Inflammation Flashcards
Which tight junction receptor prevents reverse transmigration of activated leukocytes back into a blood vessel?
JAM-C
4 actions of bradykinin as it relates to acute inflammation
Vasodilation, increased vascular permeability, smooth muscle contraction, pain
All leukotrienes increase vascular permeability, which one also causes vasodilation and is chemotactic for neutrophils and which one is which one causes smooth muscle contraction?
LTB4 is chemotactic
LTD4 causes smooth muscle contraction
Two actions of histamine?
vasodilation and increased vascular permeability
What effect do fibrinopeptides and FDPs have on the vasculature?
increase vascular permeability
Three big actions of PGE2 as it relates to inflammation?
Increased vascular permeability, fever, pain
4 main actions of IL1 and TNF as it relates to inflammation?
increase vascular permeability, chemotaxis, nausea, fever
Which is the main prostaglandin that causes inflammation?
PGD2
Two main actions of PAF as it relates to acute inflammation?
increases vascular permeability and causes smooth muscle contraction
C3a and C5a are anaphylotoxins - which one also causes smooth muscle contraction and which one causes leuokocyte chemotaxis?
C3a causes smooth muscle contraction, C5a causes leukocyte chemotaxis
Method by which albumin, LDLs, MMPs, and insulin enter the cell?
Transcytosis
Method by which water and ions enter the cell?
Paracellular passage
retraction of endothelial cells during acute inflammation occurs in which types of vessels?
venules
which factors mediate retraction of endothelial cells during acute inflammation?
histamine and NO
In which vessels does increased transcytosis occur during acute inflammation and what mediates it
Venules - VEGF
increased permeability due to cytoskeletal reorganization occurs in which vessels and is mediated by what?
postcapillary venules/some capillaries, mediated by IL-1, TNF, hypoxia
5 steps of leukocyte adhesion cascade in order
Margination, rolling, activation, stable adhesion, transmigration
mediator of rolling adhesion
Selectins
P-selectin is stored in which platelet granules?
Weibel palade bodies - alpha granules
receptors for selectins?
Sialyl-Lewis
Activators of neutrophils during the leukocyte adhesion cascade (7 things)
IL-1, TNF, IL-6, PAF, PDGF, C5a, IL-8
role of ADAM17 during the leukocyte adhesion cascade?
cleaves L-selectin from neutrophils so they can express integrins for stable adhesion
ESL, PSGL-1 are receptors involved in which phase of the leukocyte adhesion cascade?
Rolling
PECAM-1 (CD31) is involved in which stage of the leukocyte adhesion cascade?
transmigration
Mediates adherence of non-activated leukocytes to HEVs in LNs
L-selectin, and VLA4 to VCAM1
5 cytokines/gfs that maintain neutrophil numbers in health?
IL-1, TNFa, IL-3, GM-CSF, G-CSF
principle opsonin receptors on neutrophil membranes
CR1, CR2, Fc
the process by which the reduced form of NADPH oxidase is formed?
respiratory burst
SNARE proteins mediate which part of phagocytosis?
phagosome:lysosome fusion
myeloperoxidase converts H202 to what?
hypochlorous acid
Neutrophil granule content that inhibits growth of bacteria by sequestering free iron?
Lactoferrin
Myeloperoxidase is more abundant in which neutrophil granules?
Primary (azurophilic)
lactoferrin, lysozyme and MAC-1 are more abundant in which neutrophil granules?
Secondary (specific)
Gelatinase (MMP-9) and CRISP-3 are components of which neutrophil granules?
Tertiary granules
cattle and sheep neutrophils have less of which enzyme?
Lysozyme
Deoxyadenosine produced by staph aureus can degrade NETs and induce apoptosis via which caspase?
3
CCL5 and CCL11 are chemotactic for which leukocyte?
eosinophils (RANTES and eotaxin)
which granulocyte contains histaminase?
Eosinophils
factor which promotes the differentiation of a CD34 precursor cell into a basophil or a mast cell?
SCF
Two main cytokines released by basophils
IL-4, IL-13
Leukocyte that expresses high affinity IgE receptor?
basophil
which subset of mast cells are Th2 dependent?
mucosal
cytokines released by mast cells?
IL-5, IL-6, IL-15
what molecule down-regulates the release of substance P?
histamine
CD161+, CD3-, CD56+
Type 1 NK cells
CD161+, CD3-, CD56-
Type 2 NK cells
produced by type 1 NK cells
IFN-y (Th1 response)
produced by type 2 NK cells
IL-4, IL-5, IL-13 (Th2 response)
Main regulator of NK cell differentiation?
IL-21 (causes up regulation of CD16)
CD marker necessary for ADCC and IFN-y release by NK cells?
CD16
cytokines that stimulate NK cell proliferation (5 things)
IL-4, IL-12, IL-15, IL-21, Flt3 ligand
CD molecule recognized by NK-T cells?
CD1d
cytokines/factors released by NK-T cells (3 things)?
IL-4, IFN-y, GM-CSF
ITAM binds which Fcy receptor? does it promote macrophage activation or inhibition?
ITAM - FCyRI - activation
ITIM binds which Fcy receptor? does it promote macrophage activation or inhibition?
ITIM - FCyRIIB - inhibition
5 preformed inflammatory mediators
Histamine, bradykinin, substance P, neurokinin, serotonin
Which cellular granules contain histamine?
mast cells, basophils, platelets
Leukocyte histamine receptors
H1 and H4
gastric mucosa histamine receptors
H2
Nerve fiber histamine receptors
H3
endothelial histamine receptor
H1
Does tissue Kallikrein act on LMWK or HMWK to produced Bradykinin?
can act on either
does plasma Kallikrein act on LWMK or HMWK to produce bradykinin?
HMWK
Which kinin pathway is activated by the intrinsic coagulation pathway?
Plasma kinin pathway
Bradykinin receptor in inflamed tissue
B1R (B2R in normal tissue)
C1INH (alpha 2 macroglobulin) inhibits what?
plasma kallikrein
complement pathway activated by IgG or IgM x-linking C1?
classical
Proteolytic C1 component
C1r
C1 component cleaved by C1r
C1s
C1 component that binds Fc region of ab
C1q
complement pathway activated by microbial products, Kallikrein, plasmin, FXII
alternative
product of classical pathway C3 convertase
C3a
product of alternative C3 convertase
C3b
product of classical and alternative C5 convertase
C5a
ficolins activate which complement pathway?
MBL
Complement pathway in which MASPs cleave C4 and C2
MBL pathway
Disease: loss of C1 inhibitor
angioedema
Disease: loss of C1q
SLE
Product of phospholipase A2?
Arachidonic acid
substrate and product(s) of COX-1
arachidonic acid - phospholipases and thromboxanes
substrate and products of lipoxygenase?
arachidonic acid - leukotrienes and lipoxins
major prostaglandin produced by mast cells
PGD2
which prostaglandins increase vascular permeability?
PGD2 and PGE2
are most leukotrienes vasodilatory or vasoconstrictive?
vasocontrictive but increase vascular permeability
main leukotriene released by mast cells and eosinophils?
LTC4
action of 5-HPETE and 5-HETE?
neutrophil chemotaxis
are resolvins anti-inflammatory or pro-inflammatory?
anti-inflammatory
which cytokines are hematopoietic growth factors, in addition to GM-CSF and G-CSF?
IL-3, IL-9 (also involved in T-lymph development), IL-11
which type of Th response is seen during granulomatous inflammation from mycobacterial infection?
Th1
Cytokines that promote a Th2 response
IL-4, IL-6
cytokines that promote a Th17 response
IL-6, IL-23, TGF-b
type of Th response seen with autoimmune disease
Th17
cytokine that drives a Treg response?
TGF-b
cytokines that drive a T-FH response?
IL-6 and IL-21
Transcription factors for T-FH response
BCL-6 and cMAF
cytokine produced by a T-FH response
IL-21
role of T-FH response
drives b-lymphocyte development and Ab responses
which prostaglandins are vasoconstrictors?
PGF2 and TXA2
cytokine signaling via JAK/STAT is regulated by which protein?
SOCS
type of IFN produced by hematopoetic cells/plasmacytoid dendritic cells
IFNa
type of IFN produced by respiratory and intestinal epithelial cells
type III IFN
Receptors for HMGBP-1
RAGE, TLR2, TLR4
C chemokines
Lymphotaxin - XCL1
CC chemokines
recruit most leukocytes except neuts
CXC chemokines
neut chemotaxis - CXCL8 = IL-8
CX3C chemokine
Fractalkine
what effect does NO have on mast cells?
inhibits mast cell induced inflammation
TLR for lipotechoic acid
TLR2
TLR for flagellin
TLR5
TLR for bacterial ribosomal RNA
TLR13
TLR for profilin
TLR11/12
intracellular PRR for DNA
TLR9 (and AIM2)
itnracellular PRR for dsRNA
TLR3
intracellular PRR for ssRNA
TLR7/8, RIG-1, MDA5
LPS bound to which protein initiates endocytosis?
LPB then CD14
LPS bound to which protein initiates cytokine and inflamasome responses?
LPB then TLR4
NOD receptor present on hematopoietic cells and intestinal cells?
NOD2
three things in the inflammasome
NLR, ASC-1, caspase 1
three cytokines released by the inflamasome
IL-1b, IL-18, IL-33
PRR for paramyxovirus and influenza virus?
RIG-1
PRR for picornavirus?
MDA-5
Gasdermin is associated with which form of cell death?
pyroptosis
which complement components are acute phase proteins?
C3 and C4
Maresins, hydrogen sulfide, annexin A1, adiponectin all have what effect on inflammation?
anti-inflammatory
anti-inflammatory mediator which inhibits neutrophil migration across cell walls
resolvins
anti-inflammatory mediators that contribute to wound repair and reduce nerve sensitivity to pain
Maresins
anti-inflammatory mediator that promotes neutrophil apoptosis
hydrogen sulfide
anti-inflammatory mediator that is anti-apoptotic
adiponectin
SIRPa binds which cell surface marker to inhibit macrophage phagocytosis?
CD47
diffuse (leprotamous) granulomas are biased toward which Th response?
Th2
nodular (tuberculoid) granulomas are biased toward which Th response?
Th1
are sarcoids in horses granulomas?
no
Bovine papillomavirus E5 contributes to pathogen persistence via which mechanism?
down regulation of MHC class I
Receptor ligand pairing on monocytes in non-inflamed tissue
CX3CRI + Fractalkine (CX3CL) and CCR5 + MIP1a (CCL3)
receptor ligand pairing on monocytes in inflamed tissue
CCR2 + MCP-1 (CCL-2)
inducer of classically activated macrophages
IFN-y by Th1 lymphocytes + NK lymphocytes, and TNF from APCs
Itaconate secreted by which type of macrophages?
M2 (regulatory)
main activator of M2 macrophages?
IL-4 (and IL-13?)
main cytokines produced by classically activated macrophages?
IL-1, IL-12, IL-23
Fc receptor that inhibits macrophages?
FcyRIIB
CD molecules associated with formation of multinucleated giant cells?
CD44 and CD47
inhibitor of NF-kB released by macrophages
PPAR
dendritic cell growth factor
flt3 ligand
chemokine that promotes dendritic cell migration to LNs
CCL21
marker on mature DCs
CCR7
activator of NK cells
type 1 IFN and IL-12
Three components of CARs
T lymph anergy, lymphocyte apoptosis, decreased macrophage activation
growth factors that promote rapid hyperplasia of overlying epithelium in the proliferation phase of wound healing
EGF, HGF, FGF, VEGF + IL-1 and TGF-b
which GF induces the formation of myofibroblasts from fibroblasts?
TGF-b
keeps stem cells in a quiescent state
BMP
molecule released from active stem cells that induces proliferation of the quiescent cells?
B-catenin
PDGF, MMPs, and TIMPs are most active in which phase of wound healing?
remodeling
EGF, HGF, VEGF are most active in which stage of wound healing?
Proliferation
role of ADAM?
metalloproteinase - degrades lots of stuff
which part of the ECM gives it pliability and elasticity?
proteoglycans
which part of the ECM gives it tensile strength
collagen
senescent fibroblasts secrete which GF?
PDGF
Rho signaling
induces contractility in myofibroblasts
Angiopoietin receptor
Tie 2
factor involved in vascular stabiliization/recruitment of periceytes and smooth muscle cells
Angiopoietin 2
Lymphangiogenic factors
VEGF-C and PROX-1
During angiogenesis, how is lymphangiogenesis inhibited?
BMP inhibits PROX-1
Key initiator of wound repair in skin and lung epithelia?
FGF-10
induces production of surfactant proteins in the lung
TTF1
stimulates cilia formation in the lung
HFH-4
ligand for VLA-4
VCAM1
ligand for LFA-1 and MAC-1
ICAM-1
major inhibitor of neutrophil elastase
alpha 1 antitrypsin (also alpha 2 macroglobulin)
is serotonin a vasodilator or vasoconstrictor?
vasocontrictor
prevents formation of C3 convertase
DAF
inhibitor of the alternative pathway of complement by destroying C3b
Factor H
stimulates CRP and fibrinogen synthesis
IL-6
stimulates SAA synthesis
IL-1 and TNF
Protein involved in anemia of chronic disease by reducing iron availability to erythroid progenitors?
Hepcidin
main cytokine involved in priming stage of hepatocyte regeneration
IL-6
MMP that degrades fibrillar collagen
interstitial collagenases
Function of neuraminidase
Sialic acid degradation
Which adhesion molecule is used by T lymphocytes to migrate to selective sites in lymphoid tissues?
CD44
toxin produced by anthrax?
lethal factor
Target cells for feline acquired immunodeficiency virus express which of the following receptors?
CD134
