Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Infection & Immunity > Inflammation > Flashcards

Inflammation Flashcards

(102 cards)

Start Studying
1
Q

what does inflammation involve

A

interplay between leukocytes (WBCs), tissue cells (immune, structural), microvasculature, nerves, chemical mediators of inflammation
plasma derived

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what are the cardinal signs of inflammation

A

heat, redness, swelling, pain, loss of function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what causes heat and redness

A

arteriolar dilation, increased blood flow to inflamed tissue

increased blood flow due to relaxation of artieries

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what causes swelling

A

leakage of plasma from blood vessels into tissue (plasma extravasation)
more chronic swelling due to tissue remodelling, cellular accumulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what causes pain

A

external physical or chemical injury; endogenous generation of chemical mediators of inflammation trigger sensory nerves

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what causes loss of function

A

due to chronic inflammation dur to tissue remodelling (tissue destruction/fibrin disposition-scarring)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what are the cellular components of the inflammatory response

A

leukocytes (WBCs)

granulocytes (neutrophils, eosinophils, basophils), lymphocytes (T,B,NK cells), monocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what are tissue mast cells

A

widely distributed throughout connective tissue and mucosal surfaces, similarities with circulating basophils, contain synthesise and release inflammaotry mediators

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what are stimuli of tissue mast cells

A

mechanical injury to skin, hypersensitivity, chemicals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what is the role of the endothelium in inflammatory response

A

blood vessels lined in epithelium
endothelial-derived NO causes arteriolar dilation; endothelial contraction makes venules leaky due to increased permeability
causes oedema

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what are chemical mediators of inflammation

A

diverse molecules produced by the host in response to infection and immune reactions
low specificity (not antibodies)
effectors of the innate immune response but modulate the specific response
promote inflammation and hopefully initiate repair

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what is the triple response of histamine

A

redness due to vasodilation, flare (neuropeptide release causing itching), wheal (swelling)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what is the action of histamine on blood vessels

A

relaxation of arteriolar smooth muscle

contraction of venular endothelium leading to increased permeability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what category of drug is chlorphenamine

A

H1 receptor antagonist

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what are some chemical mediators in inflammation

A

PGE2 and PGI2 cause vasodilation

histamine and bradykinin increase venule permeability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what is bradykinin

A

inflammatory substance formed from plasma precursor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what is PGE2 (prostaglandin)

A

inflammatory substance formed from membrane lipid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what pre-formed mediators are released in response to local injury

A

histamine, mediators from membrane lipids (PGE2, PGI2), release of peptides from neurokinins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what mediators are produced during inflammatory response

A

following proteinase activation, bradykinin and complementing fragments are formed, as well as products of infiltrating cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what mediators take hours to produce after inflammatory response

A

transcription and translation of proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

why is inflammation beneficial

A

increased supply of cells and chemical mediators to site of inflammation (redness, swelling, removal of damaged tissue or infectious agents)
tells body to rest to relieve pain and loss of function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what are eicosanoids

A 
oxidation products of 20-carbon fatty acids (arachidonic acid)
classical eicosanoids (prostaglandins), non-classical eicosanoids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what is the process of prostaglandin biosynthesis

A

membrane phospholipids react with phospholipase A to form arachidonic acid which reacts with cyclo-oxygenase to form PGH2
then forms tissue specific isomerases
synthesis is low under basal conditions
profile and rate dramatically altered in inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what are prostaglandin receptors

A

prostaglandins act via specific GPCRs on target cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
what are some examples of prostaglandin receptors
PGE2 receptors, prostacyclin, thromboxane, PGD2 receptors
26
what are the hysiological functions of PGs
initiation of labour, inhibition of gastric acid secretion/increased gastric mucous production, inhibition of platelet aggregation and vasodilation, platelet vasodilation and aggregation
27
what is EP2
pro-inflammatory receptor Gs/AC mediated elevation of cAMP in smooth muscle vasodilates can inhibit leukocyte function and have anti-inflammatory properties
28
what is the Von Frey pain perception test
prostaglandin receptors are on sensory nerves; EP1 receptors knock-out mice have decreased pain perception it increases pain signals to the brain
29
what does an EP3 receptor do
activates leukocytes and mast cells (Gi linked receptor reduces AC/cAMP signalling; enhances function) enhances oedema formation
30
how to prostaglandins act in fever
protective against infection, dangerous if prolonged or severe, regulated by production of PGE2 in the hypothalamus
31
what is cyclo-oxygenase
``` exists in two isoforms COX1 constitutive (products important in normal function of stomach, intestine, kidney and platelets) COX2 induced (especially during inflammation) COX3 splice variant of COX1 expressed in CNA ```
32
what is the target of aspirin
cyclooxygenase (enzyme that converts arachidonic acid into prostaglandin)
33
what binding effects does aspirin have
covalent binding, acetylates COX, irriversible inhibition of COX, releases salicylate
34
what binding effects does ibuprofen have
competitive inhibitor of arachidonate binding to COX | non-selective COX inhibitor
35
what are the side effects of aspirin like drugs
gastric irritation, bleeding, renal toxicity, bleeding due to COX1 inhibition and reducing cytoprotective effects of PGs
36
what are the anti-thrombotic actions of aspirin
irriversibly acetylates cyclo-oxygenase, thus platelet TXA2 production ceases; endothelial cells make new COX and so PGI2 is still released
37
what happens when aspirin is used for anti-thrombotic effect
COX inactivated by low dose aspirin platelet COX1 inactivated for the life of the platelet; blood vessel COX rapidly resynthesised PGI levels maintained and decreased thrombus formation
38
what is the action of leukotrienes
bronchoconstriction, oedema, chemotaxis, present in inflammation
39
what is the action of leukotrienes on bronchoconstriction
LTC4 and LTD4 constrict human bronchial smooth muscle which increases effects of other constrictor agents
40
what is the action of leukotrienes on oedema
LTC4 and LTD4 stimulate increased vascular permeability | LTB4 increases vascular permeability (neutrophil dependent)
41
what is the action of leukotrienes on chemotaxis
LTB4 potent chemotactic agent for inflammatory cells | BLT1 receptor
42
what is the action of leukotrienes in inflammation
high levels in synovial fluid of RA pts
43
how do glutocorticoids work
inhibit PLA2 so arachidonic acid is not produced
44
how does zileuton work
inhibits 5-lipoxygenase activity
45
how does montelukast work
inhibits leukotrienes
46
what action do glutocortecoids have on eicosanoids
inhibits PLA2 transcription, induces synthesis of endogenous PLA2 inhibitor 'lipocortin'; inhibits COX2 synthesis
47
why are eicosanoids important
potent vasodilators, increase vascular permeability, pain, fever, synergy with other medications, modulators of cell function
48
what is leukocyte migration
leukocytes move from blood to sites of inflammation and immune activation directional control is co-ordinated by tissue expression of adhesion molecules and chemical stimuli for leukocyte migration on arrival at sites of inflammation, they precipitate in host defense, inflammation and repair/restoration
49
what is leukocyte diapedesis
1. circulation 2. tethering/rolling 3. firm adhesion 4. transmigration
50
what happens in the tethering/rolling stage of leukocyte dispedesis
fast moving leukocytes tethered to blood vessel wall, guided by specific homing receptors and their ligands called selectins (binds carbohydrate structures with weak bonds) most important stage is initial tethering of leukocytes to vascular cells
51
what are selectins
lectin-like adhesion molecules that weakly bind CHO molecules
52
where are L-selectins found
leukocytes
53
where are P-selectins found
platelets and endothelium
54
where are E-selectins found
endothelium
55
what is L-selectin
constitutive expression on leukocytes leukocyte activation leads to transient increase in avidity (molecules cluster on surface) rapid shedding by proteolytic cleavage
56
what is P-selectin
constituative in platelets and endothelium, stored in granules rapidly translocated to cell surface on cell activation by thrombin or histamine
57
what is E-selectin
endothelial expression induced by cytokines or LPS expression required de novo protein synthesis (slow) expression inhibited by glutocortecoids
58
what is leukocyte adhesion deficiency II
patents suffer recurrent infections (no pus, neutrophilia) normal phagocytosis and respiratory burst in vitro defective fucose metabolism (leukocytes do not express selectin ligands) decreased rolling response on E- or P-selectins severely impaired neutrophil accumulation in skin inflammation neutrophils stuck in vascular area (causes neutrophilia) neutrophils do not escape circulatory system
59
what happens in the firm adhesion and flattening stage of leukocyte dispedesis
rolling along endothelial cell surface which activates integrins subsequent to receiving signals from chemokines on the endothelial surfaces
60
what are integrins
firm adhesion occurs via integrins | heterodimeric proteins expressed on the surface of leukocytes and most other cells
61
how is adhesion regulated
basal expression of integrins, leukocyte activation induces conformational change which increases affinity and clustering of integrins
62
what is leukocyte adhesion deficiency I
patients suffer recurrant bacterial infection without pus leukocytes do not adhere to extracellular material or endothelium in vitro LAD I leukocytes are deficient in beta2 integrin
63
what are integrin ligands
intracellular adhesion molecule (ICAM) ICAM2 basally expressed on endothelium ICAM1 induced by cytokines
64
what is transmigration
involves CAMs and chemoattractants (chemotaxins)
65
what are examples of leukocyte adhesion blockers in therapy
anti VLA-4 | anti alphaL beta2 in dry eye symdrome
66
what is natalizumab
monoclonal antibody against alpha4 integrin, inhibits T lymphocyte interactions with brain endothelium (decreased trafficking into the brain); trialled as therapy for MS licenced in US for IBD
67
what is chemotaxis
leukocyte movement
68
what stimulates leukocyte movement (chemotaxis)
chemotaxins | they attract leukocytes - intigrin affinity and avidity change, movement
69
what is the source of chemotaxis
site of inflammaion some are immobilised and 'presented' to leukocytes; endothelial cell surface presentation, bound onto extracellular matrix
70
what are some non-selective chemotaxins
LTB4, C3a, C5a, formyl peptides
71
what are some selective chemotaxins
chemokines (large family of proteins)
72
what are chemokines
structurally defined group of chemotaxins that are produced in response to IL-1, TNF and bacteria G-protein coupled receptors named according to ligand (-L) and receptor (-R)
73
what are CXC chemokines
mainly neutrophil and T cell attachments target CXCL8 ligand and CXCL12 ligand their targets are neutrophils, lymphocytes and stem cells
74
what are CC chemokines
not neutrophil attractants | ligands targeted are CCL2, CCL11 and targets are monocytes, eosinophil, activated T-cells
75
what rate does each WBC move at
neutrophils>monocytes>lymphocytes neutrophil-acute inflammation monocytes, lymphocytes - chronic inflammation
76
what is the tissue response in inflammation
different selectin and CAM expression, different chemokine expression
77
what is the leukocyte response to inflammation
different integrin expression, different chemokine receptor expression
78
where are integrins active
on CAM during adhesion part of leukocyte dispedesis
79
what happens during leukocyte transmigration
leukocytes escape from circulation and accumulate at sites of injury selectins tether leukocytes on endothelium near inflammatory site integrins are used for stronger adhesion on chemokine activation of leukocytes CAMs expressed by endothelium are ligands for integrins leukocyte movement directed by chemotaxis
80
what are proteases derived from
plasma zymogens, tissue cells, activated leukocytes
81
what do proteases have a central role in
host defense, removal of damaged tissue, initiating repair, inflammation
82
what are plasma proteins
interrelated systems activated by tissue injury, antibody complexes, foreign surfaces generate inflammatory mediators from plasma precursors kinins (vasodilation, increased permeability, pain) complement (leukocyte activation, chemotaxis, mast cell degranulation, bacterial opsonisation and lysis) clotting cascade (thrombosis, platelet activation)
83
what is angioedema
deep cutaneous and mucosal swelling; lasts days and most pts also suffer mast cell degranulation, responsive to H1 antagonists histamine-independent forms may be drug induced (like ACE inhibitors) or hereditory
84
what proteases are involved in angioedema
``` angiotensin converting enzyme inhibitor (blocks bradykinin degredation so increases inflammation) hereditary angioedema (increases bradykinin, decreases protease inhibitors) trated with bradykinin receptor antagonist ```
85
what are the families of proteolytic enzymes
matrix metalloproteinases, serine proteinases, cysteine proteinases
86
what tissue damage occurs in RA
``` cartilage proteoglycans (matrix material) lost rapidly in RA so shock absorption impaired and loss of function proteoglycans have an open structre and are highly accessible and sensitive to breakdown by several proteinases collagen is lost more slowly which causes loss of function of cartilage as smooth surface ```
87
what are matrix metalloproteinases
``` break down collagen and other matrix proteins active at neutral pH, contains and requires Zn2+ major class of enzymes that degrade cartilage inhibited by endogenous TIMPS (tissue inhibitors of metallo-proteinases) ```
88
what activates metalloproteinases
removal of propeptide by other proteases chemical modification of propeptide by RONS active zinc site targeted by hydroxamate series of MMP inhibitors
89
what is the cysteine switch mechanism
propeptide maintains MMP in an inactive state; interaction between conserved cysteine residue in pro-domain and active site zinc ion is disrupted; active site becomes accessible and MMP is activated; pro-domain does not need to be removed of a proMMP to acquire activity; only disruption of the zinc-thiol interaction is absolutely required
90
what are peptidomimetics
synthetic MMP inhibitors used in inflammation
91
how do peptidomimetics work
small hydroxamic acid based molecules used in zinc binding, based on collagen structre, inhibit MMP ativity they lack specificity and act on most metalloenzymes
92
how do non-peptide hydroxamates compare to peptidomimetica
they have better selectivity
93
what are other inhibitors of MMPs
tetracycline derivatives, antibody therapies, endogenous inhibitors (TIMPs)
94
what are some examples of serine and cysteins proteinases
neutrophil elastase - acive at neutral pH, breaks down matrix proteins like chondritin and proteoglycans endogenous inhibition by serpins (serine protease inhibitors) serpins are readily inactivated by oxidation
95
what are some adverse effects of MMP inhibitors
muscoskeletal inhibitors, lack of specificity, key role in homeostatic connective tissue turnover
96
what does RONS stand for
reactive oxygen and nitrogen species
97
what is the role of RONS
essential for host defence
98
how are RONS produced
infiltrating leukocytes and tissue resident cells NADPH catalyses formation of O2- which forms H2O2 which is further metabolised to HClO (H+ and ClO-) H2O2 inactivated by catalase reactive nitrogen species formed from NOS derived NO- combining with oxygen species
99
what is respiratory burst
leukocytes phagocytose bacteria, yeast, immune complexes, damaged tissue proteases and ROS generated as part of host defence
100
how do ROS' cause joint damage
rheumatoid synovial tissue undergoes cycles of hypoxia and reperfusion (oxidative stress); immune complex formation in some diseases, generation of superoxide and RONS (tissue injury, modulation of cell function)
101
what are the effects of RONS
activation of inflammatory gene transcription; amino acid modifications; matrix modifications; DNA damage; cell apoptosis and necrosis
102
what are some resident RONS for inflammation
chondrocytes, osteoclasts, fibroblasts

Infection & Immunity (22 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions