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intro to biomedical sciences IBMS > Inflammation part 2 > Flashcards

Inflammation part 2 Flashcards

1
Q

what are the 5 steps of the inflammatory response

5 RS

A 
recognition of injurious stimulus 
recruitment of leukocytes 
removal of the causative agent
regulation of the response
resolution of the response and repair
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2
Q

what is the first line of defence in recognising different pathogen

A

macrophages and dendritic cells

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3
Q

how many kinds of receptors do dendritic and macrophage cells have

A

several different types to recognise different pathogen associated molecular patterns (PAMPS)

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4
Q

what does PAMPS stand for

A

pathogen associated molecular patterns

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5
Q

what are TLRs

A

toll like receptors- a class of proteins which recognises PA,PS

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6
Q

what are TLRs made from

A

multiple leucine rich repeats

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7
Q

where are TLRs found

A

membrane associated proteins- some are found on the surface and some are endocytic vesicles

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8
Q

what do the endocytic TLrs detect

A

where they survey degraded particles of substances taken in by endocytosis

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9
Q

what does TLR5 recognise

A

flagellin- highly conserved constituent of bacterial flagella

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10
Q

what do bacterial genomes contain

A

highly methylated CPG oligonucleotides MOTIFS

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11
Q

what does TLR9 detect

A

highly methylated CPG oligonucleotides MOTIFS once it has been degraded in the lysosome

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12
Q

where is TLR9 found

A

in the endocytic vesicle

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13
Q

what TLRS are a dimer

A

TLR2 + TLR6

TLR1 +TLR2

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14
Q

what does TLR2 and TLR6 detect

A

diacylipopeptide

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15
Q

what do TLR1 and TLR2 detect

A

triacylipopeptide

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16
Q

what does TLR4 detect

A

lipopolysaccharide- found in gram -ve bacteria

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17
Q

where is TLR3 AND TLR7 found

A

inside the endocytic vesicle

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18
Q

what does TLR3 recognise

A

double stranded RNA

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19
Q

what does TLR7 recognise

A

single stranded RNA

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20
Q

What happens when TLR is activated

A

it sends a signal to the nucleus which activates transcription factors

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21
Q

where do viruses exist and replicate

A

in the cytosol

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22
Q

what are the two classes of receptors which recognise pathogens in the cytosol

A

NOD- nucleotide oligomerazation domain proteins

RNA helices domain and caspase recruitment domain- more importantly RIG-I

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23
Q

what does the NOD2 protein detect

A

bacterial proteoglycans of intracellular bacteria

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24
Q

what happens when the NOD2 receptor recognises its ligand

A

sends a signal to nucleus to activate transcription

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25
Q

what is the ligand of the NOD2 protein

A

muramyl dipeptide

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26
Q

what does RIG-I detect

A

double stranded rna which sends a signal to the nucleus

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27
Q

what happens when RIG-I is activated

A

sends a signal to the nucleus to produce type 1 interferon

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28
Q

what re the functions of a leukocyte

A

phagocytosis
secretion of microbicidal substances to remove extracellular inflammatory agent
release of extraceullar tramps eg NETosis
amplification of inflammatory response

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29
Q

what is NETosis

A

neutrophil-death through a different pathway than apoptosis or necrosis.

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30
Q

what can the secretion of microbicidal substances to remove extracellular inflammatory agent lead to

A

tissue damage

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31
Q

what is the key function of macrophages

A

to secrete pro inflammatory cytokines which then recruit further cells at the site of inflammation

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32
Q

what are the key players in amplification of inflammatory response

A

macrophages

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33
Q

what is NET

A

neutrophil extracellular traps

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34
Q

what is phagocytosis

A

recognition and attachment
engulfment
killing and degradation

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35
Q

what are microbes or dead cells recognised by in phagocytosis

A

direct or by opsonins

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36
Q

how does killing and degradation occur

A

by enzyme degradation and products of respiratory burst such as NO AND ROS

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37
Q

what is ROS in phagocytosis

A

reactive oxygen species

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38
Q

what is at the respiratory burst

A

a burst of activity where you get ROS AND NO into the intracellular space which are toxic molecules helps to kill pathogens

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39
Q

what is superoxide produced from

A

the oxidation of NADPH carried out by phagocyte oxidase

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40
Q

which enzyme carries out the oxidation of NADPH

A

phagocyte oxidase

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41
Q

what can superoxide be covered to

A

hydrogen peroxide and then hypochlorite by myeloperoxidase

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42
Q

what enzyme converts super chloride into hydrogen peroxide and hypochlorite

A

myeloperoxidase

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43
Q

WHERE IS MYELOPEROXIDASE FOUND

A

in cells with the myeloid lineage

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44
Q

what produces peroxynitrite

A

superoxide and nitric oxide

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45
Q

what can ROS cause

A

killing microbes but can also damage host cell injury

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46
Q

what is the pathological effects of ROS

A

LIPID PEROXIDATION- membrane damage
PROTEIN MODIFICATIONS- breakdown and misfolding
DNA DAMAGE leading to mutations

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47
Q

what enzymes are secreted from neutrophils azurophilic granules

A

neutrophil elastase
proteinase 3
cathespin G

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48
Q

WHAT EXTRACELLULAR ACTIVITY CAN OCCUR

A 
Secretion of microbicidal substances:
Secretion of enzymes 
release of lysosomal enzymes 
secretion of chemokines and cytokines 
NETosis
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49
Q

what is NETosis

A

the generation of neutrophil extracellular traps

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50
Q

what is NETosis stimulated by

A

microbes and inflammatory signals

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51
Q

what are the traps made from

A

nucleosomal DNA complex with histones which extrudes and produces a dense net of fibres which helps trap pathogens and materials

52
Q

what does the trap also contain

A 
lots of degrataive proteins such as myeloperoxidase 
cathepsin G 
elastase 
and LL37
Proteinase 3
53
Q

what can end up happening to the neutrophil once they have released the trap

A

they die in the process

54
Q

how does NETosis occur

A
  1. neutrophil is stimulated and results in the formation of NADPH oxidase and ROS production
  2. PAD4 is activated and the nuclear chromatin decondenses and the nuclear envelope loses its integrity
  3. NUCLEAR MATERIAL FILLS THE CELL AND MIXES WITH GRANULE CONTENT
  4. the plasma membrane ruptures and the nuclear chromatin associated with proteinases and histones is released into the extracellular space
55
Q

what is PAD4

A

peptidyl arginine deiminase 4

56
Q

what is responsible for the decondensation of the nuclear chromatin

A

PAD4- as it alters arginine AA in our histone complexes and changes them into another amino acid- citrulline

57
Q

where has large quantities of NET been found

A

in purulent GCF exudate in periodontitis

58
Q

what charge does arginine have

A

+vely charged AA

59
Q

how does PAD4 alter the histone complex

A

as it alters arginine AA in our histone complexes and changes them into another amino acid- citrulline

60
Q

what charge does citrulline have

A

neutral charge- change of electrostatic charges leads to the decondensation of nuclear chromatin

61
Q

what enzyme degrades the NET

A

Serum nucleases

62
Q

how is the net degredades

A

by serum nucleases and then macrophages dispose of the remaining net fragments

63
Q

how do auto antibodies form

A

when all the net hasn’t been degraded which can eked to auto immune diseases such as RA

64
Q

what are cell derived chemical mediators of inflammation

A 
vasoactive amines 
arachidonic metabolites 
cytokines and chemokine 
lysosomal enzymes 
NO 
ROS
65
Q

what are included in vasoactive amines

A

such as histamine/ seratonin which is found in granules

66
Q

what does histamine do

A

vasodilation and vascular permeability

67
Q

what are included in arachidonic metabolites

A

prostaglandins and leukotrienes

68
Q

what are included in cytokines and chemonkines

A

TNF
IL1
IL6
CXCL8

69
Q

what do arachidonic metabolites

A

vascular reactions and chemotaxis

70
Q

what do cytokines and chemokine

A

leukocyte recruitment

71
Q

give examples of lysosomal enzymes

A

Neutrophril elastase
Protinase 3
Collagensae
CG

72
Q

what do lysosomal enzymes do

A

microbicidal and tissue injury

73
Q

what are plasma protein derived chemical mediators of inflammation

A

complement proteins
coagulation proteins
kinins

74
Q

what are coagulation proteins triggered by

A

activated factor XII

75
Q

what is factor XII also known as

A

Hageman factor

76
Q

how are plasma protein derived species released

A

they are released as zymogens and then are proteolytically cleaved to release the activated form when closer to the site

77
Q

how are ROS removed

A

by anti oxidant molecules

78
Q

which molecules induce the acute phase response

A

IL-1 beta
IL6
tnf alpha

79
Q

what is a common blood test to see if people have an infection

A

is to check their serum CRP level

80
Q

what molecules initiate the acute phase response WHICH HAVE SYSTEMIC EFFECTS

A

TNF
IL6
IL1

81
Q

what do TNF, IL1.IL6 activate in the liver

A

acute phase proteins such as C reactive proteins

mannose binding lectin

82
Q

what does the activation of C reactive protein and mannose binding lectin lead to

A

activation of complement opsonisation

83
Q

what do TNF, IL1.IL6 activate in the bone marrow endothelium

A

neutrophil mobilisation

84
Q

what does the activation of neutrophil mobilisation

A

phagocytosis

85
Q

what do TNF, IL1.IL6 activate in the hypothalamus

A

increased body temp

86
Q

what does increased body temp lead to

A

decreased viral and bacterial replication
increased antigen processing
increased specific immune response

87
Q

what do TNF, IL1.IL6 activate in the fat muscle

A

protein and energy mobilisation to allow the increased body temperature

88
Q

what do TNF, IL1.IL6 activate in the dendritic cells

A

TNF alpha stimulates migration to the lymph nodes to maturation

89
Q

describe the CRP molecule

A

it is a pentraxin molecule and is a 5 sided shape

acts as an opsonin and activates complement

90
Q

what are acute phase protein examples

A

CRP

mannose binding lectin

91
Q

how are acute phase proteins released by the liver in relation to C reactive protein

A
  1. bacteria induce macrophages to produce IL6 which acts on hepatocytes to induce synthesis of APP
    THIS CAN LEAD TO
    C reactive proteins binds phosphocholine on bacterial surfaces acting as opsonin and activating complement
92
Q

how are acute phase proteins released by the liver relating to mannose binding lectin

A

binds to mannose residues on bacterial surfaces acting as opsonins

93
Q

what is involved in the family of leukotrienes

A

leukotriene A4
Leukotriene C4
leukotriene D4
leukotriene E4

94
Q

what do Leukotriene C4, leukotriene D4, leukotriene E4 cause

A

brochospasm

and increased vascular permeability

95
Q

what does prostacyclin PGI2 cause

A

Vasodilation and inhibit platelet aggregation increases fever and pain

96
Q

what does thromboxane TXA2 cause

A

vasoCONSTRICTION and promotes platelet aggregation

97
Q

what does cyclooxrgenase branch off into

A

prostaglandin G2—-> Prostagladin H2——> then to prostacyclin and thromboxane

98
Q

where does the leukotriene family start from

A

arachidonic acid metabolising into 5 lipoxygenase

99
Q

what are the two major branches of arachidonic acid metabolism

A

cyclooxygenases eg COX1 + COX2

5 lipoxygenase

100
Q

what is the key pathway for arachidonic acid metabolism in neutrophils

A

the 5 lipoxygenase pathway

101
Q

how are lipoxins A4 AND b4 formed

A

from the metabolism of 5 lipooxygenase into 12 lipoxygenase which then branches off into lipoxin A4 and lipoxin B4

102
Q

what does Lipoxin A4 AND B4 DO

A

inhibits neutrophil adhesion and chemotaxis

103
Q

what is the cyclooxygenases pathway inhibited by

A

anti inflammatory drugs non steroidal such as aspirin ibuprofen

104
Q

how did we think that the resolution of the response and repair occurs

A

due to the loss of mediators and the signal switches off for inflammation but we NOW KNOW THIS IS NOT ENOUGH

105
Q

what type of reaction is the resolution of inflammation

A

active regulated process

106
Q

how does a tissue return to health state of homeostasis

A

a programme of initiation must be activated

107
Q

what re the mediator molecules in acute inflammation

A 
pro inflammatory cytokines and chemokine 
histamin
prostaglandin 
leukotrienes 
thromboxane
108
Q

what are the mediators in resolution

A 
immunoresolvent such as 
IL10 
Resolvins 
lipoxins 
protectins
maresins
109
Q

what is chronic inflammation

A

refers to an inflammatory response of prolonged duration, in which the following proceed simultaneously:
continuing inflammation
tissue injury caused by WBC
attempts at repair (often by fibrosis and angiogenesis)

110
Q

what is fibrosis

A

the formation fibroblast cells in damaged tissue which generate connective tissue

111
Q

what are the damaged specialised cells replaced with

A

non specialised cells so it can change the function of the tissue which is not a good thing

112
Q

why might chronic inflammation occur

A

persistent infections
immune mediated inflammatory disease
prolonged exposure to toxic agents

113
Q

key characteristics of chronic inflammation

A

Mononuclear cell infiltrate- macrophages
Tissue destruction
Granulomatous tissue
Fibrosis

114
Q

what are the key features of acute inflammation

A

predominately neutrophils

115
Q

what [athology might be present in dental abscesses

A

both chronic and acute inflammation

116
Q

can chronic inflammation be present from the outset

A

yes for example RA where people have genetic predisposition for it

117
Q

how are macrophages split up

A

they can be pro or anti inflammatory depending on how they are activated aka classically activated macrophage or alternatively activated macrophage RETROSPECTIVELY

118
Q

what is IFN- gamma produced by

A

TH1C4 cell

119
Q

how is the macrophage activated in the presence of IFN- gamma and microbes

A

classically activated macrophage M1

120
Q

how is the macrophage activated in the presence of IL13 AND IL4

A

ALTERNATIVELY activated macrophage M2

121
Q

what does the M1 macrophage release

A 
leading to microbicidal actions: 
ros
no 
lysosomal enzymes
IL1 
IL2 
IL23 
chemokines
122
Q

what is IL13 AND IL4 produced by

A

TH2 cell

123
Q

what does the M2 macrophage produce

A

growth factors and TGF beta

and IL10

124
Q

what does TGF beta do

A

anti inflammatory effects and tissue repair

125
Q

what type of action occurs between the lymphocytes and macrophages

A

bidirectional

126
Q

what are the links between periodontitis and other diseases

A

athersclerosis
diabetes
RA
inflammation induced pregnancy complication

127
Q

what does P gingivalis have

A

a PAD enzyme leading to citrullinated histone complexes

intro to biomedical sciences IBMS (35 decks)

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