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Gen Path > Complement System, Chemical Mediators, Angiogenesis > Flashcards

Complement System, Chemical Mediators, Angiogenesis Flashcards

1
Q

What functions do cleavage products of complement have? (3)

A

Increased vascular permeability
Chemotaxis
Opsonization

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2
Q

What is the critical step in complement activation?

A

Cleavage of C3

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3
Q

What triggers the classical pathway? Next steps

A

Binding of C1q to antibody bound to antigen; C1r cleaves C1s, form C3 convertase with C2 and C4

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4
Q

What triggers the alternative pathway? Next steps

A

Microbial surface molecules (no antibody!); Factor B and Factor D form C3 convertase with C3b

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5
Q

What triggers the lectin pathway? Next steps

A

Plasma mannose-binding lectin bound to carbs on microbes; MASP-2 cleaves C4 and C2 to activate pathway

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6
Q

End result of all three complement pathways; possible outcomes (3)

A

C3b deposited on microbe; C3a and C5a recruits and activates leukocytes, C3b on microbe is bound by phagocyte C3b receptor for phagocytosis, formation of MAC

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7
Q

What splits C3 into C3a and C3b?

A

C3 convertase

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8
Q

What makes up the MAC?

A

C5b+C6-C9

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9
Q

How do C3a and C5a cause inflammation?

A

Both stimulate histamine release (anaphylatoxin)
C5a chemotactic for leukocytes
C5a activates lipoxygenase pathway in leukocytes

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10
Q

Decay accelerative factor (DAF) MOA

A

Prevents formation of C3 convertase

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11
Q

CD59 MOA

A

Inhibits formation of MAC

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12
Q

Complement factor H MOA

A

Inhibits alternative pathway by promoting cleavage of C3b and turnover of C3 convertase

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13
Q

In classical complement, what binds the Fc portion of antibody? What protein cleaves what?

A

C1q; C1r cleaves C1s

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14
Q

What makes up C3 convertase?

A

C4bC2a

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15
Q

Other than microbial products, what can trigger the alternative pathway by cleaving C3?

A

Other plasma proteins- kallikrein, plasmin, activated factor XII

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16
Q

Loss of what is associated with SLE? Mechanism?

A

C1q; loss of CD8 T cell regulation by C1q

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17
Q

What two special roles does C1q have?

A

Opsonization of apoptotic cells for phagocytosis
Regulation of CD8 T cells (self-tolerance)

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18
Q

How does complement induce antibody production?

A

B cells have receptors for C3b and C4b

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19
Q

Which complement proteins induce cleanup by phagocytosis?

A

C1q, C3, C4

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20
Q

Two major vasoactive amines

A

Histamine and serotonin

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21
Q

Histamine effect on arterioles vs venules?

A

Vasodilation vs increased permeability

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22
Q

Major effect of serotonin

A

Vascular permeability

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23
Q

Where are each of the histamine receptors found?

A

H1- endothelial cells and leukocytes
H2- gastric mucosa
H3- nerve terminals
H4- leukocytes

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24
Q

What enzyme forms leukotrienes? What do they generally do? What is the exception?

A

5-lipoxygenase; increased vascular permeability, bronchospasm, vasoconstriction; LTB4 causes chemotaxis

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25
What enzyme forms prostaglandins? What do they generally do? What is the exception?
Cyclooxygenase; vasodilation, increased permeability, inhibit platelet aggregation; TXA2 causes vasoconstriction, promotes platelet aggregation
26
Which prostaglandin is primarily synthesized by mast cells? Which one is more widely distributed
PGD2; PGE2
27
Which prostaglandin is hyperalgesic?
PGE2
28
What is the major prostaglandin produced by platelets?
Thromboxane A2
29
What is the major prostaglandin produced by endothelial cells?
Prostacyclin PGI2
30
What is unique about lipoxins?
Synthesized in neutrophils, activated in platelets
31
What class of chemokines is attractant for neutrophils? Specific one and its receptor
CXC CXCL8 (IL-8) binds CXCR2
32
What class of chemokines attracts anything but neutrophils? Monocyte chemokine and receptor? Eosinophil? Macrophage?
CC CCL2 (MCP-1) binds CCR2 CCL11 (eotaxin) binds CCR3 CCL3 (MIP-1alpha) binds CCR1
33
What class of chemokines attracts lymphocytes? Example and receptor?
C XCL1 (lymphotactin) binds XCR1
34
What class of chemokines attracts monocytes and T cells? Example?
CX3C CX3CL1 (fractalkine) binds CX3CR1
35
What type of receptor do chemokines use?
G protein coupled receptor
36
Functions of PAF
Platelet aggregation Vasoconstriction Bronchoconstriction
37
Role of PARs in inflammation?
Found on leukocytes, also activated by thrombin, link between coag and inflammation
38
What are kinins, where do they come from? What inactivates them?
Vasoactive peptides from kininogens (in plasma) that are cleaved by kallikreins (proteases); kininase
39
Primary example of kinin; function? Receptor in normal and inflamed tissue
Bradykinin; vascular permeability, dilation, pain (histamine-like); B1r in inflamed, B2r in normal
40
What is the main example of a neuropeptide? Where is it prominent?
Substance P; GI and lungs
41
Purpose of substance P
Pain signals Vascular permeability Activation of mast cells
42
Affect of histamine on substance P
Negative feedback via H3 receptors
43
How does angiogenesis start? What two mediators are involved?
NO causes vasodilation VEGF causes increased permeability
44
What allows formation of a vessel sprout?
Separation of pericytes and breakdown of BM
45
What stimulates the production of VEGF?
HIF-1alpha (hypoxia) PDGF TGF alpha
46
What is FGF-2's role in angiogenesis?
Stimulate proliferation of endothelial cells (along with VEGF), promote migration of macs and fibroblasts for healing
47
What is Ang 1 and Ang 2's role?
Ang 1- Stage 2 proliferation Ang 2- Vascular remodeling, maturation
48
What is PDGF's role? TGF beta?
Recruits smooth muscle; suppresses endothelial proliferation and migration, ECM protein production (stabilizes new vessel)
49
What regulates the sprouting and branching of new vessels? How?
Notch pathway; VEGF-A binds VEGF-R2, stimulates tip to express Notch ligand DII4, which binds Notch receptors in stalk, causing stalk cells to reduce VEGF-R expression
50
What inhibits binding of Notch receptor by DII4
Jagged
51
What kind of receptor is the VEGF receptor?
Tyrosine kinase receptor
52
What stimulates MMP release? What inhibits MMP release? What activates MMPs? What inhibits activated MMPs?
GFs and cytokines; steroids, TGF-beta; plasmin; TIMPs
53
What ligand and receptor mediate migration of endothelial cells?
alpha5beta3 integrin on endothelial cells bind fibrin/fibronectin in ECM
54
What ligand and receptor mediate second stage of proliferation (periendothelial cell recruitment)
ANG-1 binds Tie-2
55
What ligand and receptor mediate remodeling of the vessel?
Ephrin B2 binds EphB4
56
Which growth factor stimulates granulation tissue formation?
EGF
57
Which GFs stimulate hepatocyte and epithelial proliferation
TGF alpha and EGF (related) HGF (scatter factor)
58
Which GF (2) is produced by fibroblasts?
Hepatocyte Growth Factor (scatter factor) Keratinocyte Growth Factor aka FGF 7
59
Which GF is only produced by mesenchymal cells?
VEGF
60
Which GF is chemotactic for neutrophils and many other cells?
PDGF
61
What does FGF-10 do?
Epithelial call differentiation in wound repair
62
What is different about TGF-beta receptors?
They are serine-threonine kinase receptors that induce phosphorylation of Smad transcription factors
63
Main effects of TGF beta
Stimulate production of collagen and matrix proteins Decrease MMPs, increase TIMPs Drives fibrosis in chronic inflammation Antiinflammatory cytokine
64

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