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POM (Principles of Medicine) > Inflammation > Flashcards

Inflammation Flashcards

1
Q

What is inflammation?

A

A non-specific immune response to cellular injury designed to remove the cause & consequences of injury

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2
Q

What are the conical features of inflammation?

A 
Redness (Rubor)
Heat (Calor)
Swelling (Tumor)
Pain (Dolor)
Loss of function (Functio laesa)
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3
Q

What are the causes of inflammation?

A

Pathogens, allergens, autoantigens, physical damage, extreme temperatures, non-apoptotic cell death

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4
Q

What is acute inflammation?

A

Short term rapid response non-specific to cellular injury
Instantaneous changes to blood flow
recruitment of immune cells

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5
Q

What occurs to vasculature during acute inflammation?

A

Structural alterations to the microvasculature
Transient vasoconstriction of arterioles following vasodilation of arterioles and capillaries
Results in increased blood flow to the tissue, presenting rubor and callor

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6
Q

What cells are resident in the interstitium?

A

Resident macrophages, dendritic cells, mast cells

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7
Q

Where is the interstitium located?

A

The intermediate layer between the epithelium and the vascular endothelium

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8
Q

What generates inflammatory signals?

A

Non-apoptotic cell death (Damage-associated molecular patterns)
Pathogen-associated molecular patterns - lipopolysaccharides
Vasodilator release

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9
Q

Name the two main vasodilators:

A

Nitric oxide and histamine

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10
Q

How are vasodilators released from mast cells?

A

Mast cell degranulation

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11
Q

What is mast-cell degranulation?

A

The fusion of lysosomes and secretory vesicles to exocytose compounds

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12
Q

What effect does increased blood flow have in the local area of inflammation?

A

Locally raised temperature reduces the effectiveness of pathogen reproduction

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13
Q

What effect does histamine exert?

A

Increased permeability of vascular endothelium, resulting in an exudate forming within tissues,
Cells in walls withdraw from each other (diapedesis), leaky capillaries, the formation of tissue fluid

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14
Q

What is exudate?

A

Protein-rich fluid

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15
Q

What does exudation and increased blood flow result?

A

Stasis of circulation in area

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16
Q

Which cells release histamine?

A

Mast cells, basophils and platelets

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17
Q

What are the benefits of increased vascular permeability?

A

Increased antibody and leukocyte presence, increased availability of protein and formation of the barrier.

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18
Q

What is the cytokine network?

A

Interaction between macrophages and CD4 t cells

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19
Q

What inflammatory factor is released from macrophages?

A

Interleukin-1

GM-CSF

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20
Q

What is the function of IL-1?

A

Generates chemotactic signal of chemokines, activates T-cells

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21
Q

What is the role performed by IL-12?

A

Activates Th1, and NK cells

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22
Q

How is chemotaxis achieved?

A

Chemokines diffuse out to establish a chemical gradient, leukocytes expressing complimentary chemokine receptors migrate towards to chemokine source

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23
Q

What is CXCL8?

A

IL-8

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24
Q

Which cell secrete CXCL8?

A

Macrophages

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25
Q

What is the role of CXCL8?

A

Chemotactic attract for neutrophils , neutrophil migration to the site of infection

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26
Q

What receptors do CXCL8 bind to?

A

G-coupled 7-TM proteins (CXCR-1/2)

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27
Q

Which cells are the initial responders to inflammation?

A

Neutrophils

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28
Q

How do cytokines influence adhesion molecules?

A

Upregulates endothelial production of adhesion molecules

29
Q

Which cell secretes chemoattract cytokines?

A

Macrophages

30
Q

What is the main example of an adhesion molecule?

A

E and P-Selectins

31
Q

What is the first step of neutrophil migration?

A

Rolling and adhesion

32
Q

Describe the neutrophil binding with the endothelial cell surface:

A

Establishes reversible binding between selectins induced on the endothelial cell surface and carbohydrate ligands in a low-affinity state

33
Q

Which ligand binds onto P and E-selectins?

A

PSGL-1 (Selectin-P ligand)

34
Q

Which switch ensures that there is a tight adhesion to the endothelial surface?

A

Low to high-affinity switch in integrins

35
Q

What are the two integrin ligands?

A

LFA-1, MAC-1 (high affinity)

36
Q

Which factors promote the low-high affinity switch in neutrophil tight adhesion? (Selectin –> integrin-mediated)

A

IL-8
C5A
Leukotriens LTB4
Formylated peptides and platelet activating factor

37
Q

Which molecule presented on the endothelial surface interacts with the neutrophil integrins, MAC-1, LFA-1?

A

ICAM-1/2

38
Q

Which chemotaxin gradient do neutrophils migrate across?

A

IL-8

39
Q

Which molecule secreted by endothelial cells stimulates diapedesis?

A

CD99

40
Q

How do infiltrating neutrophils pass through the endothelial membrane?

A

Disrupts the interactions of junction adhesion molecules (JAM) and vascular endothelial cadherins (VE-cadherin)

41
Q

How is the rearrangement of the cytoskeleton of pseudopodia caused during the neutrophil invasion?

A

PECAM interactions

42
Q

Which cells release prostaglandins?

A

Mast cells, leukocytes

43
Q

What action do prostaglandins exhibit?

A

Vasodilation, pain, fever

44
Q

Which cells secrete TNF, and IL-1?

A

Macrophages, endothelial cells, mast cells

45
Q

What is the role performed by TNF & IL-1?

A 
Endothelial activation (adhesion molecules)
fever, malaise, pain, and anorexia, shock
46
Q

Which cells secrete chemokines?

A

Macrophages and leukocytes

47
Q

What is the role performed by chemokines?

A

Chemotaxis

Leukocyte activation

48
Q

Which receptors identify pathogen-associated molecular patterns (PAMPs)?

A

Toll-like receptors

CD14

49
Q

Give an example of a PAMP?

A

Lipopolysaccharides present on gram-negative bacteria

50
Q

Which enzymes are secreted by lysosomes?

A

Lysozyme and elastase

51
Q

What is the role of reactive oxygen species & NADPH oxidase?

A

Secreted to interfere and disrupt microbial function

52
Q

What is netosis?

Hint: NETs

A

Neutrophil extracellular traps (NETs) are networks of extracellular fibres composed of neutrophil DNA which bind pathogens

53
Q

How long is the half-life of activated neutrophils?

A

Short half-life

54
Q

What is the resolution of an acute inflammatory response??

A

Clearance of apoptotic cells and produce anti inflammatory mediators
Repair: ECM & granularof formation

55
Q

What are the sensory stimulatory signals transmitted by nociceptor neurons?

A

PGEs and histamines

56
Q

What is chronic inflammation?

A

Arises as a response to injury with associated

Fibrosis occurring over a prolonged period of time in comparison with acute inflammation

57
Q

The formation of which structure characterizes chronic inflammation?

A

Granulomas

58
Q

Why does chronic inflammation occur?

A

Persistent exposure to stimuli

59
Q

What are the examples of persistent stimuli?

A

Infection (TB, Hepatitis)
Pollutants and allergens
Inclearable particulates
Auto-immunity

60
Q

Which cells are involved in chronic inflammation?

A

Inflammatory macrophages
T cells
Plasma cells

61
Q

What are the roles performed by macrophages?

A

Phagocytosis of pathogens & necrotic cells
Recognize and engulf apoptotic cells
Anti-inflammatory responses through cytokine release
Antigen-presenting cells
Promotes tissue repair through stimulating angiogenesis and fibrosis

62
Q

Whare are regulatory T cells? (Treg)

A

Regulate the effector and activation stages of T-cells, secretes IL-10
Downregulates macrophages

63
Q

What is granulomatous inflammation?

A

Chronic inflammation with a distinct pattern of granuloma formation

64
Q

What are granulomas?

A

Aggregation of activated macrophages forms when the immune system attempts to form a clearance barrier, surrounding the pathogen
Prevents infection spread.

65
Q

Compare the onset of acute and chronic inflammation:

A 
Immediate onset (lasts few days)
v
Delayed onset (Last weeks, months, years)
66
Q

Compare the immune cells present in both types of inflammation:

A

Neutrophils
V
Macrophages & Monocytes

67
Q

What are the chemical releases in acute and chronic inflammation?

A

Histamine
v
Cytokine release

68
Q

What are the outcomes of acute inflammation?

A

Complete resolution

Progression to chronic

69
Q

What are the outcomes of chronic inflammation?

A

Scarring

Loss of function

POM (Principles of Medicine) (34 decks)

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