Robin Chapter 3 Flashcards

1
Q

What are NOD-like receptor (NLR)?

A

A cytosolic receptor that detect molecules that are liberated as a consequenence of cell dammage, which are:
uric acid, ATP, reduced K+, DNA etc. Activates inflammasome, which induces the producion of IL1

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2
Q

What are the 5 R of inflammatory response steps?

A

Repair, Regulation, REmovl of the agent, Recruitement, REcognition

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3
Q

How does histamine (and bradykinin, leucotrienes, etc) cause vascular permeability of postcpillary veinules?

A

Contraction of endothelial cells. It is short-lived (15-30 min) except in some forms or mild injury like burns, UV, toxins where leakage begins after 2-12 hours and last for hours of days (endothelial injury)

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4
Q

What is the role of those proteins in migration of leucocytes through the capillaries?
- selectin
- chemokins (usually bound to proteoglycans)
- integrins
- CD31

A
  • selectin: rolling
  • chemokins/proteoglycans: acivating neutrophils to increase avidity of integrins
  • integrin: firm adhesion
  • CD31 (PECAM-1): transmigration
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5
Q

P-selectin is expressed on…. (2)

A

endohelium and platelet

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6
Q

Chemotactic agents (cytokines, complement (C5a), archidonic acid metabolites like LTB4) bind to which receptor on the leucocyte?

A

seven-transmembrane G protein-coupled receptors

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7
Q

Release of leucocytes from the bone marrow is caused by cytokines that include ___ and ___

A

TNF and IL-1.

These are released in huge number during sepsis

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8
Q

which comes first: vasodilatation or permeability?

A

Vasodilatation, then permeability (think becomes red b4 swelling). Both caused by histamine. increased permeability also caused by other kinins

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9
Q

Give their roles in leucocytes recruitment:

Selectins:
Chemokins:
integrins:
CD31 (PECAM-1):
ICAM-1:
IL-1:
TNF:
VCAM-1

A

selectins: rolling
chemokins: acivating neutrophils to increase avidity of integrins
Integrins: firm adhesion
PECAM-1: transmigration
ICAM-1 (binds to LFA-1): integrin ligand (on the endothelium)
IL-1 and TNF : activate endothelium (increase adhesion molecules), and promote the release of cytokines for chemotactic gradient
VCAM-1 (binds to VLA-4): intergrin ligand on endothelium

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10
Q

P selectin is expressed on:

A

platelet AND endothelium

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11
Q

Which is the most common exogenous factor causing chemotaxis? (Starts with N)

A

peptides with N-formylmethionine terminal (bacterial product)

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12
Q

Name the 3 phagocytic receptors

A

mannose receptor, scavenger receptor (binds the LDL) and opsonin receptor (C3b, plasma lectins, IgG)

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13
Q

On top of being involved in microbial killing, NO does soemthing else:

A

vasodilatation

eNOS: endothelial
nNOS: neutronal
iNOS: inducible (involved in microbial killing

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14
Q

difference between acid protease and neutral protease (granules in neutrophiles

A

acid protease: degrades bacteria and debris with phagolysosomes

neutral protease: destruction of extracellular components -> tissue desctruction that accompany inflammation

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15
Q

Two types of granules in neutrophils: what are their main difference?

A

specific (secondary granules), constituted of ex: collagenase and primary azurophil granules

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16
Q

what are alpha1 antitrypsin and alpha2-macroglobulin

A

antiproteases

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17
Q

What are NET

A

extracellular fibrillar network that concentate antimicrobial substances at site of infection and trap microbes, preventing their spread. It is composed of nuclear chromatin

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18
Q

lipoxins are pro or antiinflammatory

A

anti

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19
Q

MEdiators are either secreted by _____ or generated from _____

A

cells (sequestered in cells, rapidly secreted), plasma proteins (liver, exemple complement)

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20
Q

2 major vasoactive amines:

A

histamine, serotonin

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21
Q

Histamine is secreted secondary to binding of IgE antibodies OR (2 answers)

A
  1. cold, heat, physical injury
  2. anaphylatoxins, which are products of complement, C3a and C5a
  3. Neuropeptides like P substance and IL1 and IL8 can also trigger release of histamine
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22
Q

Serotonin is a preformed vasoactive mediator present in which cells? (2)

A

platelets and neuroendrocrine cells

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23
Q

TxA2 2 roles (thromboxane A2)

A

vasoconstriction and platelet agreggating

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24
Q

Prostacyclin role (PGI2)

A

vasodilation and inhibition of platelet agreggation (so contrary of thromboxane)

+ increase of vascular permeability and chemotactic effect of other mediators

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25
this molecule of the aracidonic acid metabolites is involved in pain
prostaglndin (PGE2) Also involved in fever
26
Which is more potent for causing bronchospasm and increasing vascular permeability: leucotriene or histamine?
leucotriene (C4, D4 E4)h
27
which two cell population are required for synhesis of lipoxins?
neutrophils and platelets
28
Name 3 cytokins that cause fever AND leucocyes production in the bone marrow
IL1, IL6, TNF
29
Name 2 cytokins that cause that increase acture phase proteins
IL1, IL6
30
What does IL8 does
chemotaxis and activation of neutrophils
31
chemokines binds o which receptor type?
G protein coupled receptor
32
chemokines are important in acute inflammation AND
maintenance of tissue architecture (ex: spleen and lymph node)
33
complement: innate, adaptive or both?
both
34
which is the critical step in the complement activation? and which are the 3 pathways?
cleavage of C3 pathway 1: classic (antibodies) pathway 2:Alternative (endotoxin, LPS, venom, etc) pathway 3: lectin pathway (mannose binding lectin binds to carbs on microbes)
35
Name the 3 complement proteins that are anaphylatoxins
C3a, C5a, (C4a)
36
Which complement protein activates the lipoxyfgenase pathway of AA metabolism?
C5a. It is also a chemotaxis agent for many leucocytes
37
what can platelet activating factor do on top of platelet aggregation?
vasoconstriction, bronchoconstriction. At low concentration: vasodilataiton and increased vascular permeability
38
Bradykinin has effects similar to which chemical?
Histamine. Bradykinin also cause pain. action is short lived
39
Substance P role in inflammation (2)
pain and vascular permeability
40
3 sites of production of macrophages
bone marrow in pos natal life-> blood monocyte and skin and intestine macrophages yolk sac and liver-> resident macrophages
41
2 major pathways of macrophage activation, and what they are:
classical and alternative classical:main role is to destroy microbes and promote the inflammatory response. Alternative: terminate inflammation and promote tissue repair. induced by cytokines other than IFN gamma, such as iL4, IL13
42
pathogenesis of fever
exogenous pyrogens ex LPS-> stimulate lymphocytes to release IL1 and TNF (acute phase response, as well as IL6) -> induce production of prostaglandin (PGE2) in hypothalamus
43
Name the 3 most important acute phase protein (synthesised in liver)
SAA (serum amyloid A), fibfinogen, C reactive protein (CRP)
44
which cell is the most important source of growth factor when a tissue is injured?
macrophages
45
proliferation of hepatocytes following partial hepatectomy steps
1. TNF simulates Kupffer cells to release IL6 2. HGF and TGF, produced by many cells type, acted on primed hepatocytes (by IL6) to stimulate cell metabolism and make them enter the cell cycle 3. replication of nonprenchymal cells 4. return to quiescence
46
When does liver regenerate from progenitor cells?
chronic liver injury and inflammation (proliferative cpacity impared). Some of the progenitor cells are in canal of Herring
47
What is the name of the pathway that regulates the sprouting and branching of new vessels?
Notch pathway. VEGF stimulates the expression of notch ligands which binds to the notch receptor on endothelial cell
48
ECM proteins prticipate inn the process of vessel sprouting in angiogenesis largely through interactions with ___________ receptors in endothelial cells
integrins
49
Which is the most important cytokin for the synthesis and deposition of connective tissue proteins
TGF-beta. PRoduced by most cells in granulation tissue
50
TGF beta increase or decrease metalloproteases
decrease (inhibit), which decrease DEGRADATION of ECM
51
What are TIMPs?
tissue inhibitors of metalloproteinase
52
cellular receptors for microbes are in the cytosol, plasma membrane and ________
endosomes
53
Give 3 things NOD like receptors can detect
uric acid, ATP released from damaged mitochondria reduced K+ concentration DNA hanging around in the cytosol
54
What does NOD like receptors activate
an inflammasome, which produces IL-1, which recrutes leucocytes
55
vasodilatation starts with arterioles or capillaries?
arterioles
56
Which leucocyte produces growth factor that aid in repair of tissues?
macrophages
57
Histamin does vasodilatation, increased permeability or both?
both
58
Which cytokines (2) act on endothelial cells of post capillary veinules to express adhesion molecules and endothelial ligand like VCAM-1 and ICAM-1?
TNF and IL1
59
In which kind of blood vessels does transmigration occurs?
postcapillary veinules
60
does actin gets polymerized at the leading edge of cells or at the back?
Leading edge. Myosin filaments are at the back
61
Which leucocyte attaches better to the adhesion molecules of endothelium?
neutrophils
62
Activated leucocytes have more ____ (element) in their cytosol
calcium
63
Name 3 antioxydants other than glutathione peroxydase and superoxyde dysmutase
catalase, ceruloplasmine, iron free fraction of plasma transferrin
64
What is the name of the primary neutrophil grnaules? what are the secondary granules for?
primary granules: azurophils secondary granules: they are more specific
65
Difference between acid protease and neutral protease in what they do
acid protease degrade bacteria and debris in the phagolysosome neutral protease degrade extracellular components (collagen, fibrin...) resulting in tissue destruction
66
What do NET do?
They are neutrophil extracellular traps, they are fibrillar networks that concentrate antibicrobial substances at the sites of infection and traps microbes, helping to prevent their spread
67
Movement of cells/phagocytosis: myosin filaments is in the back or front? Polymerisation of actin?
Myosin: back Polymerisation: back
68
Which one produces more cytokines, neutros or macrophages? And secretion of lysosomal enzymes?
Macrophages, neutrophils
69
Which receptor doesnt have as a functional outcome to kill microbes: G protein coupled receptor, toll like receptor, phagocytic receptor
G protein coupled receptor
70
Platelet activating factor (PAF) commes from which cells ?
Leucocytes, mast cells
71
Leukotrienes vasodilate or vasoconstrict?
Vasoconstricts
72
In the Arachidonic acid metabolites, which 2 do chemotaxis?
5-HETE and leucotriene B4 (and PGD2 for neutrophils)
73
Which cytokines activate classically activated macrophages (M1) vs alternatively activated macrophages (M2)?
IFN gamma= M1, IL13, IL4 = M2 To note that microbial products also activates M1
74
what is a tertiary lymphoid organ?
lymphoid organogenesis seen in chronic inflammation (formation of lymphoid follicule)
75
What does PCSK9 do? (hint: cholesterol metabolism)
Inhibits recyling of LDL receptorsn (reduces the amount of LDL receptors, therefore increase levels of blood cholesterol
76
How does a secondary storage problem differs from primary storage problem in lysosomal disease?
secondary storage: happens when there is no autophagy of mitochondria -> accumulation of aberrant mitochondria -> free radicals -> intrinsic apoptosis triggered
77