2.5 Inflammation and adhesion Flashcards
1
Q
Stimuli for Inflammation
A
infection, truama, physical chemical agents, necrosis, foreign bodies, immune reactions (foreign and auto)
2
Q
features of inflammation
A
complex, nonspecific, mostly vascular and connective tissue reaction to injury, migration of leukocytes, systemic reactions, closely linked to immune system, coagulation system and repair process
3
Q
Goal of inflammation
A
to eliminate, dilute or wall off injurious agent, but can be very harmful
4
Q
inflammation overlaps with
A
immunity,
coagulation,
repair
5
Q
host resistance is divided into
A
innate and adaptive immunity
6
Q
coagulation system is divided into
A
dual function of clotting factors and factors as mediators
7
Q
usually inflammation leads to
A
induction of repair and repair inhibits inflammation. But not always resulting in disease
8
Q
inflammation time course can be
A
acute or chronic (granulomatous)
9
Q
5 cardinal signs of acute inflammation
A
rubor, tumor, calor, dolor, functio laesa
10
Q
rubor
A
redness
11
Q
tumor
A
swelling
12
Q
calor
A
heat
13
Q
dolor
A
pain
14
Q
functio laesa
A
loss of fn
15
Q
cells of inflammation
A
neutorphil, basophil, platelet, eosinophil, monocyte/macrophage, lymphocyte, plasma cell
16
Q
neutrophil
A
poly or PMN (many lobed nucleus) seen in acute inflammation
17
Q
basophil
A
accute/allergic - dark granules
18
Q
platelet
A
acute
19
Q
eosinophil
A
chronic/allergic
20
Q
monocyte/macrophage
A
chronic - kidney shaped nucleus
21
Q
lymphocyte
A
chronic - little bigger than a red cell
22
Q
plasmacell
A
chronic - eccentric nucleus filled with mrna for Ig
23
Q
difference btw eosinophil and mast cell
A
eosinophil will be red granules and mast cell will be purpleish
24
Q
band form
A
immature neutrophil looks like a wll defined horse shoe - not normal to have lots - tells you there is overproduction
25
other cells also important for inflammatory process
fibroblasts
26
simple demonstration of inflammatory response
wheal and flare reaction
27
first thing when you scrape arm
goes white due to vasoconstriction of arteries and arterioles
28
why does the white scratch turn red
you induced an inflammatory response so there is hyperemia as more blood rushes there
29
what governs efflux and influx of fluid in vessels
mediators - inflammation gets things out of the vessels where you need them,
they don_t have to be damaged and leaky bc the mediators will direct them
30
transudate
fluid accumulation in body cavity with low protein/specific gravity - ultrafiltrate - i.e. water squeezed out of vessels
31
exudate
fluid accumulation in body cavity with high protei/ specific gravity
32
edema
interstitial fluid accumulation (may be transudate or exudate)
33
purulent
pus
34
exudate in lungs
pneumonia
35
transudate in lungs
heart failure
36
duet to normal laminar flow and arterial and venou pressure
hydrostatic pressure forces fluid out and osmotic pressure draws fluid back in but only 80%. The other 20% goes to lymphatics
37
with increased flow during vasodialation you get
increased hydrostatic pressure and transudate
38
when endothelial cells get "leaky" you get
exudate - endothelial cells have increased permeability for proteins increasing the osmotic pressure
39
hemoconcentration and stasis
loss of lamnar flow, rolling, attachment, transmigration
40
factors affecting vascular permeability (leakage)
```
endothelial gap formation,
endothelial retraction,
increasaed trancytosis,
direct injury,
delayed prolonged leakage (like sunburn),
leukocyte-mediated damage,
leakage from new blood vessels
```
41
Endothelial gap formation
most common mechnaism of non damage active vascular leakage
42
endothelia gap formation is the major effecto of mediators such as
histamine, bradykinin, leukotrienes, substance P
43
where does endothelial gap formation occur
exclusively in post capillary venules of 20 to 60 um in diameter (receptor density)
44
how long does endothelia gap formation last
rapid and short lived - immediate transient response
45
cytoskeletal reorganization/endothelial retraction
cytoskeleton changes and endothelial cells retract from one another
46
how is endothelial retraction induced
by cytokines such as Il1 and TNF alpha or hypoxia and sublethal injury
47
how long does cytoskeletal reorganization take
endothelial retraction is delayed 4-6 hrs and lasts longer up to 24 hrs
48
is endothelial retraction localized
not perfectly localized bc injury can induce it
49
increased trancytosis
movement of fluid and material across endothelial cytoplasm, occurs through clusters of uncoated vesicles and vacuoles called the vesiculovacular organelle
50
how is trancytosis induced
vascular endothelial growht factor (VEGF) - also may be induced by histamine
51
Direct endothelial injury resulting in necrosis results in
leakage from damaged vessels, immediate and long lasting (immediate sustained response), happens in small and large vessels, and is associated with platelet aggregation and thrombosis
52
Delayed prolonged leakaged
2-12 hours lasting for hours to dayes, occurs at venules and capilaries
53
how is delayed prolonged leakage induced
by mild thermal burns, ionizing and UV radiation (sunburn--get pain not just on skin but all over, chills..)
54
delayed prolonged leakage mechanism
maybe apoptosis from DNA damage
55
leukocyte mediated damage
leukocytes adhere to activated or damaged endothelium, secrete reactive and toxic products that damage self as well as microbes, location dependent on why and where leukocytes bind
56
leakage from new blood vessels
during repair angiongenesis occurs and new vess are nleaky before new endothelial cells fully differentiate and form gap junctions, VEGF induces increased vascular permeability, new endothelium has an increased density of receptors for vasoactive signals
57
what allows for pure collection of white exudate (pus)
mediators allowing collection of neutrophoils - so don't need vessel trauma for inflammation
58
Margination
a hemodynamic effect where lamina flow of leukocytes changes to peripheral and contacto vascular wall duing stasis
59
rolling-adhesion-extravasation occurs by
modulating various adhesion molecules on the surface of endothelial cells and leukocytes
60
rolling-adhesion-extravasation is mediated by
secreated or formed inflammatory mediators
61
rolling-adhesion-extravasation strategies are to
increase the number of receptors and increase affinity of receptors for ligands
62
endothelium molecules
```
p-selectin,
e-selectin,
ICAM-1,
VCAM1,
CD 34/GlyCam,
CD31
```
63
P-selectin
sialyl-lewis X and PSGL-1 (rolling: N, M, L)
64
E -selectin
sialyl-lewis X (rolling adhesion: N, M, L)
65
ICAM - 1
CD11/18 (beta2 integrins, aka LFA1 and Mac-1) (adhesion, arrest and transmigration: all leukocytes)
66
Vcam-1
VLA4 (alpha4beta1) (integrins) and LPAM-1(alpha4beta7) (adhesion E,M,L)
67
CD-34/GlyCam
L-selectin (rolling; lymphocyte homing: L)
68
CD31 (PECAM)
CD31 (transmigration:all)
69
Selectins
have an extracellular sugar binding domain similar to lectins. They bind sialyated oligosaccharides
70
knock out L selectin
poorly formed LNs and few t cells
71
knock out either E or P selectin
mind effects bc the other compensates
72
knock out both e and p selectin
severe effects
73
immunoglobulin like molecules
ICAM-1, VCAM-1 (both bind integrins on leukocytes)
74
integrins
transmembrane heterodimer glycoproteins with alpha and beta chains
75
beta 2 integrins
LFA1 and MAC1 (bind ICAM1)
76
beta 1 integrins
VLA4 and LPAM1 (bind to VCAM1)
77
1. histamine, thrombin and PAF induce
the redistribution of P-selectin from intracellular sotres (weible-palade bodies) to the surface (takes minutes)
78
2. Tnf and IL1 induce
the synthesis of E-selectin ICAM1, VCAM1 (takes 1-2 hours)
79
3.luekocyte specific chemokines alter
conformation of LFA-1 and MAC-1 increasing the affinity of binding to ICAM 1.
requires ICAM1 and synthesis of chemokines by othercells (late response)
80
4. early endothelial activation i.e.
rolling (selectins and sialyl-lewis X)
81
5. later synthesis of
endothelial adhesion molecules and increased affinity of LFA1 and MAC1 --firm adhesion
82
7. CD31, ICAM and integrins result in
transmigration
83
genetic deficiency called leukocyte adhesion deficiency type 1 (LAD1)
def in LFA1 and Mac
84
LAD2
def in sialyl-LewisX - big problem with leukocyte accumulation
85
antibidies to adhesion molecules can block inflammation like
Natalizumab
86
natalizumab
humanized monoclonal AB to VLA4 (alpha4beta1interin) to treat MS
87
negative effect of natalizumab
bind up all the vla4? So no adhesion of leukocytes
