Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

BoD > Inflammation > Flashcards

Inflammation Flashcards

1
Q

How do many cells recognise the presence of danger

A

By expressing Pattern Recognition Receptors (PRRs) which recognise PAMPs and DAMPs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Give 5 facts about PAMPs

A

Shared by classes of organisms

Essential for survival of the pathogen

Highly conserved

Absent from the vertebrate host

Allow the innate system to distinguish between self and non-self

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are PAMPs usually apart of in the bacteria’s anatomy

A

Essential components of the bacterial cell wall or cell membrane (eg peptidoglycan)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Name a PAMP for gram positive and gram negative bacteria

A

Gram positive: lipoteichoic acid

Gram negative: LPS (lipopolysacchride)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Are PAMPs shared between gram positive and negative bacteria?

A

Some are (lipoproteins) but some are specific to gram positive (lipoteichoic acid) or gram negative (LPS)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What differentiates bacteria genome from the host DNA

A

Unmethylated CpG - mammals have a lower frequency of CpG dinucleotide which are misty methylated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Define PRR

A

Germline encoded molecules that monitor the internal and/or external environment of the cell for PAMPs and DAMPs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

true or false

All pattern recognition receptors are found at the plasma membrane

A

False

They can be located at the plasma membrane, in endosomes, or in the cytosol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Name a soluble PRR

A

CRP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Give three functions of pattern recognition receptors

A

Stimulate ingestion of microbes by phagocytosis

Act as chemotactic receptors and guide cells to sites of infection

Produce effector molecules that assist both the innate and adaptive response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What was the first family of PRRs to be identified

Describe them

A

TLRs (Toll Like Receptors)

Transmembrane proteins that act as sensors of microbes in extracellular spaces

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

When are TLRs functional

A

As dimers (either homo- or heterodimers)

Each dimer pair is specific for a different set of pathogen products

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How many functional TLR genes do humans have

A

10

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What happens upon recognition of a TLR’s specific ligand

A

TLR induces signalling cascades that lead to activation of innate immune responses that combat infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Which TLRs are located on the cell-service

A

TLRs 1,2,4,5,6,10

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Which TLRs are located in endosomes?

What do these recognise

A

TLRs 3,7,8,9

Microbial Nucleic acid including dsRNA, ssRNA and DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What do TLRs do when activated

A

Recruit signalling adaptor molecules - importantly MyD88 and TRIF - and initiate downstream signalling events (activation of NF-κB, AP-1, and IRF 3 and 7) leading to release of products (eg inflammatory cytokines, Type 1 interferons, chemokines)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the most important signalling adaptor molecules recruited by TLRs

A

MyD88

TRIF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Give an example of a host DAMP recognised by TLRs

A

High Mobility Group Box-1 (HMGB-1)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

In general what do the following stimulate in TLRs:

a) bacterial products
b) viral products

A

a) pro-inflammatory response (NF-κB and AP-1)

b) anti-viral interferon response (IRFs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Name three other major families of PRR (not TLRs)

What are each important in

A

C-type lectin receptors (CLR) - fungal infections

RIG-I-like receptors (RLR) - detection of viral RNA in the cytoplasm

Cytosolic NOD-like receptors (NLR) - cytosolic receptors which recognise both PAMPs and DAMPs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What do NOD1 and 2 do generally?

What does NOD2 detect

A

Recognise fragments of peptidoglycan from bacteria

Muramyl dipeptide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What releases NOD2

Why does it do this

What happens if NOD2 is mutated

A

Gut microbiota

NOD2 helps gut homeostasis

Mutations are associated with Crohn’s disease and IBS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

True or false

The NLR NLRP3 is specific to only one molecule

A

False

It has a wide specificity recognising pieces of peptideoglycan, bacterial DNA, ATP, toxins, ds-RNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What is the large cytosolic structure formed by NLRP3

A

The inflammasome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Name three disease is associated with the inflammasome

A

Atherosclerosis, gout, Type II diabetes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

How does the inflammasome induce inflammation

A

Activating casp-1 which stimulates IL-1β

28
Q

Why is casp 1 different to other caspases

A

It is involved with inflammation rather than apoptosis

29
Q

What are DAMPs usually

A

Intracellular molecules that appear in the wrong location, often after necrosis

DAMPs are associated with sterile inflammation

30
Q

Give some examples of DAMPs

A

Proteins from chromatin (HMGB-1)

Molecules eg ATP, DNA, RNA

Heat shock proteins

ECM components uncovered by tissue damage

31
Q

Which molecule involved in atherosclerosis is recognised by TLR4/TLR6

A

Oxidised LDL

32
Q

What Is the purpose of the acute inflammatory response

A

To dilute blood vessels

Increase permeability

Recruit cells

33
Q

Why does the acute inflammatory response increase permeability of the vessel wall

A

To allow a protein rich fluid into the tissues

A fibrin web forms and complement and CRP are recruited

34
Q

What do the granules in mast cells contain

How long does it take to release these

A

Histamine

Can be released in seconds

35
Q

What do you mast cells synthesise

How long does this take

A

Prostaglandins and leukotrienes

This takes some time (slow reacting substance of anaphylaxis (SRS-A))

36
Q

Mast cells have PRRs but how else can they be activated

A

By neurogenic information, responding to substance P released from nerve fibres

37
Q

What do you macrophages do at the site of infection?

A

Phagocytose microbes and produce a range of cytokines

Overall the response induces:
Vasodilation, vascular permeability and activation of endothelium leading to recruitment of the acute inflammatory exudate

38
Q

What produces endogenous pyrogens?

What type of molecule are they

A

Macrophages

Cytokines

39
Q

What do endogenous pyrogens from macrophages do (give a local and systemic effect)

A

They have local effects on the vascular endothelium and systemic effects such as acute phase protein response (IL-6)

40
Q

What are the four steps of recruitment of leucocytes to the site of infection

A

Rolling (weak tethering)

Tight adhesion

Diapedesis (extravasation)

Migration

41
Q

What is the rolling step of recruitment to the site of infection

A

Thrombin and histamine rapidly induce P-selectin on endothelial cells
E-selectin appears 1-2 hours later

The selectins bind to glycoprotein ligands (Sialyl Lewis X) present on the neutrophil

42
Q

Describe the affinity between selectin and the glycoprotein ligands on the neutrophil

A

These are low affinity interactions that break easily by the force of blood flow resulting in the rolling of cells along with the endothelium

43
Q

Where is P-selectin released from

A

Weibel- Palade bodies (intracellular stores in endothelial cells

44
Q

Which cytokines induce E-selectin release

Where are these cytokines derived from

A

IL-1 and TNF-α

Tissue macrophages

45
Q

What are the names of the glycoprotein ligands present on neutrophils

A

Sialyl Lewis X

46
Q

What does tight binding of neutrophils result from

A

Interaction between integrin family adhesion molecules (LFA-1) bonding to Ig super family molecules (ICAMs) on the endothelium

47
Q

What are ICAMs

A

Intercellular Adhesion Molecules

48
Q

Why is CXCL8 important in the tight adhesion step of recruitment of leukocytes to sites of infection

A

Initially interactions are weak but signalling through chemokine receptors (like CXCL8) causes a conformational change in LFA-1, resulting in a high binding affinity state

49
Q

What are the following associated with

a) ILC1
b) ILC2
c) ILC3

A

a) IFNγ
b) asthma
c) IBS

50
Q

Describe the diapedesis stage of leukocyte recruitment

A

leukocytes squeeze through the gaps between endothelial cells (extravasation) into the tissues.

This involves interactions between LFA-1 and CD31 on the endothelial cell. The neutrophil secretes enzymes (e.g. elastase) that degrade the basement membrane.

51
Q

Describe the migration stage of leukocyte recruitment

A

neutrophil then follows a gradient of CXCL8 to the site of infection

52
Q

How is the CXLC8 gradient used in leukocyte recruitment created

A

CXCL8 secreted by activated macrophages sticks to extracellular matrix in the tissues

53
Q

Give a disease related to leukocyte recruitment

A

Leukocyte adhesion deficiency (LAD); a rare immunodeficiency caused by a defect in the recruitment of neutrophils. LAD1 is caused by a defect in CD18, the b-chain subunit of LFA-1.

It results in recurrent life-threatening bacterial infection in infants. An identical condition is seen in cattle BLAD (Bovine Leukocyte Adhesion Deficiency).

54
Q

When are monocytes recruited to the site of inflammation cf. neutrophils

A

Monocytes are recruited later because the interaction involving endothelial adhesion molecule (VCAM-1), which binds to monocyte integrins (VLA-4, very late antigen-4) is upregulated more slowly (24 hours).

55
Q

What stops local infections entering the blood

why might infection be able to spread

A

Blood clotting and local expression of TNF-a

if infection is widespread, as in severe burns where there is loss of skin, infection can spread. Endotoxins such as LPS can provoke widespread TNF-a release.

56
Q

When does sepsis occur

A

when pathogens enter the blood stream. Macrophages in the liver and spleen secrete TNF-a into the circulation.

57
Q

What can be the consequences of sepsis

A

can be catastrophic as the vasodilation and movement of fluid into the tissues, triggered in part by TNF-a, contributes to loss of blood pressure,
a state that can progress to septic shock and heart failure.

released TNF-a also triggers blood clotting in the small vessels throughout the body (disseminated intravascular coagulation).

Failure of major
organs can occur due to loss of normal blood
perfusion.

Massive consumption of clotting proteins leads to lack of clotting capacity in the blood and bleeding.

58
Q

How does acute inflammation usually stop (3)

A

Many inflammatory mediators have short half-lives (neutrophils apoptose after few hours)

lipid mediator class–switch:
Instead of macrophages producing pro-inflammatory leukotrienes from arachidonic acid, the lipoxygenase system switches to producing anti-inflammatory lipoxin

switch to anti-inflammatory cytokines such as IL-10 and TGF-b

59
Q

What triggers the switch to turn off inflammation

A

triggered by engulfment of apoptotic neutrophils by macrophages.

60
Q

What is granulation tissue

what does this involve

A

After cell damage an attempt will be made to replace the dead tissue with healthy cells

essentially involves the recruitment of endothelial cells to form new blood vessels and fibroblasts to lay down extracellular matrix (ECM). The ECM is then remodelled to form strengthened scar tissue

61
Q

Which cells are pivotal to controlling repair after inflammation

A

macrophages

62
Q

Give 5 roles of macrophages in healing after inflammation

A

They phagocytose debris including RBCs, apoptotic neutrophils, dead organisms etc.

They produce reactive oxygen intermediates and nitric oxide to kill
microbes.

They recruit fibroblasts (FGF, fibroblast growth factor) which lay down new ECM

They recruit endothelial cells (VEGF) to form new blood vessels

They secrete metalloproteinases to allow remodelling of ECM

63
Q

How are fibroblasts involved in repair and healing - recruitment and role

A

recruited to the site of injury by cytokines (FGF) produced by
macrophages.

They are induced to increase collagen synthesis and produce other ECM proteins eventually leading to the formation of a collagen scar.

64
Q

How do vessels recently created by angiogenesis acquire endothelium

A

Endothelial cells break off from the basement membrane of pre-existing vessels, migrate to the site of injury and repair, proliferate and then differentiate to form a lumen and acquire supporting pericytes and smooth muscle to form the mature vessel.

65
Q

What can result in chronic inflammation (4)

A

Injurious agent may be endogenous: e.g. stomach acid (peptic ulcer)
Injurious agent may be non-degradable: e.g. silica, dust particles
Injurious agent may evade host defences: e.g. tuberculosis
Host may attack self components (autoimmunity): e.g. rheumatoid arthritis

66
Q

Which cells are important for chronic inflammation

what do they do

A

macrophages

Chronically activated macrophages accumulate releasing cytokines that stimulate proliferation of fibroblasts and collagen production- fibrosis

67
Q

Use an example to demonstrate granuloma formation

A

Mycobacteria can resist killing by macrophages.

They are not eliminated by the immune response but ‘walled off’ from surrounding tissue.

The central core of macrophages is surrounded by T cells.

Macrophages may fuse to become multinucleate giant cells or appear as large epithelioid cells. The central core is often necrotic.

BoD (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions