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induced innate immunity (exam 2) Flashcards

1
Q

induced innate immunity

A

4hrs to 4 days after infection
new DNA transcription and protein synthesis

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2
Q

induced innate immunity involves the

A

recruitment of soluble effector molecules and effector cells to infected tissue

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3
Q

what is involved in the induced innate immune response?

A

resident effector cells
internal signaling
external signaling
recruited effector cells
induced complement pathways

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4
Q

internal signaling in induced leads to

A

gene expression changes

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5
Q

external signaling in induced leads to

A

cytokine production

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6
Q

PAMP

A

pathogen associated molecular pattern

structural feature on microbe surface

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7
Q

PRR

A

pattern recognition receptor

molecule on immune cell surface that recognizes and binds PAMPS
distinguish between self, non self and altered self

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8
Q

many microbial ligands are

A

carbohydrates and lipids not present on eukaryotic cells

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9
Q

receptors for microbial ligands

A

lectins
scavenger receptor
CR3, CR4

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10
Q

lectins

A

recognize carbohydrates

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11
Q

scavenger receptor

A

binds negatively charged ligands
including apoptotic human cells

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12
Q

CR3 and CR4

A

bind complement and microbial agents

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13
Q

binding of CR3 and CR4 triggers

A

receptor mediated endocytosis

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14
Q

other macrophage receptors

A

trigger cytokine release

Toll-like receptor, NOD-like receptor, RLR

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15
Q

Toll like receptor

A

several types, each specific for common elements of different microbial products

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16
Q

TLR4

A

recognizes LPS and other molecules on gram NEGATIVE bacteria
generates intracellular signals through cytoplasmic domain –> causes gene expression

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17
Q

TLR4 causes gene expression that triggers

A

induced innate immune responses and inflammation (inflammatory cytokines)

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18
Q

2 major types of Toll like receptors

A
  1. plasma membrane bound
  2. endosomal membrane bound
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19
Q

plasma membrane bound TLR

A

direct contact with EXTRACELLULAR pathogen

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20
Q

endosomal membrane bound TLR

A

sense mostly viral DNA and RNA (INTRACELLULAR)
released in extracellular environment and taken up by cells

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21
Q

When discussing TLR receptors, if there is an intracellular pathogen versus an extracellular pathogen you can expect

A

a different response since different receptors are triggered

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22
Q

NF-kB pathway

A

major role in innate and adaptive response

activation of nuclear factor kB –> antigen binding –> activation and nuclear translocation of NFkB into nucleus –> activates expression of genes –> inflammation

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23
Q

NEMO deficiency

A

genetic lack of IKK subunit
susceptible to bacterial infections

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24
Q

interferon pathway

A

response to viral infections, intracellular bacteria
IRF7/IRF3

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25
IRF7 or IRF3 results in
synthesis and secretion of type 1 interferons --> infected cells will be killed
26
with TLR signaling, cells of the innate immune response can _____________ to different typers of _________
tailor response pathogens
27
TLR response to extracellular bacteria
inflammatory cytokines
28
TLR response to viral
interferons
29
NOD-like receptors
recognize parts of cell wall from phagocytose bacteria production of inflammatory cytokines
30
RIG-1 like receptors
recognize viral RNA production of type 1 interferons
31
cytokines
small signaling proteins made in response to external stimuli
32
pro inflammatory cytokines secreted by MO
IL-1b TNF-a IL-6 IL-12 CXCL8 and CCL2
33
master regulator of inflammation
IL-1b
34
IL-12 induces
NK lymphocyte proliferation
35
chemokines
small proteins that attract specific leukocytes
36
chemokine follow a
concentration gradient (low to high)
37
chemokine recruit
neutrophil and monocytes to alter cell adhesive properties and guide neutrophils/monocytes along gradient
38
IL-1 inhibitors approved for clinical use
anakinra - IL-1 antagonist canakinumab - neutralizes IL-1b rilonacept - neutralizes IL-1a/IL-1b
39
at the site of infection, activated ___________ secrete __________
resident macrophages inflammatory cytokines
40
TNF-a
stimulates vascular endothelial cells to make platelet activating factor triggers bloot clotting
41
systemic infection
pathogen is disseminated throughout the body via bloodstream
42
septic shock
widespread clotting in capillaries, organ failure
43
people with a defective TLR
are at increased risk for septic shock widespread TNF-a production
44
phagocytic cells
macrophages and neutrophils
45
macrophages
long lived reside in tissues immediate response phagocytosis
46
neutrophils
short lived circulate in blood recruited by macrophages
47
neutrophils
granulocytes polymorphonuclear leukocytes short life span, constantly made in bone marrow
48
how many neutrophils enter the mouth and throat each day?
3x10^9
49
_________ of neutrophils is the first step in inflammatory response
arrival
50
neutrophils die within
hours of entry into tissue (this is why pus is at infected wounds)
51
neutrophils have
surface receptors for inflammatory mediators
52
ligand/receptor interactions (for neutrophils) induce
expression of adhesion molecule expression of ligands for adhesion molecules on vascular endothelial cells in capillaries near infection
53
extravasation
migration from vessel to tissue
54
steps of extravasation of neutrophils
1. neutrophil is slowed down by VEC 2. tight binding 3. diapedesis 4. migration to center of infection in tissue
55
tight binding step of extravasation
weak interactions, chemokines induce stronger ones neutrophil stops rolling
56
diapedesis step of extravasation
neutrophil squeezes between adjacent VEC and reaches basement membrane
57
migration to center of infection in tissue (extravasation)
driven by gradient (CXCL8)
58
homing
all WBCs leave the blood and migrate to infected tissue
59
what determines where and when homing occurs?
cytokines and chemokines
60
target identification of neutrophils on pathogens
phagocytic receptors for microbial products complement receptors for opsonized microbes
61
NADPH oxidase
produces superoxide radicals consuming O2 which removes H ions and produces hydrogen peroxide
62
fusion of phagosomes with neutrophil granules
NADPH oxidase raises pH of phagosome activating antimicrobial peptides
63
fusion of phagosome with lysosomes (neutrophils)
acid hydrolases finish the job, then the neutrophil dies
64
chronic granulomatous disease
defect in NADPH oxidase no respiratory burst leads to chronic bacterial/fungal infections
65
neutrophil extracellular traps
trap and kill pathogens
66
systemic effects of inflammatory cytokines in innate immunity
induce fever produce acute-phase response
67
induce fever
act on hypothalamus and muscle fat cells generate heat helps fight infections
68
name of molecules that induce fever
pyrogens
69
acute phase proteins
change spectrum of soluble plasma proteins made by liver cells
70
mannose binding lectin
binds carbohydrates of bacteria, viruses, fungi, protozoans triggers lectin pathway
71
how does mannose binding lectin not attach to human cells?
it can attach only to repetitive structures on pathogens
72
C reactive protein (CRP)
binds phosphocholine of bacterial and fungal cell walls triggers classical pathway in absence of antibody
73
serum amyloid A protein
induces inflammatory cytokine production in macrophages
74
fibrinogen
blood clotting localizes pathogen and prevents spread
75
lectin pathway
binding of MBL to bacterial surface cleaves C4 and C2
76
genetic deficient in MBL
can result in severe meningitis common
77
classical pathway
binding of C1 to C reactive protein on pathogen activates protease cleaves C4 and C2 --> opsonization
78
which pathways of complement need to be induced
lectin and classical
79
the main complement pathway at the start of infection
alternative
80
type 1 interferons
made by any human cell infected with virus interfere with viral replication
81
how do type 1 interferons alert the area that there in an infection?
they signal neighboring cells to prepare alert immune cells make virus infected cells targets for NK cells
82
forms of type 1 interferons
IFN-b and IFN-a
83
synthesis of interferons is induced by
viral infection or binding to a signaling receptor since dsRNA is not found in healthy human cells
84
what type of fashions can interferons act in?
paracrine and autocrine
85
interferon response
induce resistance to viral replication in all cells increase expansion of ligands for receptors on NK cells activate NK cells to kill virus infected cells
86
plasmacytoid dendritic cell
produces huge amounts of type 1 interferon found in blood and lymphoid tissue
87
NK cells
5-25% of lymphocytes against intracellular infections migrate from blood to tissue in response to inflammatory cytokines
88
functions of NK cells
kill infected cells (stimulated by IFN-a,b) produce cytokines (stimulated by IL-12)
89
what type of cytokine does NK cells produce?
IFN-g which activates macrophages
90
NK cells interact with
dendritic cells suppress or activate them depending on sufficiency of innate response
91
how do NK cells kill infected human cells?
inducing them to die via apoptosis
92
ligands on NK cells
inhibitory and activating receptors
93
type of ligands on healthy cells
more inhibitory over activating
94
when NK cells are ________ they outnumber dendritic cells and _______ the dendritic cells
abundant kill
95
when NK cells are scarce, they signal the dendritic cells and
initiate the adaptive immune response

Immunology and Microbiology (22 decks)

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