Term
| Which cells are first to reach periphery tissue during trauma/infection? |
|
Definition
|
|
Term
| What are the bird version of neutrophils? |
|
Definition
|
|
Term
| What are the roles of neutrophils? (4) |
|
Definition
Effector Functions:
-phagocytosis
-degranulation
-extracellular traps
Regulatory Functions
-recruit circulating monocytes |
|
|
Term
| Where do granulocytes originate from? |
|
Definition
| bone marrow-equivalent tissues |
|
|
Term
| What is required for general granulocyte differentiation? What do neutrophils require in addition? |
|
Definition
GM-CSF, G-CSF, IL-3, IL-6
Neut. require IL-8 |
|
|
Term
| What is the typical lifespan of a human neutrophil? |
|
Definition
|
|
Term
MPO+ granules are referred to as...
MPO- granules are referred to as... |
|
Definition
primary / azurophil granules
secondary / specific granules |
|
|
Term
| What determines the contents of a granule? |
|
Definition
| expression of different genes at different stages of maturation |
|
|
Term
| What enzymes are found in azurophil granules? (5) |
|
Definition
PELMC
Proteinase 3
Elastase
Lysozyme
MPO
Cathepsin G |
|
|
Term
| What does azurophil elastase do? |
|
Definition
| important for adhesion between neutrophil & endothelial cells |
|
|
Term
| What does azurophil Cathepsin G do? |
|
Definition
| bactericidal, involved in tissue remodeling |
|
|
Term
| What does azurophil Proteinase 3 do? |
|
Definition
| activates nearby cells to secrete monocyte chemokines |
|
|
Term
| What does azurophil MPO do? |
|
Definition
|
|
Term
| What does azurophil lysozyme do? |
|
Definition
| destroys peptidoglycans of Gram+ bacteria |
|
|
Term
| What cationic proteins are found in azurophil granules? |
|
Definition
|
|
Term
| What do specific (secondary) granules contain? (5) |
|
Definition
LATCH
Lactoferrin
Adhesion molecules
TNF receptors
Collagenase
Haptoglobin |
|
|
Term
| What do gelatinase granules contain? (5) |
|
Definition
TAMAL
TNF Receptors
Adhesion molecules
Matrix metalloproteins
Arginase
Lysozyme |
|
|
Term
| What are the final type of neutrophil granule to be packaged? |
|
Definition
| tertiary gelatinase granules |
|
|
Term
| When are gelatinase granules released during neutrophil migration? |
|
Definition
| During trans-endothelial cell migration |
|
|
Term
| What are the general steps of neutrophil adhesion & migration, and the enzymes/proteins involved? |
|
Definition
1. Tethering
P-selectin & L-selectin
2. Margination / rolling
PAF, ICAM 1&2, B2 integrin, elastase, leukosialin
3. Increased adhesion
E-selectin & P-selectin, ICAM1&2, B2 integrin, TNF-alpha
4. Trans-endothelial migrations
proteases |
|
|
Term
| What are the stages of neutrophil phagocytosis? |
|
Definition
Chemotaxis
Adhesion & Opsonization
Ingestion
Destruction |
|
|
Term
| Describe what happens during the first stage of neutrophil phagocytosis |
|
Definition
-chemokine gradients draw neutrophils to affected tissue
-lamellipodia detect the chemokines & direct neutrophil movement |
|
|
Term
| Are opsonins positive or negatively charged? Are they innate or acquired? |
|
Definition
positive
can be part of the innate & acquired immune systems |
|
|
Term
| Why do fish rely heavily on innate opsonins, more so than mammals? |
|
Definition
-smaller variety of immunoglobulins
-cold temperatures are not conducive to developing an acquired immune response |
|
|
Term
True or False
Fish & chickens do not ingest colostrum and therefore do not benefit from passive immunity |
|
Definition
False
Nutrients and maternal acquired opsonins are passed via the yolk sac |
|
|
Term
| What are the innate opsonins? (5) |
|
Definition
MLSCC
-MBL
-Lysozyme
-Serum amyloid A
-C-reactive protein
-C3 breakdown products |
|
|
Term
| What are the acquired opsonins? |
|
Definition
Igs via Fc receptors
IgM+ via C1q receptor |
|
|
Term
| Does phagocytosis always require opsonins? |
|
Definition
|
|
Term
| What happens during the 3rd stage of neutrophil phagocytosis? |
|
Definition
Ingestion
-pseudopodia surrounds particle, forming a phagosome
-phagosome + azurophil granule combine to form a phagolysozome |
|
|
Term
| What happens during oxygen-dependent killing |
|
Definition
1. NOX complex activated (respiratory burst)
2. NOX converts NADPH -> NADP +2e, electrons bind to O in mmb = superoxide anions
3. Superoxide anions -> H2O2 via SOD
4. H2O2 reacts with Cl- in presence of MPO producing toxic hypochlorite
5. H2O2 also reacts with Fe to form OH- free radicals |
|
|
Term
| What protects neutrophils from H2O2 during oxygen-dependent killing? |
|
Definition
Hydrogen peroxidase converts H2O2 to water & oxygen
Glutathione (GSH) reduces oxidants
Fe-binding proteins reduce iron bioavailability
e.g. lactoferrin & haptoglobin |
|
|
Term
True or False
Chickens lack MPO |
|
Definition
|
|
Term
| What happens during oxygen-independent killing? |
|
Definition
-pH is lowered, increasing lytic enzyme activity
-a/B defensins & cathelicidins interact with negatively charged membrane components, disrupting membrane integrity |
|
|
Term
| What are the lytic enzymes activated during oxygen-independent killing? |
|
Definition
PLACE
Proteases
Lysozyme
Acid hydrolases
Cathepsin G
Elastase |
|
|
Term
True or False
Neutrophils constitutively express membrane receptors |
|
Definition
False
Not until they have entered their target tissues |
|
|
Term
| What cells express defensin genes? |
|
Definition
keratinocytes
mucosal epithelial cells
azurophil granules |
|
|
Term
| Which animals express alpha-defensin genes? |
|
Definition
|
|
Term
| What makes pigs unique in terms of antimicrobial peptide gene expression? |
|
Definition
| they have a large number of cathelicidin genes |
|
|
Term
| How are defensins activated? |
|
Definition
| pre & pro pieces must be cleaved off |
|
|
Term
| What are the roles of defensins (5) |
|
Definition
-disrupt microbial surfaces
-chemoattractants
-induce apoptosis of infected host cells
-anti-inflam (sequester LPS & LTA)
-antiviral |
|
|
Term
| What are neutrophil extracellular traps composed of? |
|
Definition
-nuclear chromatin
-histones
-antimicrobial granule cargo |
|
|
Term
True or False
In NETosis, the plasma membrane is destroyed |
|
Definition
|
|
Term
| When do neutrophils release extracellular traps? |
|
Definition
-when dying (use nuclear chromatin)
-also from viable cells (use mitochondrial chromatin) |
|
|
Term
| How is NETosis different from apoptosis? |
|
Definition
-plasma mmb is left intact
-caspases are not involved
-DNA does not become fragmented |
|
|
Term
| How do neutrophils regulate the inflammatory immune response? (4) |
|
Definition
-secrete chemokines (e.g. CCL4) which attract monocytes & DCs
-secrete signals that determine whether macrophages are pro or anti inflammatory
-Cathepsin G activates humoral chemerin
-TNF alpha activates DC & macrophages, also triggers differentiation
-IFN gamma drives T cell differentiation & macrophage differentiation |
|
|
Term
|
Definition
| attracts DCs and macrophages |
|
|
Term
| How do neutrophils regulate resolution? |
|
Definition
| -secrete pro-resulution molecules which stop neutrophil influx & promote monocyte influx |
|
|
Term
| What are the pro-resolution molecules? (3) |
|
Definition
lipoxins
resolvins
protectins |
|
|
Term
| How do neutrophils generate lipoxins? |
|
Definition
| from arachidonic acid, using LOX |
|
|
Term
| How do neutrophils generate resolvins & protectins? |
|
Definition
| from w-3 fatty acids using LOX, COX & cytochrome P450 |
|
|
Term
| Neutrophils are capable of producing large amounts of which anti-inflammatory interleukin? |
|
Definition
|
|
Term
| What is the 'hallmark of inflammatory tissue resolution'? |
|
Definition
| clearance of apoptotic neutrophils by macrophages, or their removal at mucosal surfaces |
|
|
Term
| What do HIF1 and FOXO3a do? |
|
Definition
| postpone neutrophil apoptosis |
|
|
Term
| What triggers clearance of apoptotic neutrophils? |
|
Definition
-release of thrombospondin 1 attracts macrophages
-lysophosphatidylcholine & phosphatidylserines are exposed after the cell becomes inverted
-this triggers scavenger-receptor mediated phagocytosis |
|
|
Term
| How does phagocytosis of neutrophils by macrophages prevent further neutrophil production & release? |
|
Definition
-phagocytosis slows IL-23 production
-this slows down IL-17 release from secondary lymph tissues
-lack of IL-17 downregulates bone marrow production of G-CSF
(G-CSF is a requirement for neutrophil production) |
|
|
Term
| What must be present in order for H2O2 to react with halides to form products which oxidize cell membranes? |
|
Definition
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