Inflammation Flashcards
1
Q
-itis
A
suffix meaning inflammation
2
Q
what is the general mechanical cause of inflammation
A
when the mechanical barrier of the innate immunity is breached tissue injury induces a complex cascade of events that constitute inflammation
3
Q
Definition of inflammation
A
Defense reaction of living tissue against damage, aimed at removing the cause of injury and repairing the tissue
4
Q
which immune response does inflammation play a role in
A
both innate and adaptive immunity
5
Q
what are the types of inflammation
A
- Acute
- chronic
6
Q
-Acute inflammation
A
fights the early stages of infection and prepares the process that leads to tissue repair
7
Q
Chronic inflammation
A
is characterized by the dominating presence of macrophages in the injured tissue
8
Q
what are the three main exogenous causes of inflammation
A
- physical agent
- chemical agents
- Biological agents
9
Q
what are the main endogenous causes of inflammation
A
- Circulation disorders
- Metabolic products
10
Q
what are the 5 hallmark signs of acute inflammation
A
- calor
- rubor
- tumor
- dolar
- functio laesa
11
Q
Calor:
A
heat
12
Q
Rubar:
A
redness
13
Q
Tumor:
A
swelling
14
Q
Dolar:
A
pain
15
Q
Functio laesa:
A
loss of function
16
Q
how does vasodilation affect lead to inflammation
A
-vasodilation increases the blood flow to the injured area rising the temp (heat/calor)
17
Q
how does large volumes of blood contribute to inflammation
A
-large amounts of blood in the area of injury cause hyperaemia (redness/rubar) of the area of injury
18
Q
how does vascular permeabiltiy increase lead to inbflammation
A
this leads to fluid leaking from the blood vessels into the area of injury.
- this fluid accumulation leads to oedema (swelling/tumor)
19
Q
how do leukocytes contribute to inflammation
A
- within a few hours leukocytes adhere to the endothelium in the injured area leading to extravasation
- the leukocytes phagocytose invading pathogens and release mediators that further contribute to inflammation
20
Q
What are the mediators that are released by the leukocytes responsible for
A
they are responsible for such things as pain(Dola) in the area of injury
21
Q
Inherently with an injury the are affected losses _____
A
function/Functio Laesa
22
Q
what are the pro-inflammatory cytokines
A
- TNFalpha
- IL-1
- IL-6
- IL-8
23
Q
TNFalpha:
A
tumor necrosis factor alpha
24
Q
TNFalpha and IL-1 induce
A
- fever
- stress hormone production
25
what stress hormones do TNFalpha and IL-1 induce
- norepinephrine
| - vasopressin
26
what do norepinephrine vasopressin hormones induce
-activations of the RAAS system (Renin-angiotensin-aldosterone system)
27
what other signaling molecules does TNFalpha and IL-1 induce synthesis of
- IL-6
- IL-8
- IFNy
28
IL-6 stimulates the release of _____ such as
- acute phase proteins
| - C-reactive protein (CRP)
29
The proinflammatory cytokines activate the _______ cascade,release of _____, ____________, __________, and ________
The proinflammatory cytokines activate the coagulation cascade, release of nitric oxide, Platelet-activating factor, prostaglandins, and leukotrienes
30
which interleukins promote chemotaxis, induce extravasation of granulocytes and degranulation of neutrophils
- IL-1
- IL-6
- IL-8
31
what complement components increase vascular permeabiltiy
- C3a
| - C5a
32
Complement components C3a and C5a stimulate ______ of neutrophils, eosinophils, and monocytes
chemotaxis
33
what is prostaglandins
lipid soluble molecules derived from arachidonic acid
34
________ contributes to vasodilation, capillary permeability, pain and fever during inflammation
Prostaglandins
35
how do prostaglandins affect BP
it lowers BP
36
how do stable prostaglandins (PGE1 and PGE2) effect histamine and other inflammatory mediators
PGE1 and PGE2 potentiate the effects of histamine and other inflammatory mediators
37
Prostaglandin thromboxane A2 promotes___________ and __________
- platelet aggregation
| - vasoconstriction
38
what are leukotrienes
eicosanoid inflammatory mediators produced in leukocytes by the oxidation of arachidonic acid
39
what are the 4 leukotrienes we are concerned with
- LTB4
- LTC4
- LTD4
- LTE4
40
LTB4 is:
a potent chemoattractant of neutrophils
41
Vasoactive amines:
-histamines and serotonin
42
where are vasoactive amines found in high conc.
- in platelets
- basophils
- mast cells
43
what do vasoactive amines cause
-dilation and increased permeability . of capillaries
44
which receptors do the vasoactive amines act through
- H1 (histamine)
| - 5-HT (serotonin)
45
PAF:
Platelet-activating factor
46
PAF is generated from
-lipid complex stored in cell membranes
47
what is the function of PAF
it affects many cell types and induces platelet aggregation
48
what cells do PAF activate
neutrophils
49
what cell treats PAF as a potent chemoattractant
eosinophils
50
how does PAF contribute to edema
-it contributes to exflux of plasma proteins leading to edema
51
what are the two main types of plasma proteases
- Kinins
| - Clotting factors
52
what is the function of Kinins
-particularly bradykinin- increase capillary permeability (a role in hyperthermia and redness) and pain
53
what is the function of clotting factors
-Production of fibrin peptides during the final steps of the clotting process
54
What are the 2 important stages of inflammation
- vascular
| - cellular
55
what triggers the vascular and cellular stages of inflammation
the entry of a pathogen in healthy tissues of the body
56
the vascular response phase 1
- vasoconstriction
- momentary constriction of small blood vessels in the area
- begins 30-sec post-injury and lasts a few mins.
57
the vascular response phase 2
- Active vasodilation
- Dilation of arterioles and capillaries (redness=rubar)
- increase in blood flow
- Active hyperemia in inflamed region and increased cellular metabolism leading to higher local temp (heat=colar)
58
the vascular response phase 3
- passive vasodilation
- bloodvessels stop reacting to nervous and humoral stimuli
- increase in vascular permeability causes swelling (tumor), pain, and impaired function (functio laesa)
59
what is the cellular response to an injury
- marked by the movement of leukocytes into the area of injury
- mainly granulocytes and monocytes
60
The cellular response phase 1
- chemotaxis
| - Leukocytes migrate in response to a chemical signal
61
The cellular response phase 2
- Rolling
| - leukocytes slow down and increase their epression of adhesion molecules
62
The cellular response phase 3
- Migration
| - migrate into the tissue spaces
63
The cellular response phase 4
- Phagocytosis
| - Neutrophils and macrophages engulf and degrade the bacteria and cellular debris
64
what are the first cells to arrive at the site of injury
- cells of innate immunity (granulocytes, neutrophils, M(phi), NK)
- AKA Leukocytes
65
how long does it take for the immune system to react after an injury
the immune system reacts immediately after an injury
66
what is another name for the migration of leukocytes to sites of infection
Leukocyte trafficking
67
migration of leukocytes to sites of infection is _____ regulated
-highly
68
CAM:
cell adhesion molecules
69
what is the function of CAM
cells of a given tissue are held together by CAM
70
how are CAM important for immune cells
In order for cells of the immune system to participate in the inflammatory response, they need to use CAM to migrate to tissues where inflammation is taking place
71
Extravasation of leukocytes from _______ into ______ or entrance of leukocytes int ______ requires adhesion to the endothelium
Extravasation of leukocytes from blood vessels into inflamed tissues or entrance of leukocytes into lymph nodes requires adhesion to the endothelium
72
some of the _____ present on leukocytes are required for leukocyte-leukocyte interaction
CAM
73
how are CAM typically expressed
- Most are constitutively expressed
| - some are expressed dependent on local conditions
74
what are the 4 families of proteins that make up CAMs
- selectin
- Mucins
- Integrins
- Ig-superfamily CAM
75
what are selectins
-membrane glycoproteins containing extracellular lectin domains bind carb moieties found on mucin like molecules
76
what are the most important selectins
-Selectin-E,L,P
| (CD62E, CD62L, and CD62P respectively
77
where is selectin L expressed
on leukocytes
78
where are selectin P and E expressed
on the endothelium during inflammation
79
selectin P is contained in ______ found in ________ cells
- granules
| - endothelial
80
selectin P is released when:
the granules fuse with the cell membrane
81
Selectin E is synthesized ______ after stimulation by _____
- De novo
| - cytokines
82
what are selectins responsible for during the initial vascular phase of inflammation
-leukocyte interaction with the endothelium during the initial vascular phase of inflammation
83
What are mucins:
a group of heavily glycosylated, serine- and threonine-rich proteins that bind to selectins
84
what are some examples of Mucines
- CD34 or GlyCAM-1 on endothelial cells bind to CD62L on leukocytes
- PSGL-1 on neutrophils binds to selectin E and P on endothelial cells
85
what are integrins:
Heterodimeric proteins consisting of alpha and beta chains that are covalently joined at the cell surface
86
what do the alpha and beta chains of integrins form
-the alpha and beta chains of the integrins form a binding site to which the Ig superfamily domains bind
87
how are integrins divided into subgroups
integrins are divided into subgroups according to type of beta chain expressed (from beta 1 to beta 7)
88
Leukocytes express integrins with which beta chain
- beta2 chain
| - CD18
89
what does a deficiency in beta 2 integrin chains lead to
- immunodeficiency called leukocyte adhesion deficiency (LAD)- and autosomal recessive disease
- manifested by recurrent bacterial infections
90
what is the primary problem associated with LAD
- Leukocyte adhesion deficiency
| - neutrophils are unable to extravasate
91
CAM of the IG-superfamily contain
- Ig like domains
| - fibronectin domains
92
Important representatives of CAM Ig-superfamily are:
- ICAM-1 (CD154)
- ICAM-2 (CD102)
- ICAM-3 (CD50)
- VCAM (CD106)
93
Ig-superfamily CAMs bind to______
integrins
94
where are Ig-superfamily CAMs expressed
on endothelial cells
95
Endothelial cell activation:
- during inflammation, cytokines and other mediators of inflammation stimulate the endothelial cells leading to increased expression of CAMs
- leukocytes can now exit the blood vessels into the inflamed tissue
96
Extravasation of leukocytes is divided in to _____ phases
4 phases
97
what are the 4 phases of extravasation of leukocytes
1) rolling
2) activation
3) arrest/adhesion
4) transendothelial migration
98
Rolling:
at the site of injury, leukocytes, with the aid of their mucin CAMs, loosely bind to selectin E and P on the endothelial cells, their movement slows down and they begin to roll on the endothelium
99
Activation
- increase in cytokine, particularly chemokine secretion by endothelial cells
- Increase in chemokine receptor expression on leukocytes leading to activation of leukocytes
100
Adhesion (strict adhesion)
- Activation of the endothelium and leukocytes produces conformational changes in cells
- Integrtins oin leukocytes can now bind firmly to the endothelium
101
Diapedesis (transendothelial migration)
- leukocytes squeeze in between two neighboring endothelial cells and pass into the inflamed tissue
- Leukocytes use homotypic binding of platelet-endothel;ial cell adhesion molecule 1 (PECAM-1 (CD131)) on endothelium (self to self binding)
102
T/F neutrophils are among the last cells to arrive at the site of inflammation
F neutrophils are among the first cells to arrive at the site of inflammation
103
do neutrophils bind to endothelial cells under normal circumstances?
no neutrophils do not bind to endothelial cells under normal circumstances (i.e. without inflammation)
104
neutrophils can not migrate (extravasation) without inflamation because
- there is no expression of selectin E, P and other CAMs on the endothelium
- the expression has to be induced
105
which receptors are responsible for rolling of neutrphils
- selectin L
| - PSGL-1
106
which receptors are responsible for activation of neutrophils during extravasation
- IL-8
| - MIP-1beta
107
Activation also leads to increased expression of ICAM on the _________ and CD11a/CD18, CD11b/CD18(LFA-1 and MAC-1) on ________, leading to firm adhesion and finally diapedesis
- endothelium
| - Neutrophils
108
after diapedesis, the chemokine _____ then leads the neutrophils to the focal pont of inflammation
gradient
109
______ arrive slightly late at the site of inflammation, because high expression of _______ and ______ is possible only after the activation stage
- Monocytes
- VCAM-1
- ICAM-1
110
why might under normal circumstances might a monocyte extravasate
for the purpose of replenishing tissue macrophages and dendritic cells
111
what regulates the homeostatic migration of monocytes
CXCL14
112
what cell protein is responsible for monocyte cell rolling
CD63L
113
What protein is responsible for the regulation of activation of monocytes
MCP-1
114
what protein is responsible for diapedesis of monocytes
PECAM-1
115
Complement receptors such as ______ and ______, bacterial peptides participate in _______ of monocytes into inflamed tissue
- CR3
- CR4
- extravasation
116
where is the typical migration of lymphocytes under normal conditions
-Lymphocytes are continuously circulating between blood and lymphatic tissues
117
Extravasation of lymphocytes is similar to that of ________
neutrophils
118
where will lymphocytes migrate to
-lymphocytes will migrate toward areas of infection
119
lymphocytes use the same mechanism to extravasate into inflammatory sites or ____________
secondary lymphoid organs
120
where do lymphocytes pass through when they extravasate
- (HEV) high enothelial venules
| - they pass through post capillary venules called HEV
121
which receptors activate lymphocytes in HEV prior to extravasation
-Chemokines CCL19, CCL21, and CXCL12
122
Under optimal conditions will the inflammation response become a systemic response
No the inflammatory response should remain confined to a localized area under optimal conditions
123
in some cases of local injury what can cause the systemic manifestation of an systemic inflammatory response
--inflammatory mediators are released into the circulation
124
what is the most prominent systemic manifestation of inflammation
- the acute phase response
- Alterations in white blood cell count (leukocytosis or leukopenia)
- high fever
- sepsis and septic shock also called the systemic inflammatory response
125
APR
acute phase response
126
APR definition
changes in serum proteins during infection is referred to as APR
127
Proteins whose concentration increase or decrease during infection as referred to as
acute phase response protein (APP)
128
what are some important examples of APP
- some complement system proteins
| - C-reactive proteins (CRP) are part of the innate immune response
129
where are most APR proteins synthesized
in the liver
130
synthesis of APR proteins are induced by _____________ produced by phagocytes (TNFalpha, IL-1, IL-6)
-pro-inflammatory cytokines
131
CRP bound to the surface of microbe promotes uptake by phagocytes and activates ___________
-complement mediated attack
132
Mannose-binding lectin is a APP that recognizes mannose on ________ and not on _______
- microbes
| - veterbrate cells
133
what are other systemic effects of inflammation
- anorexia
- altered sleep patterns
- lethargy
- muscular wasting
- metabolic acidosis (lowered blood pH)
134
cachexia:
muscle wasting
135
what is the main characteristic of inflammation mediators in vivo that ends the inflammation response
-short half-life
