fibroblasts contribute to excessive collagen deposition around the irritant
* Macrophages contribute to excessive neovascularization which aids the inflammatory response to continue

69
Q

What is a granuloma

A

Tumor-like mass or nodule that arises because of a chronic inflammatory response

70
Q

What is a granuloma composed of

A

Many activated macrophages, epithelioid cells, T helper cells, multinucleated giant cells formed by the fusion of macrophages

71
Q

Formation of a granuloma in an attempt to do what

A

“Wall-off” the organism, and release high concentrations of lytic enzymes which destroy surrounding tissue leading to damage of blood vessels with extensive tissue necrosis

72
Q

The formation of granulomas can happen in response to what bacteria

A

Mycobacterium Tuberculosis

73
Q

Macrophages with lots
of cytoplasm form called
what

A

Epithelioid cells

74
Q

Multiple epithelioid cells joined together form a

A

Multinucleated giant cell

75
Q

What are the cytokines important in granuloma formation that come from CD4+ cells

A

-IL-4 - causes aggregation and fusion of macrophages
-IFN-γ - potent activator of macrophages and monocytes, causes cell
fusion, inhibits migration (negative chemotactic signal)
-IL-1- stimulates production of proteases which break down the
extracellular matrix

76
Q

What are the cytokines important in granuloma formation that come from macrophage cells

A

-TNF-α - potent macrophage activator and works synergistically
with IFN-γ
-TGF-β- stimulates fibrosis and scarring

77
Q

3 hallmarks of granulomas

A

1- development of a necrotic center
2-Fibrosis & scar formation (healing)
3-Enlargement & replacement of normal tissue

78
Q

If neutrophils dont stop the infection/ injury what is recruited

A

Monocytes

79
Q

The proper order of steps in neutrophil extravasation (from left to right) is:
A. diapedesis → rolling →tight binding → chemotaxis
B. rolling → diapedesis → tight binding → chemotaxis
C. chemotaxis → tight binding → diapedesis → rolling
D. rolling → tight binding → diapedesis →chemotaxis
E. None of the above

A

D

80
Q

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

A

E

81
Q

True or False?
IL-8 is a macrophage-produced cytokine that induces fever

A

FALSE: IL-1, TNF-α, and IL-6 induce fever, but IL-8 is not known to induce a fever