Term
| What are the 2 general functions of sentinel cell products? |
|
Definition
-trigger local inflammation
-initiate acquired immunity |
|
|
Term
| What are the 4 products of sentinel cells? |
|
Definition
pro-inflammatory cytokines
reactive oxygen species
chemokines
vasoactive molecules |
|
|
Term
| What are the cardinal signs of local inflammation? |
|
Definition
|
|
Term
| What happens if sentinel cell products enter circulation? |
|
Definition
-acute phase response is initiated
(fever, sickness etc) |
|
|
Term
| Acute phase proteins that are either induced or inhibited during the acute phase response are produced by what organ? |
|
Definition
|
|
Term
| Which cytokines are pro-inflammatory? |
|
Definition
|
|
Term
| What are the pleotropic effect of pro-inflam cytokines? |
|
Definition
pyrogenic
induce production of APP
increase vascular permeability
activate B & T cells |
|
|
Term
| How are pro-inflam cytokines regulated? |
|
Definition
-controlling expression of the cytokine genes & their receptors
-storing cytokines as precursors which must be activated
-repression mRNA translation & promoting mRNA degradation of pro-inflam cytokines through the binding of miRNA |
|
|
Term
True or False
miRNA show a lot of variation from species to species |
|
Definition
false
they are highly conserved |
|
|
Term
True or False
miRNA can induce production of pro-inflam cytokines |
|
Definition
|
|
Term
| The expression of miRNA is specific to _______ and ________ |
|
Definition
|
|
Term
| Is TNF-alpha membrane bound or secreted? |
|
Definition
|
|
Term
| How is the secreted form of TNF-alpha produced? |
|
Definition
| membrane TNF-alpha is cleaved by ADAM17 |
|
|
Term
| What do membrane bound & secreted TNF-alpha do in terms of communication? (3) |
|
Definition
-cell to cell signaling
-autocrine signaling
-paracrine signaling |
|
|
Term
| TNF-alpha can trigger the production of _____ and ____ |
|
Definition
|
|
Term
| What is the first pro-inflam cytokine produced during the inflammatory response? |
|
Definition
|
|
Term
| What inhibits the prolonged production of IL-1 & IL-6 |
|
Definition
| short half-life of TNF-alpha |
|
|
Term
| What can be done to extend the effect of TNF-alpha in mast granules? |
|
Definition
| stabilization with heparin |
|
|
Term
| What regulates TNF bioactivity? |
|
Definition
heparin in mast granules
TNFR1 receptor (binds soluble & mmb bound TNF)
TNFR2 receptor (only on immune cells, responds to mmb bound TNF) |
|
|
Term
| Which TNF reeceptor is found only on immune cells? |
|
Definition
|
|
Term
| Is IL-1 alpha membrane bound or secreted? |
|
Definition
|
|
Term
| How is IL-1 alpha activated? |
|
Definition
|
|
Term
| How is IL-1 beta activated? |
|
Definition
|
|
Term
| How is autophagy related to pro-IL-1 |
|
Definition
| recycling process by with pro-IL-1 is loaded into autophagosomes, & is degraded |
|
|
Term
| How is IL-1 function regulated? |
|
Definition
-expression of cytokine genes
-activation by calpain/caspase-1
-autophagy
-receptors |
|
|
Term
| How do receptors regulate IL-1 function? |
|
Definition
CD121a acts as a signaling receptor
CD121b reduces bioavailability of IL-1 beta & IL-1 alpha
competition with IL-1 beta & an IL-1 receptor agonist for ligation with CD121a |
|
|
Term
True or False
IL-1 can induce the secretion of IL-6 |
|
Definition
|
|
Term
| What causes the production of immunoregulatory glucocorticoids? |
|
Definition
| pro-inflam cytokines activating the hypothalmic-pituitary-adrenal-axis (HPAA) |
|
|
Term
| Where are GC receptors (GCR) found? |
|
Definition
|
|
Term
| What are the functions of GCR? (5) |
|
Definition
1. transcription factor: induces expression of IkB
2. inhibits transcription of other genes by tethering transcription factors e.g. NF-kB
3. inhibits transcription of pro-TNF alpha, IL-1 & IL-6
4. Inhibits phosphorylation ability of kinases
5. Suppresses or induces miRNA |
|
|
Term
| What effect does acetylcholine have on cytokines? |
|
Definition
| -shuts down their production, increases production of anti-inflam IL-10 |
|
|
Term
| Is IL-10 inflammatory of anti-inflammatory? |
|
Definition
|
|
Term
| How does acetylcholine increase IL-10 production? |
|
Definition
| via a7 nicotinic acetylcholine receptors on neutrophils & macrophages |
|
|
Term
| How does TNF-alpha promote inflammation? |
|
Definition
Induces:
1. Expression of neutrophil & endothelial cell molecules
2. Prod coagulation factors
3. Secretion of APP
4. Leukocyte migration
5. Production of IL1 & IL6
6. Production of chemokines eg. IL8 |
|
|
Term
| How does TNF-alpha activate epithelial cells? |
|
Definition
| increases vascular permeability & expression of adhesion molecules |
|
|
Term
| Apoptosis induced by TNF-alpha depends on what pathway? |
|
Definition
| caspase-dependent pathway |
|
|
Term
| TNF-alpha activates the CNS at the level of the _______ |
|
Definition
|
|
Term
True or False
TNF-alpha can induce fever/sickness/septic shock |
|
Definition
|
|
Term
True or False
TNF-alpha can induce eosinophil degradation |
|
Definition
|
|
Term
| Both ___ and ___ can induce expression of endothelial cell adhesion molecules |
|
Definition
|
|
Term
True or False
IL-6 has a shorter half life than TNF-alpha |
|
Definition
|
|
Term
| What mediates the pro-inflam response of IL-6? |
|
Definition
| cleave of mIL6R by ADAM17 to release soluble sIL6R |
|
|
Term
| What is the anti-inflam role of IL-6? What mediates this? |
|
Definition
induces IL-1RA and IL-10 production
mediated by IL-6 binding to mIL6R associated with GB130 |
|
|
Term
True or false
IL-6 contributes to increased production of Ig's |
|
Definition
|
|
Term
| IL-6 is considered a _____ |
|
Definition
| Th2 cytokine which favours the AbMIR |
|
|
Term
| What are the classifications of chemokines? |
|
Definition
CC (contiguous cysteine residues)
CXC |
|
|
Term
| What do CC chemokines typically act on? |
|
Definition
| macrophages & dendritic cells |
|
|
Term
Which of the following are important chemokines for macrophages
CCL2
CCL4
CCL7
CCL5 |
|
Definition
|
|
Term
|
Definition
|
|
Term
Which of the following are important chemokines for monocytes
CCL2
CCL4
CCL7
CCL5 |
|
Definition
|
|
Term
| What chemokines are important for neutrophils? |
|
Definition
|
|
Term
True or False
TNF-beta is chemotatic for neutrophils |
|
Definition
|
|
Term
| Why are TNF-alpha & C5a not considered true chemokines? |
|
Definition
| they have a different molecule structure |
|
|
Term
| Which chemokines have antimicrobial properties? |
|
Definition
|
|
Term
Which of the following receptors does RANTES (CCL5) bind to?
CCR1
CCR2
CCR3
CCR4
CCR5 |
|
Definition
|
|
Term
Which of the following receptors do CXCL chemokines bind to?
CCR1
CCR2
CCR3
CCR4
CCR5 |
|
Definition
|
|
Term
| Are chemokine receptors expressed constitutively or induced? |
|
Definition
| some are constitutive, some are induced |
|
|
Term
| What effects do vasoactive compounds have? |
|
Definition
-initially slow down local blood flow, allowing adhesion of granulocyytes to endothelium
-then dilation & increase in permeability to allow influx of cells |
|
|
Term
| What attracts blood platelets (thrombocytes) to a damaged blood vessel? |
|
Definition
| collagen & Von Willebrand Factor |
|
|
Term
| How are platelets activated? |
|
Definition
|
|
Term
| What vasoactive compounds have pro-inflam properties? (6) |
|
Definition
-histamine
-vasoactive lipids
-enzymes tryptase & chymase
-pro inflam cytokines
-chemotactic agents C5a
-platelet activating factor PAF |
|
|
Term
| What vasoactive compounds increase expression of adhesion molecules? (3) |
|
Definition
tryptase
PAF
pro inflam cytokines |
|
|
Term
| Which compounds increase vasodilation? (5) |
|
Definition
NO
tryptase
prostaglandins
C3a & C5a
kinins
substance P |
|
|
Term
| Which compounds increase vascular permeability (8) |
|
Definition
histamine
seratonin
prostaglandins
prostacyclin
leukotrienes
C3A & C5A
PAF
pro inflam cytokines |
|
|
Term
| What compounds increase platelet aggregation? |
|
Definition
thromboxanes
prostacyclins
collagen
Von Willebrand Factor |
|
|
Term
| What fatty acid is released from cell membrane phospholipids when mast cells degranulate? What happens to it? |
|
Definition
arachidonic acid
converted to eicosanoids |
|
|
Term
| Which enzymes convert AA to eicosanoids |
|
Definition
5-lipoxygenase (LOX) converts into leukotrienes
COX 1 & COX 2 converts into prostaglandins |
|
|
Term
| Which leukotriene is a neutrophil & eosinophil chemoattractant? |
|
Definition
|
|
Term
| Which cyclooxygenase is constitutively expressed? |
|
Definition
|
|
Term
| Which cyclooxygenase is inducibly expressed? |
|
Definition
|
|
Term
|
Definition
| inhibit further neutrophil influx from circulation |
|
|
Term
| Which complement protein is a neutrophil chemoattractant? |
|
Definition
|
|
Term
|
Definition
| produces kinins such as bradykinin which increase vasodilation, vascular permeability, pain, neutrophil activation |
|
|
Term
| What coagulation factors are involved with clot formation? |
|
Definition
|
|
Term
| Which hepatic zymogen has fibronylytic properties? |
|
Definition
|
|
Term
True or False
the products of fibrinolysis act as chemoattractants for neutrophils |
|
Definition
|
|
