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Immunology Exam 1 > L5: Innate Immunity II > Flashcards

L5: Innate Immunity II Flashcards

1
Q

DAMPs

A

damage associated molecular patterns

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2
Q

PAMPs

A

pathogen associated molecular patterns

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3
Q

exogenous ligands - PAMPs

A

nucleic acid - CpG, ds RNA

lipid A

protein PGN

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4
Q

endogenous ligands - DAMPs

A

nucleic acid - ATP

lipid - oxLDL, saturated fats

protein - HSP, HMGB1

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5
Q

necrosis

A

a passive, catabolic cell death in response to external toxic factors

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6
Q

characteristics of necrosis

A

dirty form of cell death
swelling
cell rupture
may cause inflammation and harm neighbor cells

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7
Q

inflammation is an ______ reaction.

A

innate

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8
Q

inflammation is caused by ?

A
  1. increased blood to area
  2. increased capillary permeability
  3. influx of neutrophils
  4. arrival of monocytes/macrophages
  5. distortion of homeostasis/loss of function
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9
Q

characteristics of inflammation

A 
swelling
pain
redness
heat
loss of function
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10
Q

HMGB1

A

high mobility group box 1

a protein passively released during necrosis

RAGE is its receptor

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11
Q

functions of HMGB1

A

activates NF - kB pathway

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12
Q

uric acid is another diffusible ______ signal that activates the ______ pathway.

A

danger signal

NF-kB pathway

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13
Q

HSPs

A

danger signals

induce NF-kB pathway

release inflammatory cytokines

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14
Q

epithelia are _____ barriers, produce _______ substances, and harbor intraepithelial ________.

A

physical
antimicrobial
lymphocytes – kill microbes and infected cells

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15
Q

defensins

A

small cationic peptides

contain both cationic and hydrophobic regions

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16
Q

what produces defensins?

A

epithelial cells of mucosal surfaces

granule-containing WBCs
neutrophils, nk cells, ctls

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17
Q

synthesis of defensins is stimulated by _______ and ______ products via ____.

A

cytokines
microbial products
PRRs

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18
Q

defensins have _____ toxicity to microbes - including ?

A

direct

bacteria, fungi, enveloped viruses

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19
Q

how do defensins kill microbes?

A

inserting into and disrupting functions of microbial membranes

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20
Q

what do defensins regulate?

A

activation of immune cells involved in inflammatory response to microbes

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21
Q

cathe’licidins

A

antimicrobial peptides w/ microbicidal activity and chemotactic activity for immune cells

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22
Q

cathe’licidins are produced by ?

A

neutrophils

barrier epi cells - skin, GI, respiratory tract

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23
Q

cathe’licidins synthesis is stimulated by ?

A

cytokines

microbial products

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24
Q

functions of cathe’licidins

A

direct toxicity to microorganisms

activation of WBCs

bind/neutralize LPS

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25
Q

mechanism for anti-inflammatory role of cathe’licidins

A

bind to DNA

block inflammasome activation

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26
Q

CD

A

stands for ‘cluster of differentiation’

indicates a defined subset of cellular surface receptors that id cell type and stage of differentiation

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27
Q

NK cell lineage

A

from adaptive lineage but are innate immunity cells

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28
Q

what do NK cells recognize?

A

various stressed cells

in absence or presence of abs

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29
Q

NK cell activation

A

triggered by their recognition
triggers:
lysis of cell
produce cytokines/chemokines

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30
Q

NK cells are biased to produce ?

A

IFN-gamma in most conditions

IL-10 in chronic/systemic inflammation

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31
Q

thru biological activities, NK cells participate in ?

A

shaping the secondary immune response

can boost or dampen macrophage and T cell responses

thru secretion of INF-y/IL-10

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32
Q

NK cells respond to _____ produced by macrophages and secrete _____ .

A

IL-12

INF-y

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33
Q

INF-y activates the macrophages to kill _______ microbes and stimulates productions of ____ in the cells.

A

phagocytized microbes

IL-12

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34
Q

NK cell activating receptors are called ?

A

KIRs

killer cell immunoglobulin (IG) - like receptors

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35
Q

Inhibitory receptors of NK cells

A

these receptors recognize MHC I molecules

activate protein tyrosine phosphatases

inhibiting activation signals

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36
Q

due to inhibitory receptors, NK cells do not kill ?

A

class I MHC expressing cells

= healthy cell

these are receptors on NK cells that recognize MHC on target cell

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37
Q

NK cells recognize cellular stress and become activated via activating NKG2D receptors which bind to ______ and ______ ligands .

A

MICA
MICB

on the surface of stressed cells – associated w/ viral infections and malignant transformation

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38
Q

NK cells also sense the ____ of cell surface molecules to determine if the cell is under too much stress>

A

density

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39
Q

steps in killing target cell by NK cells

A
  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
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40
Q

define the complement system

A

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

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41
Q

the complement system may be initiated by 3 distinct pathways

A

classical pathway

alternative pathway

lectin pathway

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42
Q

early step 1 – complement system

A

formation of C3 convertase complexes

which produce C3a and C3b to trigger inflammation and opsonize microbes

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43
Q

early step 2 – complement system

A

formation of C5 convertase complexes

which produce C5a and C5b which perpetuate inflammation and initiate late steps

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44
Q

late steps – complement system

A

formation of memb. attack complexes

which form holes in microbial memb.

45
Q

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.

A

proteolytic cascades

zymogen

protease

46
Q

enzymatic cascades result in ?

A

tremendous amplification of the amount of proteolytic products that are generated

47
Q

byproducts of complement activation

A

perform various effector functions of the complement system

48
Q

the complement system works in ______ w/ other medically important proteolytic cascades.

A

cooperation

ex. coagulation pathway

49
Q

recognition of microbes by any of the three complement pathways results in recruitment and assembly of complement proteins into ?

A

protease complexes

50
Q

C3a fragment

A

stimulates inflammation by acting as a chemoattractant for neutrophils

51
Q

C3b fragment

A

covalently attaches to microbial surface

serves as opsonin to promote phagocytosis of microbe

52
Q

C3 convertase

A

cleaves C3 into a and b fragments

binds c3b fragment to form protease complex = C5 convertase

53
Q

C5 convertase

A

cleaves C5 into c5a and c5b

54
Q

C5a fragment

A

a very potent chemoattractant

also induces changes in permeability of BVs

55
Q

C5b fragment

A

is attached to microbe memb.

initiates formation of complex of C6, C7, C8, C9 complement proteins
–called membrane attach complex MAC

56
Q

multiples MACs cause ?

A

bacterial leak and lysis

57
Q

the alternative pathway of activation is capable of ?

A

autoactivation

because of ‘tickover’ of C3

58
Q

Tickover

A

occurs spontaneously at a rate of 1% of total C3 per hour

generating fragments a and b

59
Q

alternative pathway – C3b

A

capable of binding factor B

which is cleaved into Ba and Bb by active serum protease factor D

60
Q

fragment Bb – alternative pathway

A

associates w/ C3b and C3 convertase = C3bBb

capable of cleaving additional C3’s generating more C3b

61
Q

alternative pathway — successive proteolytic steps is enhanced by ?

A

serum protein properdin

62
Q

serum properdin

A

stabilizes protein-protein interactions during complement system

63
Q

the alternative pathway can also be initiated as an _________ when fixed C3b that is generated via classical or lectin path binds to factor ___.

A

amplification loop

factor B

64
Q

classical pathway is so called because ?

A

was discovered first

65
Q

the classical pathway is ____ mediated .

A

ab

66
Q

classic pathway – C1q

A

a plasma protein

recognizes and binds to ag-ab complexes

binds to Fc portion of ab

67
Q

classic pathway – once C1q binds ?

A

2 associated serine proteases called C1r and C1s

become active

68
Q

C1r activates _____ so that ?

A

C1s

so that it can activate C2 and C4

69
Q

classical pathway C3 convertase

A

complex C4bC2a

70
Q

classical pathway C5 convertase

A

C4bC2aC3b

71
Q

the lectin pathway is triggered by ?

A

plasma protein – mannose binding lectin MBL

has hexametric structure similar to C1q component of classical pathway

72
Q

MBL recognizes ?

A

terminal mannose residues on microbial glycoproteins and glycolipids

73
Q

after MBL binds to microbes?

A

2 zymogens called - MASP1 and MASP2

are activated

74
Q

MASP1 and 2

A

similar functions to C1r/C1s

initiate downstream proteolytic steps
identical to classic path

75
Q

overview classical pathway

A

–requires IgM or IgG and C1

–C4bC2a is C3 convertase

–C4bC2aC3b = C5

76
Q

overview lectin pathway

A

–does not use C1

–when MBP binds to bacteria – MASPs are activated

  • -C4bC2a = C3
  • -C4bC2aC3b = C5
77
Q

overview alternative pathway

A

–C3 undergoes spontaneous hydrolysis

–factors B and D needed

  • -C3bBb = C3
  • -C3bBbC3B = C5
78
Q

MBL = ?

A

MANNOSE BINDING LECTIN

79
Q

MASP = ?

A

MBL-associated serine protease

also called mannose-associated serine protease

80
Q

complement pathway is not activated on the surface of _____ cells because they express?

A

mammalian cells

express regulatory proteins

which inhibit, disassemble, or cleave the convertases

81
Q

DAF blocks ?

A

C2:C4b interaction

82
Q

DAF or CR1 enhance dissociation of ?

A

C4bC2a interaction

83
Q

CR1 and Factor I cleave ?

A

C4b and C3b

84
Q

Factor I prevents ?

A

the assembly of C3 and C5 convertase

85
Q 
DAF = ?
CR1 = ?
FI = ?
A

decay-accelerating factor

complement receptor 1 = serves as cofactor for FI

factor I = C3b/C4b inactivator

the regulatory proteins expressed by mammal cells

86
Q

complement functions

A

recruitment and activation of WBCs

formation of MAC to lysis microbe

C3b phagocytosis

87
Q

soluble complement fragments:
C3a
C4a
C5a

A

3 = mast cell and basophil

4 = neutrophil

5 = monocyte/macrophage

88
Q

some bacteria can survive in phagolysosomes because ?

A

they express catalase

89
Q

after ingestion and formation of a phagolysosome, microbes are killed by ?

A

reactive oxygen and nitrogen species
and
proteolytic enzymes

90
Q

tissue macrophages are activated by microbial products such as ___ and by NK cells via ?

A

LPS (TLR4)

IFN-y (cytokine receptor)

91
Q

tissue macrophage activation leads to activation of ?

A

transcription factors
transcription of genes
synthesis of proteins

92
Q

TNF and IL-1 act locally on _______ and _______ to induce acute inflammation.

A

leukocytes
endothelium

both cytokines also induce expression of IL-6 from WBCs

93
Q

TNF, IL-1, and IL-6 mediate protective systemic effects of inflammation including induction of ?

A

fever
acute-phase protein synthesis by the liver

leukocytosis

94
Q

define leukocytosis

A

increase production of leukocytes by the bone marrow

95
Q

systemic TNF can cause pathologic abnormalities that lead to _____ shock and ?

A

septic shock

decreased cardiac function
thrombosis and capillary leak
metabolic abnormalities due to insulin resistance

96
Q

pentraxin family

A

family of plasma proteins that recognize microbial structures

and participate in innate immunity

97
Q

CRP and SAP are ?

A

C-reactive protein
serum amyloid P

acute phase proteins from the pentraxin family

98
Q

plasma conc. of CRP and SAP are ______ in healthy individuals but can ?

A

very low

can increase up to 1000x during infections

also in response to inflammation

99
Q

increased levels of CRP and SAP are a result of ?

A

increased synthesis by the liver

induced by cytokines IL-6 and IL-1

100
Q

IL-6 and IL-1 are produced by ?

A

phagocytes as part of the innate immune response

101
Q

CRP and SAP recognize ______ and _________, which are found on bacteria and apoptotic cells.

A

phosphorylcholine

phosphatidylethanolamine

102
Q

how can CRP and SAP activate the complement system?

A

by binding C1q
and
initiating the classical path

103
Q

upon viral infection, viral nucleic acids and proteins are recognized by several ?

A

cellular TLRs

104
Q

TLR-mediated signaling activates transcription factors that stimulate the production of ?

A

type I interferons

IFN-a n IFN-b

105
Q

IFN-a and IFN-b are secreted and bind to receptors on ________ cells, inducing ?

A

infected cells

inducing expression of genes whose products enhance cell’s susceptibility to CTL-mediated killing

106
Q

IFN-a and IFN-b produced by virus-infected cells can bind to ______ ______ on neighboring ________ cells and activate ?

A

memb. receptors
uninfected cells

activate JAK-STAT signaling pathways

activation includes expression of gene whose products interfere w/ viral replication

107
Q

pathogen recognition through PRRs is an important bridge between ?

A

innate and adaptive immunity

by causing activation and maturation of ag-presenting cell APC

108
Q

ag recognition by B cells provides ________ for the activation of _______ .

A

signal 1

lymphocytes

109
Q

molecules induced by _______ immune response to microbes provides ______.

A

innate immunity

provides signal 2

Immunology Exam 1 (8 decks)

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