Inflammation 3 Flashcards
(131 cards)
1
Q
following invasion by pathogens get
A
immediate response (innate)
2
Q
innate response starts as soon as
A
pathogen enters
3
Q
how long does immediate innate response last
A
4 hours
4
Q
activation of what contributes to immediate innate response
A
adaptive pathway
5
Q
recognizing pathogen is job of
A
PRR (on epithelial cell, tissue macrophages, mast cells, etc)
6
Q
immediate innate response will rarely if ever result in
A
elimination of pathogen
7
Q
innate response will lead to what symptom
A
inflammation
8
Q
symptos of inflammation
A
fever
9
Q
macrophages secrete variety of mediators that promote
A
inflammatory response
10
Q
its possible pathogen may be eliminatedat which first stage
A
PRR and PAMP stage
11
Q
adaptive response can detect as early as
A
4-5 days
12
Q
when is adaptie response optimal
A
week after infection
13
Q
once t cells are generated in secondary lymphoid tissue what will have to do to contact the bad cells
A
go to site of infection
14
Q
inflammation exists to solve what problem
A
most infection is in tissue
the cells to fight (immune cells) are in circulation
want to get cells to the infected tissue
15
Q
describe of inflammation
A
vasodilation
more permeability
16
Q
inflammation can be innitated by
A
immune or non immuen stimulus
17
Q
first step in Immunological Steps in Inflammation
A
initiation
18
Q
describe initiation
A
trauma, tissue necrosis, infection or immune reaction
19
Q
what is second step in Immunological Steps in Inflammation
A
Acute Vascular Phase
20
Q
crucial for Acute Vascular Phase
A
activation of mast cells
21
Q
describe Acute Vascular Phase
A
release of vasoactive compounds from mast cells and macrophages leads to endothelial cell contraction and vasodilation and transudate release
22
Q
if non immune stimulas stop at what stage of step in Immunological Steps in Inflammation
A
stage 3
23
Q
if immune stimulus continue to what stage after stage 3 for step in Immunological Steps in Inflammation
A
Acute Cellular Phase
24
Q
describe Acute Cellular Phase
A
Chemotaxis, margination and emigration (transmigration/diapedesis) of neutrophils; diapedesis of erythrocytes. Resolution may occur at this stage if stimulus is adequately removed
25
chemotaxis is largely reuslt of production of
chemokines and other chemoattractants
26
chemokins promote neutrophils
halting on surface of endothelial cells
27
when leukocytes pull themselves through gaps b/w endothelial cells that step is called
diapedesis
28
neutrophils have to actiely do what thorugh gaps
pull themselves through
29
what is second to last step of Immunological Steps in Inflammation
Chronic Cellular Phase
30
acute dominated by
neutorphils
31
chronic inflammation dminated by
mononuclear cells → lymphocytes & monocytes
32
chronic cellular phase
Emigration of lymphocytes, infiltration by macrophage, emigration of eosinophils in parasitic infections or in allergic responses
33
what is last step in Immunological Steps in Inflammation
resolution
34
many mediators are already profiormed inside
mast cells
35
resolution stage has what two very important cytokines
IL 10
| TGF beta
36
IL-10 and TGF beta are what kind of cytokines
immunosuppressive
downregulate the inflammatory response
downregulate adaptive immune resopnse
37
some mediator srelease by mast cells stimulate contractino of
endothelial cells - so gap forms b/w endothelial cells
38
b/w endothelial gaps
leukocytes pull through to get to infected tissue
39
diaphedes of erythorcytes
why the infected are becomes red - vasodilation and RBC extravacating from cciruation into infected tissue
40
what are five cardinal signs of inflammation (or main 4 + fifth if severe)
```
Rubor – Redness
Tumor – Swelling
Calor – Heat
Dolor – Pain
Functio laesa – Loss of Function (only if severe)
```
41
describe the manifestation of signs of inflammation
immediate line of vasoconsturction then redness and vasodilation fo capillaries and arterioles. then swelling due to increase in vascular permeability due to endothelial cells pulling apart and fluid passing into the tissue
42
what is crucial to inflammation
mast cells
43
control of infiltration of inflammatory cells into tissue via
mast cells
44
how to activate mast cells
c3a and c5a
45
c3b and c4b are
opsinins
46
c3b and c4b allow leukocytes to
identify what it is they need to get rid of
47
c5a and c3a increas vascular
permeability → more complement proteins getinto complement tissue
48
bradyknin is main mediator that causes
pain
49
bradyknin induces an increase in
vascular permeability
50
c5a and c3a bind to receptors on mast cells and stimulate them to
degranulate - release contents fo their granules
51
mast cells also have PRR on their surface, so infectious agent by PAMPs binding can stimulate
mast cell degranulation
52
once mast cells stimulated to degranulate they will release
lots of pro-inflammatory mediators
53
what is released by mast cells
histamine
TNF alpha
IL-1
54
histamine is stored preformed in
mast cells
55
histamine induces
vasodilation
| increase in vascular permeability
56
affect of histamine is immediate but
short lived
57
what induces sustain in vascular permeability
TNF alpha and IL-1
58
TNF alpha and IL-1 induce iadhesion
on endothelial cells - so endothelial cells are sticky for other neutrophils. now neutrophils can grab on something to halt when they get to site of infection
59
inreas in vascular permeability allows plamsa proteins to seep from
cirulcaiton into tissue
60
bradyknin can stimualte degranulation of
mast cells
61
mast cells secrete what chemoattractant
IL-8 or (CXCL8)
62
all chemoattracts stimulate through
heterotrimeric G protein coupled receptors
63
mast cells secrete IL-8 and also release what lipid chemoattractant
LTB4
64
what is most potent chemoattractant for neutrophils
IL-8
65
mast cells are not the only cells activatied to initate leukocytes what else can be activated
activated by PAMPs binding to PRRs
66
activation of macrophages important b/c they are rich source of
pro-inflammatory ctokines
67
macrophages make
```
IL-1
TNF alpha
IL-6
IL-8
IL-12
```
68
IL-1
TNF alpha
IL-6 control what
acute phase response
69
IL-8 is a chemoattratant for
neutrophils
70
IL-12 activtes
natural killer cells
71
natural killer cells are important for killing spread of
viral infections
72
IL-6 is main factor responsible for
heat associated with acute inflammation
| induces fat and muscle metabolism which riases temp
73
IL-8 is
chemoattractant
74
IL-12 activates
NK cells
75
features of acute phase response
production of proteins importat for inflammation - so it repleneshes what we are using up
bone marrow endothelium - neutrophil mobilization "pus" mobilize the neutrophils from bone marrow and then attracted to site of infection by chemoattractants
hypothalamus - increase in body temp
IL-6 acts on fat and muscle for localized heat
76
mannose-bindin lectin
initator of ____ pathway
77
IL-1
TNF alpha
IL-6 are not
acute phase proteins, they just stimulate production of acute phase proteins
78
acute phase proteins also called
acute phase reactant
79
main function of acute phase response
replenishes what we are using up - like complement and neutrophils
80
acute phase response is regulated by
IL-1 IL-6 TNF alpha
81
IL-1 IL-6 TNF alpha act where
locally and distally - from bone marrow to hypothalamus to liver
82
acute phase proteins can limit
damage
83
name a very important representative of acute phase proteins
CRP (C reactive protein)
84
why are acute phase proteins important
cell surface or soluble PRRs
can measure them to get indication of repsonse to treatment
they will change their plasma concentration if there is inflammation or trauma going on
85
list the important acute-phase proteins
pg 66
86
suspect infection what test would you request
plasma or serum c-reactive protein
87
with activation of mast cells and release of chemoattractants calling out for
leukocytes - particarlly neutrophils
88
for neutrophils to get to infection
have to leave circulation and get to tissue
89
to get leukocytes migration need
chemoattractants
90
formylated peptides are characteristic of
bacteria
91
n-formlyated baterial peptides do what
chemoattractant
92
example chemoattractants to get leukocytes to site of infection
```
Examples:
N-Formylated bacterial peptides – FMLP
Complement derived – C5a, C3a
Lipid derived – Leukotriene B4 (LTB4)
Chemoattractant cytokines
Chemokines
e.g. - IL-8 (CXCL8), CCL5, CCL21
```
93
following exposure to chemoattract the leukocyte will migrate
to where the chemoattract is in highest concentration
94
chemotaxas
moving up the chemoattractant gradient
95
chemoattractans will stimluate what in neutrophil
to destory the pathogen once it takes it up
96
all chemoattracts ibnd to
7 pass membrane g protein coupled receptors
97
exposure of the neutrophil to chemoattractants results in increase in what
affinity of integrin for contrareceptor
98
four main families of chemokines
CXC chemokines
CC chemokines
(X)C chemokine
CX3C chemokine
99
chemokines classified on arrangement of
conservedn terminal cystein
100
CC chemokines have no intervening what the cysteins
no intervening aa
101
what is the clinical significance of chemokines in regards to HIV
CCR5 (M strain) CXCR4 (T strain)
102
chemokine receptors can bind more than one
chemokine
103
there is no numerical correlation b/w chemokine and
chemokine receptor - there is no correlation b/w what they bind to
104
single chemokine can bind to multiple
receptors
105
all chemokine receptors are
7 pass transmembrane g protein coupled receptors
106
for neutorphils to get from ciruclation into tissue have to do w=somethign to blood vessel endothelial cells, they have to adhere, the initial adherence is a very
low infinity interaction
107
the first reaction to endothelial cells is not sufficient
to stop neturophils b/c its so weak
108
normally endothelial cells are non inflamed and its not
sticky for neutrophils
109
during inflammation it induces expression of adhesion molecules onto
neutrophils - the endothelial cells slow down neutrophils
110
first cell into site of infection is
neutrophil
111
dominant leukocyte we have
neutrophil
112
four types of adhesion molecules to regulate immune cell intearaction to get to site of infection
addressins CD34
selectins - L-selectin
integrins - LFA-1
immunoglobulin like - ICAM-1
113
inital low affinity interactions of neutrophil and endothelial wall are b/w
addressins & selectins
114
when leukocytes arrive they will roll along surface of endothelial cells this is called
margination
115
rolling of leukocyte cell in cirulation is due to interaction b/w
adressin and selectins
116
adressin and selection interaction is not sufficient affinity to
bring neutrophil to a halt
117
what interaction brings neutrophil to a halt
integrin (LFA-1) and ICAM-1
118
when neutorphil arrives to ICAM-1 and binds the interaction isn't strong enough to get it through the endothelial cells - it then binds to CXCL8 and enduces
conformational change in LFA-1 to neutrophil and beocmes high affinity. the high affinity state is responsible for bringing neutrophil to halt on surface of endothelial cells
119
PECAM1 is located where
at junctions of individual endothelial cells
120
binding of neutrophils to PECAM-1 pulls it through the gaps of endothelial cells. ligand for PECAM-1 is
PECAM-1
121
once neutrophil comes to a haltthey will use what to pull them across the endothelial cell layer
PECAM-1
122
describe the 4 step model of extravastion of elukocyte into tissue
pg 81
123
diapedesis is what
crossing of blood vessel wall
124
by who and when are IL10 and TGF beta produced?
by macrophages
| produced towards end of inflammatory response
125
what are prostaglandins
lipid mediator that induces vasodilation
126
CXC chemokines strucrure
an aa b/w two cycsteins
127
(X)C chemokine structures
a single cys
128
CX3C chemokine structure
Cys-X-X-X-Cys
129
LFA-1 binds to
ICAM-1
130
what interaction brings the neutrophil to a halt
LFA-1 binding to ICAM-1
131
where is L selectin located
on neutrophil
