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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
Q

___ is an acute phase protein that reduces charge on RBC, allowing for better clumping and better sediment

A

Fibrinogen

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26
Q

True or False: An ESR is a convenient way of measuring inflammation

A

True
- If inflammation is occur, you would expect to see elevated ESR (meaning: elevated fibrinogen and clumping)

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27
Q

What molecule is good for monitoring Tb, rheumatoid fever, and MI?

A

ESR

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28
Q

True or False: Changes to endothelium makes it possible for immune cells to leave the blood extravasate to site of injury

A

True

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29
Q

____: movement of WBC’s through unruptured vessels wall into surrounding tissue

A

Extravasation

30
Q

Four steps of extravasation?

A

1) Rolling
2) Tight Binding
3) Diapedesis
4) Migration/Chemotaxis

31
Q

The first step of extravastion (rolling) is also know as: ___ or ____

A

tethering ; pavementing

32
Q

Within minutes of exposure to an acute inflammatory signals, ____ molecules on vascular endothelium are expressed

A

cell adhesion molecules

33
Q

True or False: In Phase 1 (Rolling) of extravasation, WBC’s on cell surface increase, leading to more sticky-ness

34
Q

Main player (located on endothelial cell) during rolling phase of extravasation?

A

E-selectin

35
Q

E-selectin binds to ____, a carbohydrate found on neutrophils

A

Siayl-Lewis

36
Q

Rolling allows for signaling between ___ and ___, which activates ___ on neutrophils.

A

endothelial cell; neutrophil
integrins

37
Q

The second stage of extravasation is mediated by _____, which is located on the endothelial cell

A

Endothelial ICAM-1

38
Q

What two neutrophil integrins bind to endothelial ICAM-1 during second stage of extravasation?

A

CD11a/CD18 (LFA-1)
CD11b/CD18 (MAC-1)

39
Q

Which has tighter binding: stage 1 or stage 2 of extravasation?

40
Q

Transendothelial migration is a feature of which stage of extravasation?

A

Stage 3 (Diapedesis)

41
Q

In Stage 3 - Diapedesis, endothelial CD31 (aka PECAM) binds to which neutrophil structure?

A

CD31 (PECAM) binds to neutrophil integrins

42
Q

How is chemotaxis regulated?

A

1) Receptors on neutrophils
2) Chemotactic factors
- Chemokine (IL-8)
- Cytokine (TNF-a)
- Complement (C5a, C3a)

43
Q

___: directional movement of cells using concentration gradient of a substance

A

Chemotaxis

44
Q

___ are the first leukocytes from the circulation that enter site of inflammation and infection?

A

Neutrophils

45
Q

What three enzymatic cascades are initiated when fluid enters tissues during inflammation?

A

1) Complement (C5a - anaphylatoxin, C3b - opsonins)
2) Coagulation (Factor XII)
3) Fibrinolytic

46
Q

____ is a product of the Fibrinolytic Pathway. It acts as a chemoattractant and activates alternative c’ pathway.

A

Fibrinopeptide

47
Q

True or False: Coagulation system limits microbe movement beyond initial site of infection

48
Q

What is the role of complement, coagulation, and fibrinolytic pathway during acute inflammation?

A

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

49
Q

At site of inflammation, phagocytes get signals that enhance phagocytic ability, leads to production of?

A

1) N radicals
2) ROS
3) O2-
4) H2O2
5) NO
6) Proteolytic enzymes - collagenase, elastase

50
Q

How do ROS, O2-, H2O2, etc. made by phagocytes affect membrane lipids + capillary permeability?

A

Damages membrane lipids
Increases capillary permeability

51
Q

What is the value of production of proteolytic enzymes by macrophages?

A

Enhances movement of inflammatory cells through tissues

52
Q

During acute inflammation, what cells are recruited from blood?

A

1st - neutrophils (PMN’s)

Others (chemotaxis)
- C5a
- fibrinopeptide B
- IL-8

53
Q

True or False: If left unchecked, acute inflammation can cause severe tissue damage

54
Q

In chronic inflammation, which cell arrives first? after?

A

first = neutrophils/PMN’s
after = monocytes/lymphocytes (mononuclear cells)

55
Q

Predominant inflammatory cell in acute inflammation? chronic inflammation?

A

acute = neutrophils
chronic = lymphocytes and macrophages

56
Q

In chronic inflammation, ____ tries to clean up initial mess made by neutrophils

A

macrophages

57
Q

Five cells of chronic inflammation?

A

1) plasma
2) giant
3) eosinophils
4) fibroblasts
5) lymphocytes

58
Q

Functions of macrophages in chronic inflammation?

A

1) Phagocytose
2) Secrete enzymes
3) Release TGF-B - attract fibroblasts and stimulate them to make COLLAGEN

59
Q

What type of inflammation is characterized by prolonged chemotactic stimulation, resulting in perpetual arrival of new macrophages, T cells, plasma cells, fibroblasts?

A

Chronic inflammation

60
Q

Which cell type contributes to neovascularization in chronic inflammation?

A

Macrophages

61
Q

What cells are found in a granuloma?

A

1) Activated macrophages
2) Epitheloid cells
3) Th cells
4) Giant cells

62
Q

In the early stages of granuloma formation, macrophages with lots of cytoplasm, known as ____, form

A

epitheloid cells

63
Q

Epitheloid cells are surrounded by ___ cells

64
Q

In granuloma formation, what cytokines are made by T helper cells?

What cytokines are made by macrophages?

A

T helper: IFN-gamma; IL-4

Macrophages: TNF-alpha; IL-1

65
Q

Macrophages make TNF-alpha and TGF-beta. How do they aid granuloma formation?

A

TNF-alpha = activates macrophages; works with IFN-gamma
TNF-beta = fibrosis and scarring

66
Q

CD4+ T cells aid granuloma formation by secreting IL-4, IL-1, and IFN-gamma. What are these cytokines role?

A

IL-4: aggregation and macrophage fusion
IL-1: protease production
IFN-gamma: activates macrophages; inhibits migration

67
Q

Phases of infection?

A

1) Pathogen breaks barrier
2a) Acute inflammation
- Recruits neutrophils (first) - via extravasation

2b) Monocytes try to help - lead to chronic inflammation and granuloma

68
Q

True or False: A cardinal sign of acute inflammation is erythema and the main process that underlies it is macrophage-released IL-6

A

False - the underlying cause of erythema (redness) is increased blood flow and vascular permeability which result in red blood cell accumulation

69
Q

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

A

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

70
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. EC ICAM-1 binding neutrophil integrins

Molecular Immunology (27 decks)

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