acute innate regeneration Flashcards
1
Q
what is acute inflammation?
A
response of living tissue to infection or damage
develops quickly
initiates innate immunity
2
Q
what are the 3 main processes if acute inflammation?
A
vascular dilation
increased vascular permeability
neutrophil activation and migration
3
Q
what are the 4 main causes of acute inflammation?
A
microbial infection
physical trauma
irritant or corrosive chemicals
tissue necrosis
4
Q
what are the 5 consequences of actor inflammation?
A
redness (rubor)
heat (calor)
swelling (tumor)
pain (dolor)
loss of function
5
Q
what causes redness in acute inflammation?
A
dilation of small blood vessels
6
Q
what causes heat in acute inflammation?
A
increased blood flow (hyperaemia)
7
Q
what causes swelling in acute inflammation?
A
accumulation of fluid in extra vascular space (oedema)
8
Q
what causes pain in actor inflammation?
A
stretching and distortion of the tissues due to oedema
chemical mediators induce pain
9
Q
what is an example of acute inflammation?
A
gingivitis
10
Q
what are the stages of acute inflammation?
A
initiation
progression
amplification
resolution
11
Q
at what stage does acute turn chronic inflammation?
A
no resolution of acute inflammation
12
Q
what happens in the initiation stage of acute inflammation?
A
microbes recognised by epithelium via TLR
13
Q
what happens in the progression stage of acute inflammation?
A
containment of microbes by innate immune cells and antimicrobial compounds (AMPs and IgA)
14
Q
what happens in the amplification stage of acute inflammation?
A
recruit and activate innate immune cells
via
-chemokine and cytokine activity
-vascular dilation
-increased vascular permeability
15
Q
what happens in the resolution phase of acute inflammation?
A
healing and repair
16
Q
what is the vascular response to acute inflammation?
A
- small blood vessels adjacent to damaged site become dilated
- endothelial cells swell and retract (promotes immune cell passage)
- exudation = vessels become leaky and water, salt, proteins pass
17
Q
what does leaky blood vessels in acute inflammation lead to? what is it?
A
oedema formation
= excess of watery fluid collecting in cavities or tissues
18
Q
increased lymph flow is oedema formation leads to what? what does this provide the tissue with?
A
inflammatory exudate forming
- fluids and salts
- glucose and o2
- complement proteins and antibodies
- fibrin
and immune cells
19
Q
what chemical mediators does oedema contain?
A
bradykinin
histamine
prostaglandins
20
Q
how is histamine made and where is it stored? what does it present as? what does it cause?
A
- breakdown of histidine
- stores in granules of mast cells
- neurotranmitter = itching
- vasodilation
21
Q
what produces prostaglandins?
what is the most abundant?
what is the main function?
A
- macrophages and neutrophils with leukotrienes
- prostaglandin E2
- vasodilation
22
Q
what drives prostaglandin production?
A
cycle-oxygenase ii
(COX II)
from macrophages and neutrophils
23
Q
what are the 4 proteolytic enzyme cascades?
A
complement system
kinin system
coagulation system
fibrinolytic system
24
Q
what is formed during the activation of the plasma factors?
A
enzyme complexes
protein cleavage
25
how are the plasma factors interconnected?
proteins produced in some systems lead onto other systems
26
what systems does coagulation factor XII activate?
kinin system
fibrinolytic system
coagulation system
27
what is another name for coagulation factor 12?
hageman factor
28
what are the 3 complement pathways? how are they initiated?
classical pathway = Antibodies attached to microbes
alternative pathway = microbial cell wall
mannose binding lectin pathway = carbs on pathogen surface
29
what are the 2 main outcomes of the complement pathway?
anaphylatoxins produced
membrane attack complex formed
30
what do anaphylatoxins do?
activate immune cells
induce permeability of blood vessels for recruitment of immune cells
31
what does the membrane attack complex do?
drives degradation of microbial cells
32
what is the protein in kinin system generated by coagulation factor 12?
kalikrein
33
what does kallikrein do?
converts kininogens to kinins eg bradykinin
34
what does Bradykinin do?
- increases permeability of blood vessels
- activates complement proteins
- induces immune cells to produce chemical and protein mediators
- pain via NS
35
what are the 3 pathways of the coagulation system?
intrinsic
extrinsic
common
36
what is the outcome of the coagulation system?
production of thrombin for clot formation
37
what does the fibrinolytic system result in?
activation of plasmin
38
what 2 proteins play a role in the fibrinolytic system? where from?
kallikrein from kinin system
hageman factor
39
what is the main function of plasmin?
breakdown fibrin to prevent excess blood clotting
40
how does plasmin activate complement?
cleaves C3
41
what is the indirect role of plasmin?
produce fibrin degradation products
to promote vascular permeability
42
what else drives conversion of plasminogen to plasmin? where is it found?
tPA on endothelial cells
43
give an example of a thrombolytic drug that drives the degradation of plasmin?
urokinase
44
what is haemostasis?
balance between coagulation and fibrinolytic systems (clotting to death vs bleeding to death)
45
what does haemostasis mean?
stop of blood flow
46
what are the 2 types of coagulation disorders?
congenital = haemophilia a or b
acquired = warfarin or heparin
47
what is a congenital coagulation disorder?
disease
48
what is an acquired coagulation disorder?
caused by drugs
49
what is it important to consider patients with coagulation disorders in dental surgery?
for example on extraction of tooth
wounds may take longer to heal or have complications
50
which outcome of acute inflammation can lead to chronic inflammation?
abscess formation (suppration)
51
what does abscess formation depend on?
tissue involved
amount of tissue destruction
nature of harmful agent
52
what type of inflammation leads to resolution and regeneration?
acute
53
what type of inflammation leads to repair?
chronic
54
what are the 3 types of dental abscesses?
gingival
periodontal
periapical
55
what is suppuration?
puss formation
56
what is pus?
bacteria with dead or dying neutrophils
57
what surrounds pus?
pyogenic membrane
58
what is the purpose of an abscess?
prevents spread of the bacteria or microbe
59
what does resolution require in acute inflammation?
- minimal cell death/tissue damage
- tissues must have regenerative capacity
- rapid elimination of causative agent
- rapid removal of fluid and debris by vascular/lymphatic drainage
60
what is innate immunity?
first ling of non specific response that responds to any microbial threat
61
what is tissue homeostasis?
balance between protection and destruction as the immune system encounters microbes daily
62
when does innate immunity occur?
hours to 4 days
63
what is a disadvantage of the innate immune response?
it has no lasting protective immunity
64
why is the innate immune system effective?
as it has regular contact with potential pathogens and destroys them quickly so they rarely cause disease
65
what are the 3 components of innate immunity?
epithelium (structural and mechanical support)
innate immune subset and complement
chemokines and cytokines
66
what do epithelial barriers and the oral cavity produce in saliva?
antimicrobial peptides
immunoglobulins IgA
lactoferrin
lysozyme
cystatins
67
what are major families of antimicrobial peptides?
b defensives
humans neutrophil peptides
68
name 2 roles of antimicrobial peptides?
modulate host immunity
directly kill microbes
69
what does SIgA do?
secretory piece = absorb saliva forming protective layer
dimeric form = attaches to multiple microbes
70
what does lactoferrin do?
transports ions
71
what is lysozyme?
targets cell wall or bacteria
72
what is crystatins?
antiprotenase activity and supports remineralisation of teeth
73
what are the main receptors in innate immune cells?
Toll like receptors
74
what are TLR primarily for?
bacterial and viral recognition
75
name 3 other types of microbial recognition receptors in innate immune system?
what is each for?
1. dectin and glucan = fungi
2. NOD-Like = bacterial
3. Protease-activated = microbial and allergen
76
what do Pattern recognition receptors recognise?
pathogen associated molecular patterns
77
what is the 3 signals in T cell differentiation?
1. antigen recognition
2. co-stimulatory receptors
3. cytokine tells T cell what to do
78
name 3 groups of cytokines? how is it decided?
interleukin family
TNF family
interferons
- depends on structure
79
what is autocrine signalling?
cell acting on cell it was secreted from
80
what is paracrine signalling?
cell acting on neighbouring cell
81
what is endocrine signalling?
enter circulation and alter behaviour of distant cell
82
what type of signalling can cytokines do?
autocrine
paracrine
endocrine
83
where are cytokine receptors and what do they recognise?
on target cell and recognise different cytokines
84
what happens if TLR or cytokine receptor recognises target?
downstream signalling cascade
different effector responses
85
what are chemokines?
chemotactic cytokines the direct cells to site of infection
86
what is chemotaxis?
move cell in direction corresponding to gradient of increasing or decreasing conc of particular substance
87
what is the main role of chemokines?
immune cell recruitment
88
what do chemokines and cytokines tell cell to do?
chemokine = where to go
cytokine = what to do
89
name examples of chemokine receptors?
CXC
C
CC
CX3C
90
how do we maintain tissue homeostasis?
pro inflammatory and anti inflammatory
chemokines/cytokines
91
what happens with immune over reaction?
autoimmune
allergy
92
what happens with immune under reaction?
infection
cancer
93
what are cytokines?
signalling molecules that coordinate immune response
94
what is the most abundant immune cell at the oral mucosa? what %
neutrophils 95%
95
what are neutrophils attracted along?
CXCL8 gradient (IL8)
96
how do neutrophils know where to go to get to infection?
cell adhesion molecules control attractions between immune cells and endothelial cells
97
what are the 3 families of cell adhesion molecules?
selections
integrins
immunoglobulin superfamily
- on different types of immune cells
98
what is the primary role of cell adhesion molecules?
immune cell trafficking and cell to cell interactions
99
what is the primary function of neutrophils?
engulf
destroy
degrade pathogens
100
how do neutrophils degranulate?
release granules once TLR have been activated
= release antimicrobial peptides and enzymes from vesicles
101
how do neutrophils produce NETS?
- once activated
- releases proteins and genetic material (chromatin)
- forms extra cellular fibril matrix
- traps pathogens
102
how are antimicrobials associated with NETs?
held whilst administered
103
what forms NETs?
chromatin
proteins
104
what are monocytes precursors for?
macrophages
105
when do monocytes differentiate into macrophages?
when they migrate to tissue
106
how do monocytes migrate to target tissue?
cell adhesion molecules
107
what are the 2 subsets of macrophages?
M1 = pro inflammatory
M2 = anti-inflammatory
108
what is the primary function of macrophage?
phagocytose and present antigen to adaptive immune cells
109
what do granules of granulocytes contain?
proteinases
antimicrobials
chemical mediators
110
what induced cells to degranulate?
M(P)AMPs
complement proteins
cytokines other inflammatory mediators
111
which cells phagocytose?
macrophages
neutrophils
dendritic cells
112
what is the 3 parts to phagocytosis?
degradation and removal of threat
antigen presentation
apoptosis
113
what are the 2 types of APC with examples?
nonprofessional = epithelial, endothelial, fibroblasts
professional = macrophage, dendritic cell
114
what is the steps of phagocytosis?
1. microbe ingested by phagocyte
2. formation of a phagosome
3. fusion of phagosome with lysosome = phagolysosome
4. digestion of ingested microbe by enzymes
5. residual body formed w indigestible materials
6. discharge of the waste material
115
what is antigen presentation?
interaction between MHC I or MHCII and the antigen then this complex is presented to T cell
116
what links the innate and adaptive immune system?
phagocytosis and antigen presentation
117
how much of blood does plasma make up?
55%
118
what kind of response is plasma factors?
humoral
119
what is complement?
soluble proteins in circulation that drives inflammation or opsonisation
120
what is opsonisation?
coating of pathogens by antibodies or complement proteins
121
if an antibody is attached to a microbe what complement pathway is activated?
classical
122
if complement proteins recognise the microbial cell wall what kind of complement is activated?
alternative
123
if carbs on pathogen surface are recognised by complement proteins which complement pathway is activated?
mannitose binding lectin
124
what 2 enzymes are produced in complement?
C3 and C5 convertase
125
what is the function of C3 and C5 convertase?
degradation of C3 and C5 proteins producing anaphylatoxins
126
what do anaphylaxis lead to?
SM contraction and capillary leakage therefor increased infiltration of immune cells to site of infection
127
how do anaphylatoxins promote immune cell recruitment?
- increases adhesion of cells to vessel wall
- induce granulation
- cytokine production
- antigen presentation
- regulate adaptive immune response
