Lecture 8: Inflammation Flashcards

1
Q

what is the main goal of inflammation

A

restore homeostasis and allow healing

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2
Q

3 roles of inflammation

A
  • deliver effectors and cells from blood –> infection site
  • induce localized clotting
  • promote repair of damaged tissue
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3
Q

what happens once the acute inflammatory response is triggered

A
  • dilation and increased permeability of vasculature
  • influx of neutrophils (PMNs)
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4
Q

what cells exhibit an influx when chronic inflammation occurs

A

monocytes and lymphocytes

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5
Q

significant tissue damage can result in _____?

A

granulomas

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6
Q

what are the 3 components of the initial acute inflammation response

A
  1. vasodilation to increase blood flow to site of infection
  2. increased vascular permeability so immune cells can enter tissues
  3. increased expression of adhesion molecules, causes extravasation of neutrophils to site of infection
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7
Q

what types of receptors do macrophages and dendritic cells have to recognize PAMPs and DAMPs

A

Pattern Recognition Receptors

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8
Q

what does TLR4 bind to in order to trigger the activation of NkFB

A

TLR4 binds bacterial lipopolysaccharide (LPS) which triggers activation of NkFB and production of pro-inflammatory cytokines

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9
Q

what are the main pro-inflammatory cytokines

A

TNF-α, IL-1, IL-6, IL-12, and INF-γ

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10
Q

steps in extravasation

A
  • rolling adhesion
  • integrin activation
  • stable adhesion
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10
Q

what cell types produce pro-inflammatory cytokines

A
  • Macrophages
  • Dendritic cells
  • mast cells
  • endothelial
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11
Q

what do pro-inflammatory cytokines cause

A
  • induce expression of adhesion molecules allowing for the extravasation of WBCs
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12
Q

what are 2 important adhesion molecules induced by TNF-α and IL-1

A

selectins and ICAMS

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13
Q

what is the outcome of leukocyte adhesion deficiencies

A
  • no or poor adherence of immune cells to endothelial cells
  • poor extravasation
  • causes high WBC counts and recurrent infections
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14
Q

what are the 2 types of inflammatory mediators

A
  • plasma derived (liver)
  • cell derived
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15
Q

A plasma derived inflammatory mediator…

what is the result of the coagulation and Kinin system in response to damage

A
  • coagulation: production of blood clots
  • kinin: production of products w/ pro-inflammatory effects
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16
Q

A plasma derived inflammatory mediator

What is the effect of Anaphylatoxins C3a and C5a on inflammation

A
  • stimulate release of Histamine
  • stimulate immune cell chemotaxis and extravasation
  • vasodilation, fluid leakage
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17
Q
A
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18
Q

what are the cell-derived inflammatory mediators

A
  • histamine
  • arachidonic acid metabolits
  • cytokines
19
Q

what are the plasma-derived inflammatory mediators

A
  • Coagulation and Kinin systems
  • Anaphylatoxins C3a + C5a
20
Q

what is the effect of Histamine as a cell-derived inflammatory mediator

A

histamine binds H1 receptors causing
* vasodilation and endothelial cell contraction
* itch perception

21
Q

what is the effect of Arachidonic Acid Metabolites as cell-derived inflammatory mediators

A
  • production of thromboxanes, prostaglandins, leukotrienes which mediate inflammation
22
Q

what is the effect of cytokines as a cell-derived inflammatory mediator

A
  • regulate the immune system
  • Inflammasome = protein complex that triggers activation of caspases to cleave pro-IL 1β into active IL-1β
23
Q

what are acute phase proteins

A
  • C-reactive protein (CRP)
  • proteins whose concentration in blood plasma either increases or decreases in response to inflammation
  • produced in liver
24
Q

what cytokines stimulate acute phase proteins

A

TNF-α, IL-1, IL-6

25
Q

what is the function of C-reactive proteins

A
  • CRP concentration increases dramatically during inflammation
  • they bind lysophosphatidylcholine on dead/dying cells to induce classical complement via C1
26
Q

what is AA Amyloidosis

A
  • systemic condition that can develop in patients w/ chronic inflammatory diseases
  • elevated levels of pro-inflammatory cytokines lead to increased APP prouction
  • if left untreated, can cause excessive amyloid accumulation = kidney failure
26
Q

potential causes of prolonged inflammation (chronic)

A
  • persistent injury/infection
  • hypersensitivites and autoimmunity
  • prolonged exposure to toxins
27
Q

explain how chronic inflammation can result in tissue damage

A
  • monocytes become macrophages as they enter into tissues
  • continued stimulation of macrophages can lead to tissue damage
  • Granulomas can form to wall off persistent antigens
28
Q

what are 2 main inhibitory cytokines of the immune system

A

IL-10 and TGF-β

Produced by macrophages and T cells

29
Q

Granuloma formation is initiated by ______, secreted by _______ cells in order to enhacne macrophage activation

A

INFy, T-cells

30
Q

what inflammatory mediator do NSAIDs inhibit

A

prostaglandins

31
Q

what transcription factors are activated by the binding of a PAMP to a TLR

A

NFkB and IRF3

which then activate IL-1, IL-6, TNF-α

32
Q

what does tumor necrosis factor (TNFα) stimulate

A
  • T cell growth
  • actue phase response
  • triggers inflammation
33
Q

what interleukin promotes IFNα

A

IL - 18

34
Q

what does IL-6 stimulate

A
  • stimulates acute phase responses
  • promotes B cell differentiation
35
Q

what does IL-1 stimuate

A
  • stimulates acute phase response
  • costimulator of Th2 cells
36
Q

innate activation of macrophages occurs in response to…

A

TLR ligation

37
Q

what happens in the classical activation of macrophages

A
  • they become M1 cells by exposure to microbial products and Th1 cytokines (INFy)
38
Q

what happens in alternative activation of macrophages

A
  • they become M2 cells upon exposure to Th2
39
Q

functions of the reticuloendothelial system

A
  • destroy foregin substances
  • clean up dying / apoptoic cells
40
Q

cDC1 promotes type __?__ responses by producing IL __?__ and activating __?___ cells

A

type I responses by producing IL-12 and activating Th1 cells

41
Q

cDC2 promotes type __?__ responses by producing IL __?__ and activating __?___ cells

A

type II responses by producing IL-6 and IL-23 and activating Th2 and Th17 cells

42
Q

inflammasomes generate _____ that activates cytokines _____?_____

A

generate CASPACE1
activates cytokines ILB and IL18

43
Q

SAA and fibrinogen are examples of what

A

acute phase proteins

44
Q

antigen specificity of an antibody is determined by ?

A

combination of heavy and light chain domains

45
Q

what are the sickness cytokines?

A

IL-1, IL-6, HMGB1, TNF-α