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Recap 3 Flashcards

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1
Q

LPS binding receptors

A

TLR4 = NLR inflammasome and produce ILB
CD14 = activate endocytosis

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2
Q

What are some secreted PRR

A

Collagenous lectin = mannan-binding lectins A et C
Ficolins
Surfactant proteins A (SP-A) et D
Conglutin (cattle)

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3
Q

What can NFkB and p38 induce (exception)?

A

Phagocytosis, DC activation, release inflamm cytokines, active innate immune system
TLR4 signaling = doesn’t engage MyD88 = form IFNy
TLR3 et 4 independent of MyD88

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4
Q

Through what do TLR and C-type lectin regulate innate and adaptive responses?

A

NFkB, TFAP-1, IRF

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5
Q

Mechanisms of NLR

A

Binding of NLR -> activate RIPK2 -> induce NFkB (facteur de transcription) = secretion of antimicrobial peptides, inflamm mediators, MAPK active for gene transcription and regulation of autophagy

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6
Q

Composition of NALP3 inflammasome
Release of

A

Multimeric protein units consits of NLR sensing molecule, ASC adaptor protein, caspase 1
Release of IL1B, IL18, IL33

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7
Q

What are alarmins?

A

Sulfate, hyaluronan, heat schock protein (HSP60), Gp96 (endoplasmic reticulum), fibronectin, fibrinogen, SP-A
Generate inflammation against neoplastic cells, toxins, mechanical injury
Can induce NLRP3

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8
Q

TNF and IL1 induce endothelial expression of integrin ligand :
1. VCAM-1
2. ICAM-1
3. PECAM-1
4. JAM A-B-C

A
  1. VCAM-1 - ligand for B1 integrin VLA4
  2. ICAM = LFA-1, MAC-1
  3. PECAM = on endothelial cell membrane
  4. JAM = mediate adherence activity
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9
Q

Where does leucocytes migration happen?

A

Mainly in postcapillary venules

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10
Q

Organisation of filopodia of leucocytes for migration

A

Polymerization of actin at the leading edge (VLA3 binds fibronectin) and localization of myosine at the back (tail anchored by LFA1)

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11
Q

Molecules causing mast cells degranulation

A

Fce-R to IgE
Substance P (released from C-reactive nerve fibers)

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12
Q

Granules of eosinophils

A

Small = arylsulphatase, acid phosphatase, MMP, gelatinase
Primary
Large Sp secondary = Major basic protein (MBP = inhibe heparin), cationic protein, eosinophil-derived neurotoxin, eosinophil peroxydase, histamine, lysosomal enzyme

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13
Q

Eosinophils produce which cytokine

A

IL1 à 6, 8-10-12-16, GM-CSF, TGFa et B, chemokines

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14
Q

Chemoattractants of eosinophils

A

Histamine
Eosinophil chemotactic factor A (from mast cells)
C5a
IL4-5-13
Chemokines (CCL5/RANTES, CCL11/eotaxin)

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15
Q

NK cells (sentinel) receptors and products

A

CD161 not CD3
Type I = 95% express CD56 produce IFNy
Type II = lack CD56 produce IL4, IL5, IL13 (Th2 response)

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16
Q

Regulation of active and inactive NK (sentinel)

A

IL21 regulates differenciation
Inactive stimulated by Flt-3 ligand, IL4, IL12, IL15, IL21
Activated leads to upregulation of CD16 and IFNy

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17
Q

R for NK-LT

A

CD3+
Recognize CD1d = induce release of IFNy, IL4, GM-CSF

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18
Q

Subtypes of IgG y Fc-R

A

ITAM domain = macro activation
ITIM domain = inhibe activation

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19
Q

How are ROS produced ? Damage cell?

A

Rapid assembly and activation of a multicomponent oxidase called NADPH oxidase = réduit NADPH en O2-
Damage through lipids peroxydation, cross-link of proteins, oxide thiol groups on methionine and cysteine, cleave glycoconjugates, directly damage DNA

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20
Q

Microbicide action of neutrophils

A

Azurophilic granules contain MPO = converts H2O2 to HOCl (hypochlorite = bleach)
Destroy microbes by halogenation or peroxidation

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21
Q

Antioxidant
1. Enzymatic
2. Non enzymatic endogene
3. Non enzymatic dietary

A
  1. SOD, catalase, thioredoxin, peroxiredoxin, glutathione peroxidase
  2. Ceruloplasmin, transferrin, metallothionein, uric acid, melatonin
  3. VitA, C, E, lycopenes, flavonoids, resveratol, genistein, anthocyanin, naringenin, reserpines
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22
Q

Action of NO

A

VasoD, inhibe platelets aggregat, inhibe mast cell induced inflammation, oxidizes lipids, regulates chemotaxis
In macrophages interacts with superoxide to generate ONOO-

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23
Q

What do neutral proteases of neutrophils do?

A

Cleave C3 and C5 complement and release kinin-like peptide from kininogen

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24
Q

What do macrophages contain?q

A

Acid hydrolase, collagenase, elastase, phospholipase, plasminogen activator

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25
What does lyzozyme do?
Hydrolyzes the muramic acid-N-acetylglucosamine bond found in the glycopeptide coat of all bacteria
26
Action of defensin, cathelicidin
Forms pores in microbial membrane Affects chemotaxis and activation of adaptive response
27
Action of elastase, inhibition
Hydrolyzes bacterial cell wall and tissue elastin A1-antitrypsin = major inhibitor of neutrophil elastas e
28
What does the release of deoxyadenosine by Staph aureus do?
Enzymes that degrade NET
29
Mechanism of NET formation
ROS dependent activation of arginine deaminase that converts arginine to citrulline leading to chromatin decondensation MPO and elastase enter nucleus = further decondensation
30
Role of IL17 + deficiency
Neutrophils recruitment If absent = susceptible to fungal/bacterial and develop cold abcesses
31
Functions of HIF-1a
Promotes phagocytosis Inhibe apoptosis Release antimicrobial peptide Granule protease VEGF Cytokine release Inducible NO synthese (iNOS)
32
Opsonin-R on neutrophils membrane
Complement (CR1, CR3) and Fc-R (binds C3b, C3bi) -> active GTPase Rac1 and B2 integrin MAC1 -> induce kinase + mediate actin assembly = formation of filopodia -> phagocytosis
33
Fusion in phagocytosis mediated by
Calmodulin and SNARE
34
Effects of neural impulses in termination of acute inflammation
Neural impulses (cholinergic discharge) inhibit production of TNF in macrophages
35
Role of 1. PGE2 2. PGD2 3. PGF2 4. PGI2 5. TxA2 6. LTB4 7. LTC4-D4-E4
1. PGE2 = fever 2. PGD2 = vasoD, chemoattractant for neutrophils 3. PGF2 = vasoC, smooth muscle contraction 4. PGI2 = vasoD, inhibe platelet aggregation 5. TxA2 = vasoC, platelet aggregation 6. LTB4 = chemotactic, permeability, ROS, release lysosomal enzyme 7. LTC4-D4-E4 = vasoC, bronchospams, permeability Leukotriene more potent than histamine in vascular permeability
36
Th1 CD4 lymphocytes : 1. Induit par 2. Express 3. Produce 4. Role
1. Driven by IL12 2. Express T-bet 3. Release IFNy 4. Cell-mediated immune response
37
Th2 CD4 lympho 1. Induit par 2. Express 3. Produce 4. Role
1. Forms in response of IL4, IL6, TSLP 2. Express GATA-3 3. Produce IL4-5-10-13 4. Induce humoral response (asthma, atopy)
38
Th17 CD4 lymphocytes 1. Induit par 2. Express 3. Produce 4. Role
1. Forms in response to TGFB, IL6, IL23 2. Express Roryt 3. Release IL17 4. Bridge innate and adaptive response
39
Treg prod et role
Develop in thymus and in response to antigenic stimulation in the presence od TGFB Modulate adaptive response to release of IL10
40
Follicular CD4 LT (TFH) role prod
Develop in presence of IL6 et IL21 Release IL21 = support LB development and AC production
41
TNF and IL1 production and functions
Produced by activated macro and DC TNF (LT and mast cells) IL1 (some epithelial cells) Functions in endothelial activation, activation of leucocytes
42
Action : SOCS PTP (SHP-2) PIAS
SOCS = inhibit JAK PTP = JAK and STAT PIAS = inhibe phospho STAT in nucleus
43
Functions of interferon
Inhibe viral replication, active NK cells and macro, increase AG-presentation to LT, increase resistance of host cells to viral infection
44
Mechanism of antiviral activity of IFNy type I
Based on expression of activation of ISGylation pathway, MxA protein, OAS1, RNase I, PKR
45
type 2 IFN (IFNy) action
Bind IFNy-R and signal through JAK and STAT to induce Th1 and Th17 response
46
Type 3 interferon produced by + mechanisms
Produced by intestinal and respiratory epithelial cells in response to viral infection Release of viral RNA in infected cells = active RIG1 = mediate MAVS on mitochrondria = active p38, NFkB and IRE3 = produce type 3 IFN
47
HMGB-1 role
Released by monocytes and macrophages Nuclear protein binds DNA to regulate gene expression Released by nearly all cells during necrosis = release alarmin Binds macrophage-R for products of RAGE and TLR2 and 4 -> release of TNFa and IFNy Involved in hypothalamic fct, food aversion, hypophagia, anorexia, weight loss, sickness behavior
48
Chemokines (cytokines)
Only cytokines that bind to GPCR
49
CXC chemokines Production Inducer
IL8 secreted by active macrophages, endo cells = activation and chemotaxis of neutrophils Induced by microbes IL1, TNF
50
C-C chemokines Receptor Production Action
CCR receptor Monocyte chemoattractant protein (MCP1, CCL2) Eotaxin CCL11 = recruits eosinophils Macrophages inflammatory protein MIP1a, CCL3
51
C chemokine lymphotoxin
Binds CR receptor Lymphotactin XCL1 = relatively specific for lymphocytes
52
CX3C 2 forms
- Cell surface bound protein = induced on endothelila cells = strong adhesion of monocytes and LT - Soluble form derived from proteolysis = chemoattractant
53
Chemokines receptors expressed on neutrophils
CXCR1 CXCR2 (binds IL8)
54
Monocytes chemokines ligands
CCL2-7-8-13
55
What is chemerin
Chemoattractant for DC and macrophages activated by cleavage and binds CMKLR1
56
Acute phase proteins
C-reactive protein = acid glycoprotein, haptoglobin, mannose0binding protein, firbinogen, a-antitrypsin, C3, C4, albumin
57
Action of : 1. Adiponectin 2. Lipoxin 3. Resolvin 4. Maresin 5. Annexin A1 6. Hydrogen sulfide
1. Adiponectin = anti inflamm, insulin sensitization, antiapoptotic 2. Lipoxin = active macro, alter neutro migration 3. Resolvin = inhibe neutro transmigration 4. Maresin = wound repair, reduce nerve sensitivity 5. Annexin A1 = released from dead neutro, inhibe further neutro infiltration 6. Hydrogen sulfide = apoptosis of neutrophils
58
Action of 1. C3a 2. C5a 3. C3b, C3bi 4. MAC
1. C3a = vascular permeability by histamine release from masto 2. C5a = anaphylotoxin, chemoattractant, expression of adhesion molecules, activates lipoxygenase pathway 3. C3b, C3bi = opsonin through CR1 and CR3 4. MAC = results from cleavage of C5 to form C5a et C5b C5b = anchor for C6, C7, C8 = polymerize C9 into a tube inserted in lipid bilayer = channel for ions = water osmosis = lysis
59
What does an inherited deficiency in C1 inhibitors do?
Angioedema
60
Functions of PAF
Platelet aggregation VasoC Leucocytes adhesion Bronchoconstriction
61
Complement involved in disposal of waste
C1q, C3, C4 fragments = clearance of immune complex and apoptotic cells
62
Functions of bradykinin
Permeability Contraction of smooth muscle VasoD Pain Stimule phospholipase A2 (AA metabolism) Hypotension Bronchoconstriction
63
M1 (classic) and M2 (alternatif) macrophages induced and action
M1 : induced by microbial, IFNy, TNF = role in destruction of microbes and inflammation M2 : induced by IL4, IL13 = role in tissue repair and terminate inflamm (IL10, TGFB)
64
Mechanism of lymphocytes trafficking
Express L-selectin = migre in blood = enter 2nd lympho organs through high endothelial venules (HEV = produce CCL19, CCL21, CXCL12, CXCL13) = attract naive LT et LB expressing CCR7 (CCL19-21-R) and CXCR4 (CXCL12-R) and/or CXCR5 (R-CXCL13) Only Peyer’s patch HEV express MadCAM1 = receptor for a4B7 adhesion expressed on LT and LB S1P accumulate in lymphatic vessels (R- on LT, LB, NK-t, macro)
65
Differenciation of dendritic cells
- Immature DC (CD34+, CCR1, CCR5) migre to exposure -> Exposed to TNFa or TLR -> DC express CCR7 -> migrate in blood until recruited by HEV where lympho express CCL19, CCL20 - Migration under influence of cytokines +++CCL21 - Recruited by CCL3 et CCL4 released from lympho and macro - Exposed to TNFa or TLR -> DC express CCR7 -> migrate in blood
66
Action of hepcidin and thrombopoietin
Hepcidin = small protein that reduces availability of iron to erythroid progenitors in bone marrow = anemia of chronic inflammation Thrombopoietin = growth factor for megakaryocyte = thrombocytosis
67
Mechanism of tissue proliferation
Priming phase = mediated by IL6 produced by Kupffer (if liver) = compentent to receive GF Growth factor phase = HGF, TGFa act on hepatocytes to activate gene transcription Terminal phase = return to quiescence (TGFB)
68
Angiogenesis steps
1. VasoD (NO, VEGF) 2. Proteolysis of ECM, separe pericytes = vessel sprout 3. Migration of immature endothelial cells 4. Proliferation of endo cells to form solid endothelial tubules 5. Maturation of endo cell, formation of lumina 6. Formation of stalk cells and tip cells at the end of vascular buds 7. Endo cells adhesion to adjacent cells and basal lamina and express R/ligands for leuco adhesion 8. Recruit pericytes and smooth muscle to support 9. Suppress endo proli/migration and end deposition of basement membrane
69
Role of these molecules in angiogenesis : 1. VEGF (++A) 2. FGF (+++FGF2) 3. Angiopoietin 1 et 2 4. PDGF and TGFB 5. Notch signaling
1. VEGF (++A) = migration/proliferation endo cells (sprouting), vasoD, formation of lumen 2. FGF (+++FGF2) = proliferation of endo cells, migration macro/fibroblasts + epithelial to cover wound 3. Angiopoietin 1 et 2 = GF = maturation of vessels 4. PDGF and TGFB = stabilize, connective tissue, recruit smooth muscle, suppress endo migration/prolif 5. Notch signaling = regulate sprouting and branching of new vessels (VEGF stimule Notch ligand)
70
Molecules involved in the degradation of collagen and other ECM component
MMP1 à 3 = cleave fibrillar collagen Gelatinase = degrade amorphous collagen and fibronectin Stromelysin = degrade numerous ECM components ADAM, cathepsin G, tPA, uPA
71
How does GC affect scarring?
Weaken scars due to inhibition of TGFB production and diminished fibrosis

Nutrition (13 decks)

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