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
2
Q
what is the first line of defence in recognising different pathogen
A
macrophages and dendritic cells
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)
4
Q
what does PAMPS stand for
A
pathogen associated molecular patterns
5
Q
what are TLRs
A
toll like receptors- a class of proteins which recognises PA,PS
6
Q
what are TLRs made from
A
multiple leucine rich repeats
7
Q
where are TLRs found
A
membrane associated proteins- some are found on the surface and some are endocytic vesicles
8
Q
what do the endocytic TLrs detect
A
where they survey degraded particles of substances taken in by endocytosis
9
Q
what does TLR5 recognise
A
flagellin- highly conserved constituent of bacterial flagella
10
Q
what do bacterial genomes contain
A
highly methylated CPG oligonucleotides MOTIFS
11
Q
what does TLR9 detect
A
highly methylated CPG oligonucleotides MOTIFS once it has been degraded in the lysosome
12
Q
where is TLR9 found
A
in the endocytic vesicle
13
Q
what TLRS are a dimer
A
TLR2 + TLR6
TLR1 +TLR2
14
Q
what does TLR2 and TLR6 detect
A
diacylipopeptide
15
Q
what do TLR1 and TLR2 detect
A
triacylipopeptide
16
Q
what does TLR4 detect
A
lipopolysaccharide- found in gram -ve bacteria
17
Q
where is TLR3 AND TLR7 found
A
inside the endocytic vesicle
18
Q
what does TLR3 recognise
A
double stranded RNA
19
Q
what does TLR7 recognise
A
single stranded RNA
20
Q
What happens when TLR is activated
A
it sends a signal to the nucleus which activates transcription factors
21
Q
where do viruses exist and replicate
A
in the cytosol
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
23
Q
what does the NOD2 protein detect
A
bacterial proteoglycans of intracellular bacteria
24
Q
what happens when the NOD2 receptor recognises its ligand
A
sends a signal to nucleus to activate transcription
25
what is the ligand of the NOD2 protein
muramyl dipeptide
26
what does RIG-I detect
double stranded rna which sends a signal to the nucleus
27
what happens when RIG-I is activated
sends a signal to the nucleus to produce type 1 interferon
28
what re the functions of a leukocyte
phagocytosis
secretion of microbicidal substances to remove extracellular inflammatory agent
release of extraceullar tramps eg NETosis
amplification of inflammatory response
29
what is NETosis
neutrophil-death through a different pathway than apoptosis or necrosis.
30
what can the secretion of microbicidal substances to remove extracellular inflammatory agent lead to
tissue damage
31
what is the key function of macrophages
to secrete pro inflammatory cytokines which then recruit further cells at the site of inflammation
32
what are the key players in amplification of inflammatory response
macrophages
33
what is NET
neutrophil extracellular traps
34
what is phagocytosis
recognition and attachment
engulfment
killing and degradation
35
what are microbes or dead cells recognised by in phagocytosis
direct or by opsonins
36
how does killing and degradation occur
by enzyme degradation and products of respiratory burst such as NO AND ROS
37
what is ROS in phagocytosis
reactive oxygen species
38
what is at the respiratory burst
a burst of activity where you get ROS AND NO into the intracellular space which are toxic molecules helps to kill pathogens
39
what is superoxide produced from
the oxidation of NADPH carried out by phagocyte oxidase
40
which enzyme carries out the oxidation of NADPH
phagocyte oxidase
41
what can superoxide be covered to
hydrogen peroxide and then hypochlorite by myeloperoxidase
42
what enzyme converts super chloride into hydrogen peroxide and hypochlorite
myeloperoxidase
43
WHERE IS MYELOPEROXIDASE FOUND
in cells with the myeloid lineage
44
what produces peroxynitrite
superoxide and nitric oxide
45
what can ROS cause
killing microbes but can also damage host cell injury
46
what is the pathological effects of ROS
LIPID PEROXIDATION- membrane damage
PROTEIN MODIFICATIONS- breakdown and misfolding
DNA DAMAGE leading to mutations
47
what enzymes are secreted from neutrophils azurophilic granules
neutrophil elastase
proteinase 3
cathespin G
48
WHAT EXTRACELLULAR ACTIVITY CAN OCCUR
```
Secretion of microbicidal substances:
Secretion of enzymes
release of lysosomal enzymes
secretion of chemokines and cytokines
NETosis
```
49
what is NETosis
the generation of neutrophil extracellular traps
50
what is NETosis stimulated by
microbes and inflammatory signals
51
what are the traps made from
nucleosomal DNA complex with histones which extrudes and produces a dense net of fibres which helps trap pathogens and materials
52
what does the trap also contain
```
lots of degrataive proteins such as myeloperoxidase
cathepsin G
elastase
and LL37
Proteinase 3
```
53
what can end up happening to the neutrophil once they have released the trap
they die in the process
54
how does NETosis occur
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
what is PAD4
peptidyl arginine deiminase 4
56
what is responsible for the decondensation of the nuclear chromatin
PAD4- as it alters arginine AA in our histone complexes and changes them into another amino acid- citrulline
57
where has large quantities of NET been found
in purulent GCF exudate in periodontitis
58
what charge does arginine have
+vely charged AA
59
how does PAD4 alter the histone complex
as it alters arginine AA in our histone complexes and changes them into another amino acid- citrulline
60
what charge does citrulline have
neutral charge- change of electrostatic charges leads to the decondensation of nuclear chromatin
61
what enzyme degrades the NET
Serum nucleases
62
how is the net degredades
by serum nucleases and then macrophages dispose of the remaining net fragments
63
how do auto antibodies form
when all the net hasn't been degraded which can eked to auto immune diseases such as RA
64
what are cell derived chemical mediators of inflammation
```
vasoactive amines
arachidonic metabolites
cytokines and chemokine
lysosomal enzymes
NO
ROS
```
65
what are included in vasoactive amines
such as histamine/ seratonin which is found in granules
66
what does histamine do
vasodilation and vascular permeability
67
what are included in arachidonic metabolites
prostaglandins and leukotrienes
68
what are included in cytokines and chemonkines
TNF
IL1
IL6
CXCL8
69
what do arachidonic metabolites
vascular reactions and chemotaxis
70
what do cytokines and chemokine
leukocyte recruitment
71
give examples of lysosomal enzymes
Neutrophril elastase
Protinase 3
Collagensae
CG
72
what do lysosomal enzymes do
microbicidal and tissue injury
73
what are plasma protein derived chemical mediators of inflammation
complement proteins
coagulation proteins
kinins
74
what are coagulation proteins triggered by
activated factor XII
75
what is factor XII also known as
Hageman factor
76
how are plasma protein derived species released
they are released as zymogens and then are proteolytically cleaved to release the activated form when closer to the site
77
how are ROS removed
by anti oxidant molecules
78
which molecules induce the acute phase response
IL-1 beta
IL6
tnf alpha
79
what is a common blood test to see if people have an infection
is to check their serum CRP level
80
what molecules initiate the acute phase response WHICH HAVE SYSTEMIC EFFECTS
TNF
IL6
IL1
81
what do TNF, IL1.IL6 activate in the liver
acute phase proteins such as C reactive proteins
| mannose binding lectin
82
what does the activation of C reactive protein and mannose binding lectin lead to
activation of complement opsonisation
83
what do TNF, IL1.IL6 activate in the bone marrow endothelium
neutrophil mobilisation
84
what does the activation of neutrophil mobilisation
phagocytosis
85
what do TNF, IL1.IL6 activate in the hypothalamus
increased body temp
86
what does increased body temp lead to
decreased viral and bacterial replication
increased antigen processing
increased specific immune response
87
what do TNF, IL1.IL6 activate in the fat muscle
protein and energy mobilisation to allow the increased body temperature
88
what do TNF, IL1.IL6 activate in the dendritic cells
TNF alpha stimulates migration to the lymph nodes to maturation
89
describe the CRP molecule
it is a pentraxin molecule and is a 5 sided shape
| acts as an opsonin and activates complement
90
what are acute phase protein examples
CRP
| mannose binding lectin
91
how are acute phase proteins released by the liver in relation to C reactive protein
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
how are acute phase proteins released by the liver relating to mannose binding lectin
binds to mannose residues on bacterial surfaces acting as opsonins
93
what is involved in the family of leukotrienes
leukotriene A4
Leukotriene C4
leukotriene D4
leukotriene E4
94
what do Leukotriene C4, leukotriene D4, leukotriene E4 cause
brochospasm
| and increased vascular permeability
95
what does prostacyclin PGI2 cause
Vasodilation and inhibit platelet aggregation increases fever and pain
96
what does thromboxane TXA2 cause
vasoCONSTRICTION and promotes platelet aggregation
97
what does cyclooxrgenase branch off into
prostaglandin G2----> Prostagladin H2------> then to prostacyclin and thromboxane
98
where does the leukotriene family start from
arachidonic acid metabolising into 5 lipoxygenase
99
what are the two major branches of arachidonic acid metabolism
cyclooxygenases eg COX1 + COX2
| 5 lipoxygenase
100
what is the key pathway for arachidonic acid metabolism in neutrophils
the 5 lipoxygenase pathway
101
how are lipoxins A4 AND b4 formed
from the metabolism of 5 lipooxygenase into 12 lipoxygenase which then branches off into lipoxin A4 and lipoxin B4
102
what does Lipoxin A4 AND B4 DO
inhibits neutrophil adhesion and chemotaxis
103
what is the cyclooxygenases pathway inhibited by
anti inflammatory drugs non steroidal such as aspirin ibuprofen
104
how did we think that the resolution of the response and repair occurs
due to the loss of mediators and the signal switches off for inflammation but we NOW KNOW THIS IS NOT ENOUGH
105
what type of reaction is the resolution of inflammation
active regulated process
106
how does a tissue return to health state of homeostasis
a programme of initiation must be activated
107
what re the mediator molecules in acute inflammation
```
pro inflammatory cytokines and chemokine
histamin
prostaglandin
leukotrienes
thromboxane
```
108
what are the mediators in resolution
```
immunoresolvent such as
IL10
Resolvins
lipoxins
protectins
maresins
```
109
what is chronic inflammation
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
what is fibrosis
the formation fibroblast cells in damaged tissue which generate connective tissue
111
what are the damaged specialised cells replaced with
non specialised cells so it can change the function of the tissue which is not a good thing
112
why might chronic inflammation occur
persistent infections
immune mediated inflammatory disease
prolonged exposure to toxic agents
113
key characteristics of chronic inflammation
Mononuclear cell infiltrate- macrophages
Tissue destruction
Granulomatous tissue
Fibrosis
114
what are the key features of acute inflammation
predominately neutrophils
115
what [athology might be present in dental abscesses
both chronic and acute inflammation
116
can chronic inflammation be present from the outset
yes for example RA where people have genetic predisposition for it
117
how are macrophages split up
they can be pro or anti inflammatory depending on how they are activated aka classically activated macrophage or alternatively activated macrophage RETROSPECTIVELY
118
what is IFN- gamma produced by
TH1C4 cell
119
how is the macrophage activated in the presence of IFN- gamma and microbes
classically activated macrophage M1
120
how is the macrophage activated in the presence of IL13 AND IL4
ALTERNATIVELY activated macrophage M2
121
what does the M1 macrophage release
```
leading to microbicidal actions:
ros
no
lysosomal enzymes
IL1
IL2
IL23
chemokines
```
122
what is IL13 AND IL4 produced by
TH2 cell
123
what does the M2 macrophage produce
growth factors and TGF beta
| and IL10
124
what does TGF beta do
anti inflammatory effects and tissue repair
125
what type of action occurs between the lymphocytes and macrophages
bidirectional
126
what are the links between periodontitis and other diseases
athersclerosis
diabetes
RA
inflammation induced pregnancy complication
127
what does P gingivalis have
a PAD enzyme leading to citrullinated histone complexes
