L5: Innate Immunity II Flashcards
1
Q
DAMPs
A
damage associated molecular patterns
2
Q
PAMPs
A
pathogen associated molecular patterns
3
Q
exogenous ligands - PAMPs
A
nucleic acid - CpG, ds RNA
lipid A
protein PGN
4
Q
endogenous ligands - DAMPs
A
nucleic acid - ATP
lipid - oxLDL, saturated fats
protein - HSP, HMGB1
5
Q
necrosis
A
a passive, catabolic cell death in response to external toxic factors
6
Q
characteristics of necrosis
A
dirty form of cell death
swelling
cell rupture
may cause inflammation and harm neighbor cells
7
Q
inflammation is an ______ reaction.
A
innate
8
Q
inflammation is caused by ?
A
- increased blood to area
- increased capillary permeability
- influx of neutrophils
- arrival of monocytes/macrophages
- distortion of homeostasis/loss of function
9
Q
characteristics of inflammation
A
swelling pain redness heat loss of function
10
Q
HMGB1
A
high mobility group box 1
a protein passively released during necrosis
RAGE is its receptor
11
Q
functions of HMGB1
A
activates NF - kB pathway
12
Q
uric acid is another diffusible ______ signal that activates the ______ pathway.
A
danger signal
NF-kB pathway
13
Q
HSPs
A
danger signals
induce NF-kB pathway
release inflammatory cytokines
14
Q
epithelia are _____ barriers, produce _______ substances, and harbor intraepithelial ________.
A
physical
antimicrobial
lymphocytes – kill microbes and infected cells
15
Q
defensins
A
small cationic peptides
contain both cationic and hydrophobic regions
16
Q
what produces defensins?
A
epithelial cells of mucosal surfaces
granule-containing WBCs
neutrophils, nk cells, ctls
17
Q
synthesis of defensins is stimulated by _______ and ______ products via ____.
A
cytokines
microbial products
PRRs
18
Q
defensins have _____ toxicity to microbes - including ?
A
direct
bacteria, fungi, enveloped viruses
19
Q
how do defensins kill microbes?
A
inserting into and disrupting functions of microbial membranes
20
Q
what do defensins regulate?
A
activation of immune cells involved in inflammatory response to microbes
21
Q
cathe’licidins
A
antimicrobial peptides w/ microbicidal activity and chemotactic activity for immune cells
22
Q
cathe’licidins are produced by ?
A
neutrophils
barrier epi cells - skin, GI, respiratory tract
23
Q
cathe’licidins synthesis is stimulated by ?
A
cytokines
microbial products
24
Q
functions of cathe’licidins
A
direct toxicity to microorganisms
activation of WBCs
bind/neutralize LPS
25
mechanism for anti-inflammatory role of cathe'licidins
bind to DNA
| block inflammasome activation
26
CD
stands for 'cluster of differentiation'
indicates a defined subset of cellular surface receptors that id cell type and stage of differentiation
27
NK cell lineage
from adaptive lineage but are innate immunity cells
28
what do NK cells recognize?
various stressed cells
in absence or presence of abs
29
NK cell activation
triggered by their recognition
triggers:
lysis of cell
produce cytokines/chemokines
30
NK cells are biased to produce ?
IFN-gamma in most conditions
IL-10 in chronic/systemic inflammation
31
thru biological activities, NK cells participate in ?
shaping the secondary immune response
can boost or dampen macrophage and T cell responses
thru secretion of INF-y/IL-10
32
NK cells respond to _____ produced by macrophages and secrete _____ .
IL-12
INF-y
33
INF-y activates the macrophages to kill _______ microbes and stimulates productions of ____ in the cells.
phagocytized microbes
IL-12
34
NK cell activating receptors are called ?
KIRs
| killer cell immunoglobulin (IG) - like receptors
35
Inhibitory receptors of NK cells
these receptors recognize MHC I molecules
activate protein tyrosine phosphatases
inhibiting activation signals
36
due to inhibitory receptors, NK cells do not kill ?
class I MHC expressing cells
= healthy cell
these are receptors on NK cells that recognize MHC on target cell
37
NK cells recognize cellular stress and become activated via activating NKG2D receptors which bind to ______ and ______ ligands .
MICA
MICB
on the surface of stressed cells -- associated w/ viral infections and malignant transformation
38
NK cells also sense the ____ of cell surface molecules to determine if the cell is under too much stress>
density
39
steps in killing target cell by NK cells
1. NK release perforins - polymerize, form hole in enemy cell memb.
2. granzymes from NK enter thru hole and degrade enemy cell enzymes
3. enemy cell dies via apoptosis
4. macrophage engulfs and digests dying cell
40
define the complement system
it consists of several plasma proteins that work together to opsonize microbes
promote recruitment of phagocytes to site of infection
in some cases directly kill microbes
41
the complement system may be initiated by 3 distinct pathways
classical pathway
alternative pathway
lectin pathway
42
early step 1 -- complement system
formation of C3 convertase complexes
which produce C3a and C3b to trigger inflammation and opsonize microbes
43
early step 2 -- complement system
formation of C5 convertase complexes
which produce C5a and C5b which perpetuate inflammation and initiate late steps
44
late steps -- complement system
formation of memb. attack complexes
which form holes in microbial memb.
45
complement activation involves _______ cascades, in which inactive precursor enzyme called ______, is altered to become an active _______ that cleaves the next complement protein in the cascade.
proteolytic cascades
zymogen
protease
46
enzymatic cascades result in ?
tremendous amplification of the amount of proteolytic products that are generated
47
byproducts of complement activation
perform various effector functions of the complement system
48
the complement system works in ______ w/ other medically important proteolytic cascades.
cooperation
ex. coagulation pathway
49
recognition of microbes by any of the three complement pathways results in recruitment and assembly of complement proteins into ?
protease complexes
50
C3a fragment
stimulates inflammation by acting as a chemoattractant for neutrophils
51
C3b fragment
covalently attaches to microbial surface
serves as opsonin to promote phagocytosis of microbe
52
C3 convertase
cleaves C3 into a and b fragments
binds c3b fragment to form protease complex = C5 convertase
53
C5 convertase
cleaves C5 into c5a and c5b
54
C5a fragment
a very potent chemoattractant
also induces changes in permeability of BVs
55
C5b fragment
is attached to microbe memb.
initiates formation of complex of C6, C7, C8, C9 complement proteins
--called membrane attach complex MAC
56
multiples MACs cause ?
bacterial leak and lysis
57
the alternative pathway of activation is capable of ?
autoactivation
because of 'tickover' of C3
58
Tickover
occurs spontaneously at a rate of 1% of total C3 per hour
generating fragments a and b
59
alternative pathway -- C3b
capable of binding factor B
which is cleaved into Ba and Bb by active serum protease factor D
60
fragment Bb -- alternative pathway
associates w/ C3b and C3 convertase = C3bBb
capable of cleaving additional C3's generating more C3b
61
alternative pathway --- successive proteolytic steps is enhanced by ?
serum protein properdin
62
serum properdin
stabilizes protein-protein interactions during complement system
63
the alternative pathway can also be initiated as an _________ when fixed C3b that is generated via classical or lectin path binds to factor ___.
amplification loop
factor B
64
classical pathway is so called because ?
was discovered first
65
the classical pathway is ____ mediated .
ab
66
classic pathway -- C1q
a plasma protein
recognizes and binds to ag-ab complexes
binds to Fc portion of ab
67
classic pathway -- once C1q binds ?
2 associated serine proteases called C1r and C1s
become active
68
C1r activates _____ so that ?
C1s
so that it can activate C2 and C4
69
classical pathway C3 convertase
complex C4bC2a
70
classical pathway C5 convertase
C4bC2aC3b
71
the lectin pathway is triggered by ?
plasma protein -- mannose binding lectin MBL
has hexametric structure similar to C1q component of classical pathway
72
MBL recognizes ?
terminal mannose residues on microbial glycoproteins and glycolipids
73
after MBL binds to microbes?
2 zymogens called - MASP1 and MASP2
are activated
74
MASP1 and 2
similar functions to C1r/C1s
| initiate downstream proteolytic steps
identical to classic path
75
overview classical pathway
--requires IgM or IgG and C1
--C4bC2a is C3 convertase
--C4bC2aC3b = C5
76
overview lectin pathway
--does not use C1
--when MBP binds to bacteria -- MASPs are activated
- -C4bC2a = C3
- -C4bC2aC3b = C5
77
overview alternative pathway
--C3 undergoes spontaneous hydrolysis
--factors B and D needed
- -C3bBb = C3
- -C3bBbC3B = C5
78
MBL = ?
MANNOSE BINDING LECTIN
79
MASP = ?
MBL-associated serine protease
also called mannose-associated serine protease
80
complement pathway is not activated on the surface of _____ cells because they express?
mammalian cells
express regulatory proteins
which inhibit, disassemble, or cleave the convertases
81
DAF blocks ?
C2:C4b interaction
82
DAF or CR1 enhance dissociation of ?
C4bC2a interaction
83
CR1 and Factor I cleave ?
C4b and C3b
84
Factor I prevents ?
the assembly of C3 and C5 convertase
85
```
DAF = ?
CR1 = ?
FI = ?
```
decay-accelerating factor
complement receptor 1 = serves as cofactor for FI
factor I = C3b/C4b inactivator
the regulatory proteins expressed by mammal cells
86
complement functions
recruitment and activation of WBCs
formation of MAC to lysis microbe
C3b phagocytosis
87
soluble complement fragments:
C3a
C4a
C5a
3 = mast cell and basophil
4 = neutrophil
5 = monocyte/macrophage
88
some bacteria can survive in phagolysosomes because ?
they express catalase
89
after ingestion and formation of a phagolysosome, microbes are killed by ?
reactive oxygen and nitrogen species
and
proteolytic enzymes
90
tissue macrophages are activated by microbial products such as ___ and by NK cells via ?
LPS (TLR4)
IFN-y (cytokine receptor)
91
tissue macrophage activation leads to activation of ?
transcription factors
transcription of genes
synthesis of proteins
92
TNF and IL-1 act locally on _______ and _______ to induce acute inflammation.
leukocytes
endothelium
both cytokines also induce expression of IL-6 from WBCs
93
TNF, IL-1, and IL-6 mediate protective systemic effects of inflammation including induction of ?
fever
acute-phase protein synthesis by the liver
leukocytosis
94
define leukocytosis
increase production of leukocytes by the bone marrow
95
systemic TNF can cause pathologic abnormalities that lead to _____ shock and ?
septic shock
decreased cardiac function
thrombosis and capillary leak
metabolic abnormalities due to insulin resistance
96
pentraxin family
family of plasma proteins that recognize microbial structures
and participate in innate immunity
97
CRP and SAP are ?
C-reactive protein
serum amyloid P
acute phase proteins from the pentraxin family
98
plasma conc. of CRP and SAP are ______ in healthy individuals but can ?
very low
can increase up to 1000x during infections
also in response to inflammation
99
increased levels of CRP and SAP are a result of ?
increased synthesis by the liver
induced by cytokines IL-6 and IL-1
100
IL-6 and IL-1 are produced by ?
phagocytes as part of the innate immune response
101
CRP and SAP recognize ______ and _________, which are found on bacteria and apoptotic cells.
phosphorylcholine
phosphatidylethanolamine
102
how can CRP and SAP activate the complement system?
by binding C1q
and
initiating the classical path
103
upon viral infection, viral nucleic acids and proteins are recognized by several ?
cellular TLRs
104
TLR-mediated signaling activates transcription factors that stimulate the production of ?
type I interferons
| IFN-a n IFN-b
105
IFN-a and IFN-b are secreted and bind to receptors on ________ cells, inducing ?
infected cells
inducing expression of genes whose products enhance cell's susceptibility to CTL-mediated killing
106
IFN-a and IFN-b produced by virus-infected cells can bind to ______ ______ on neighboring ________ cells and activate ?
memb. receptors
uninfected cells
activate JAK-STAT signaling pathways
activation includes expression of gene whose products interfere w/ viral replication
107
pathogen recognition through PRRs is an important bridge between ?
innate and adaptive immunity
by causing activation and maturation of ag-presenting cell APC
108
ag recognition by B cells provides ________ for the activation of _______ .
signal 1
| lymphocytes
109
molecules induced by _______ immune response to microbes provides ______.
innate immunity
provides signal 2
