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Immunology > Innate Immunity (part 1) > Flashcards

Innate Immunity (part 1) Flashcards

1
Q

in most cases, the initial innate immune response to pathogens is

A

prevents, controls, or eliminates infection without an engagement of adaptive immunity

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2
Q

if the impact (pathogen load) is signifiant, innate immunity

1.

2.

A
  1. keeps the infection in check until more specialized adaptive immune responses are activated
  2. directs adaptive immunity towards either Ab-mediated or cell-mediated response
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3
Q

innate immunity eliminates host damaged cells and initiates the process of tissue repair that include:

A
  1. recognition of host molecules related by stressed, damaged, and/or dead host cells
  2. phagocytosis and clearance of cell debris
  3. stimulation and control of tissue remodeling
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4
Q

physical barriers of innate immunity

A

epithelial layers of skin and mocosal/glandular tissues

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5
Q

chemical barriers of innate immunity

A

acidic pH of skin (5.5) and anti-microbial proteins and peptides

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6
Q

if intracellular pathogen is present, what innate immune cell takes action

A

NK cell will kill cell –> releasing pathogens –> that are picked up by phagocytes

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7
Q

activated innate immune cells (e.g. macrophages) produce

A
  1. antimicrobial substances (peptides, interferons)
  2. cytokines and chemokines –> systemic effects (fever); inflammation (recruitment of other cells); and activation of adaptive immune responses
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8
Q

if pathogens overwhelm macrophages, what becomes active

A

dendritic cells which can then activate adaptive immune responses

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9
Q

opsonization

A

process by which the pathogen is marked for elimination

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10
Q

neutrophils

A

polymorphonuclear leukocytes (PMNs)

most abundant of circulating white blood cells

early phagocytosis and killing of microbes

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11
Q

natural killer (NK) cells

A

lysis of infected cells, activation of macrophages

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12
Q

TNF, IL-1, chemokines

A

inflammation

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13
Q

IFN-alpha-beta

A

resistance to viral infection

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14
Q

IFN-gamma

A

macrophages activation

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15
Q

IL-12

A

IFN-gamma production by NK cells and T cells

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16
Q

IL-15

A

proliferation of NK cells

Proliferation of T cells

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17
Q

IL-10, TFT-beta

A

control on inflammation

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18
Q

innate immunity have the ability to discriminate between _____ and _____

A

self

nonself

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19
Q

innate immunity discriminate between self and nonself by the mechanism involving _______ and their receptors called ______

A

pathogen-associated molecular patterns (PAMPs)

Pattern Recognition Receptors (PRRs)

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20
Q

PAMPs (pathogen-associated molecular patterns) have no structural similarity with

A

self Ags

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21
Q

general properties of PRRs (pattern recognition receptors)

A

recognize broad classes of pathogens

are encoded in germline (limited diversity)

can discriminate between self and nonself

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22
Q

mannose-tailed glycans are essential surface molecules of

A

bacteria and viruses

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23
Q

types of PRRs

A

mannose receptors

N-formyl methionyl receptor

toll-like receptor

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24
Q

general properties of PRRs (pattern recognition receptors)

specificity

receptors

distribution of receptors

discrimination of self and nonself

A

specificity: for structures shared by classes of microbes (‘molecular patterns’)
receptors: encoded in germline; limited diversity

distribution of receptors: nonclonal; identical receptors on all cells of the same lineage

discrimination of self and nonself: yes; host cells are not recognized or they may express molecules that prevent innate immune rxns

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25
Q

phagocytes use PRRs to help distinguish

A

self from nonself

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26
Q

PRR-triggered responses of phagocytes:

N-formyl methionyl peptide (fMet) is present in ______ but not in ______

A

prokaryotes

eukaryotes

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27
Q

polymorphonuclear cells (neutrophils) can bind proteins starting with fMet, and use them to control ______ and initiate ______

A

motility

phagocytosis

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28
Q

phagocytosis without activation, results in ______ infection

A

chronic

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29
Q

role of PRRs in phagocytosis

A
  1. microbes bind to phagocyte receptors
  2. phagocyte membrane zips up around microbe
  3. microbe ingested in phagosome
  4. fusion of phagosome with lysosome
  5. killing of microbes by lysosomal enzymes in phagolysosomes and killing by reactive oxidative species and nitric oxide synthase
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30
Q

Pattern Recognition Receptors (PRRs) groups

A

Toll-Like receptors

intracellular NOD-like receptors

scavenger receptors

lectin family of PRRs

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31
Q

some toll-like receptors (TLRs) are present on the cell surface of innate immune cells where they recognize products of ______ while other TLRs are located in endosomes that recognize which respond only to ______

A

extracellular microbes

nucleic acids

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32
Q

toll-like receptors that recognize extracellular pathogens

A

1, 2, 4, 5, 6

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33
Q

toll-like receptors that recognize intracellular pathogens

A

3, 7, 8, 9

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34
Q

toll-like receptor 2 recognizes

A

gram-positive bacteria

peptidoglycan

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35
Q

toll-like receptor 4 recognizes

A

gram-negative bacteria

lipopolysaccaride

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36
Q

toll-like receptors recognize pathogens and actviate

A

inflammation

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37
Q

each pathogen can be recognized by ______ TLRs

A

several

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38
Q

TLR1 : TLR2 heterodimer

ligands:

cells carrying receptors:

cellular location of receptor:

A

ligands: lipopeptides; GPI

cells carrying receptors: monocytes, DC, eosinophils, basophils, mast cells

cellular location of receptor: plasma membrane

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39
Q

TLR2 : TLR6 heterodimer

ligands:

cells carrying receptors:

cellular location of receptor:

A

ligands: lipoteichoic acid; zymosan

cells carrying receptors: monocytes, DC, eosinophils, basophils, mast cells

cellular location of receptor: plasma membrane

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40
Q

TLR3

ligands:

cells carrying receptors:

cellular location of receptor:

A

ligands: double-stranded viral DNA

cells carrying receptors: NK cells

cellular location of receptor: endosomes

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41
Q

TLR4 : TLR4 homodimer

ligands:

cells carrying receptors:

cellular location of receptor:

A

ligands: lipopolysaccharide

cells carrying receptors: macrophages, DC, mast cells, eosinophils

cellular location of receptor: plasma membrane

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42
Q

TLR5

ligands:

cells carrying receptors:

cellular location of receptor:

A

ligands: flagellin

cells carrying receptors: intestinal epithelium

cellular location of receptor: plasma membrane

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43
Q

TLR7

ligands:

cells carrying receptors:

cellular location of receptor:

A

ligands: single-stranded viral RNAs

cells carrying receptors: plasmacytoid DC, NK cells, eosinophils, B cells

cellular location of receptor: endosomes

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44
Q

TLR8

ligands:

cells carrying receptors:

cellular location of receptor:

A

ligands: single-stranded viral RNAs

cells carrying receptors: NK cells

cellular location of receptor: endosomes

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45
Q

TLR9

ligands:

cells carrying receptors:

cellular location of receptor:

A

ligands: unmethylated CpG-rich DNA

cells carrying receptors: plasmacytoid DC, B cells, eosinoophils, basophils

cellular location of receptor: endosomes

46
Q

signaling of extracellular TLRs always results in activation of transcriptional factor

A

NF-kB

nuclear factor - kappa light chain enhancer of B cells

47
Q

what TLR uses TRIF dependent signaling?

what is downstream effect?

A

TLR3

activates NF-kB and Interferon regulatory factors (IRFs)

48
Q

what TLR uses MyD88/TRIF dependent signaling?

what is downstream effect?

A

TLR4

activates NF-kB and Interferon regulatory factors (IRFs)

49
Q

what TLR uses MyD88 dependent signaling?

what is downstream effect?

A

TLRs 1, 2, 5, 6, 7, 8, 9

activates NF-kB and Interferon Regulatory factors

50
Q

broad outcomes of TLR-signaling

A

influence adaptive response

direct antimicrobial response (bacterial death)

tissue injury (host) - apoptosis of host cells; septic shock

51
Q

TLR-dependent signaling pathways activate _______ and _______ which results in transcription of _______

A

NF-kB

IRF

pro-inflammatory genes

52
Q

cytokine IL-12 produced by DCs (after phagocytosis of intracellular pathogen) controls

A

cell-mediated immunity via stimulating T cell response (activates T cells)

53
Q

cytokine IL-12 is not produced by DCs (after phgocytosis of extracellular pathogen), and stimulates the development of

A

humoral adaptive immunity

54
Q

activation of TLRs can also be detrimental to host:

they can contribute to tissue injury by _______

they can lead to life threatening symptoms of ______

A

inducing apoptosis in host cells

septic shock

55
Q

TLR4 signaling pathway in macrophages

A
  1. complex of TLR4, MD2, CD14, and LPS is assembled at the macrophage surface (LBP delivers LPS to cell surface and MD2 and CD14 deliver LPS to TLR4)
  2. MyD88 binds TLR4 –> activates IRAK4 to phosphorylate TRAF6 –> phosphorylation and activation of IKK
  3. IKK phosphorylates IkB/NF-kB complex which leads to IkB degradation –> release of NFkB which then enters the nucleus
  4. NFkB activates transcription of genes for inflammatory cytokines, which are synthesized in the cytoplasm and secreted via the ER
56
Q

nucleotide oligomerization domain (NOD)- like receptors (NLRs) are a specialized group of Pattern Recognition Receptors (PRRs) that recognize ______ proteins

A

intracellular

57
Q

NOD like receptors (NLRs) act as scaffolding proteins that assemble signaling platforms that trigger_______ and _______ signaling pathways.

A

NF-kB

mitogen-activated protein kinase (MAPK)

58
Q

NLRs respond to cytosolic PAMPs and DAMPs by binding other proteins and forming signaling complexes called

A

inflammasomes

59
Q

these pathways control the activation of inflammatory ______

60
Q

by recruitment to the complex, inflammasomes activate

61
Q

main function of caspase-1 is to cleave the inactive cytosolic precursor forms of two homologous cytokines called

A

IL-1b and IL-18

62
Q

secreted forms of proinflammatory cytokines IL-1b and IL-18 drive

A

inflammation

63
Q

inflammasome activation (NLR activation) is induced by a wide variety of cytoplasmic stimuli that are often associated with infections and cell stress, including

A

microbial products (bacterial products)

environmentally or endogenously derived crystals

reduction in cytosolic potassium concentrations

reactive oxygen species

64
Q

NLRP3 senses many DAMPs and PAMPs, including

A

uric acid crystals, aluminum hydroxide crystals used in vaccines, ATP released from mitochondria, silica, bacterial products, bacterial DNA-RNA hybrids, and the influenza virus

65
Q

prolonged activation of NLRP3 inflammasome also causes _______ of macrophages and DCs called pyroptosis which releases inflammatory mediators including: IL-1b, IL-18, TNF, IL-6, and IL-8

A

programmed cell death

66
Q

scavenger receptors are important in tissue remodeling after collateral damage due to

A

inflammation and infections

67
Q

3 types of scavenger receptor (SR) family

A

Class A type I

Class A type II

MARCO (macrophage receptor with collagenous structure)

(are organized as trimeric complexes)

68
Q

scavenger receptors have 3 distinct extracellular structural domains

A
  1. scavenger receptor cysteine-rich (SRCR) domain
  2. the collagen-domain (responsible for binding of polyanionic ligands)
  3. the alpha-helical coiled-coil domain
69
Q

SR-AI and SR-AII mediate the uptake of _______ into cells which lead to atherosclerosis

A

oxidized lipoproteins

70
Q

all SRs bind various bacterial constituents based on ______ charges on bacterial LPS, lipoteichoic acid, nucleic acids, beta-glucan, and proteins

71
Q

SRs are expressed on on macrophages and mediate ______ of microorganisms via recognition of PAMPs leading to clearance of pathogens

A

recognition/phagocytosis

72
Q

SRs KO mice have an increased susceptibility to ______ with several microbial pathogens

A

infections

73
Q

lectin family of PRRs are receptors for what macromolecule

A

carbohydrates

74
Q

all lectin PRRs contain a conserved carbohydrate recognition domain for recognition of

A

microbial mannose, N-acetylglucosamine, and beta-glucans

75
Q

some lectins are soluble proteins found

A

in the blood and ECF

76
Q

some lectins are not soluble and are membrane proteins found on what cells

A

macrophages, DCs, and some tissue cells

77
Q

eukaryotic cell carbohydrates are most often terminated by mannose or galactose and sialic acid

A

galactose and sialic acid

78
Q

lectin receptors facilitate

A

phagocytosis of various microbes

79
Q

activation of lectin receptors triggers the secretion of

A

cytokines that promote inflammation and adaptive immune responses

80
Q

mannose receptor on phagocytes is involved in ______ of microbes

A

phagocytosis

81
Q

soluble mannose-binding lectin (MBL) also known as mannan-binding protein (MBP) is involved in _______ activation via the lectin pathway

A

complement

82
Q

PAMPs and DAMPs trigger

A

inflammation

83
Q

necrosis

A

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

dirty form of cell death characterized by swelling and rupture of cell membrane (cell lyse) which may cause inflammation or harm neighboring cells

84
Q

what generates DAMPs

85
Q

inflammation

A

a response of the innate immunity that involves activation of leukocytes and release of inflammatory mediators

86
Q

inflammation is innate reaction caused by:

  1. an increased blood supply to the affected area resulting in _____ and _____
  2. an increased capillary permeabilty resulting in leaking from the blood vessels, resulting in _____ and ______
  3. a massive influx of ______ into the tissue
  4. an arrival of _______ (16-48 hours)
  5. distortion of the homeostasis and ______ of function
A
  1. redness and heat
  2. swelling and pain
  3. neutrophils
  4. monocytes/macrophages
  5. loss
87
Q

T/F

DAMPS act through same receptors and PAMPs

88
Q

DAMPs activate

89
Q

necrotic cells release what DAMPs

A

HMGB1: activates NF-kB pathway; RAGE is receptor for HMGB1

Uric acid: activates NF-kB pathway

HSP (heat shock proteins): activate NF-kB pathway and release of inflammatory cytokines (TNF-alpha and IL-1beta)

90
Q

epithelia at the portals of entry of microbes provide physical barriers, kill microbes by producing _______ , and harbor intraepithelial ______ that kill microbes and infected cells

A

antibiotics (defensins and cathelicidins)

lymphocytes

91
Q

the rapid movement of intestinal contents through peristalsis, secretion of mucus by _______ cells, and release of extensive antimicrobial products into the lumen by _______ cells all function to limit the invasion of pathogenic organisms

A

goblet

paneth

92
Q

defensins (antimicrobial peptides) are small cationic peptides that contain both _____ and _____ regions

A

cationic

hydrophobic

93
Q

defensins are produced by ______ cells of mucosal surfaces and by granule-containing leukocytes including ______

A

epithelial

neutrophils, NKcells, and CTLs

94
Q

synthesis of defensins are stimulated by ______ and microbial products via ______

A

cytokines (cytokine receptors)

PRRs

95
Q

defensins have direct toxicity to microbes, including:

A

bacteria, fungi, and enveloped viruses

96
Q

defensins kill microbes by

A

inserting into and disrupting functions of the microbial membranes

97
Q

cathe’licidins (antimicrobial peptides) are produced by ______ and barrier ______ cells in the skin, gastrointestinal tract, and respiratory tract

A

neutrophils

epithelial

98
Q

synthesis of cathe’licidins may be stimulated by _____ and microbial products

99
Q

cathe’licidins have multiple mechanisms, including ______ to microorganisms and the activation of ______

A

direct toxicity (disrupting plasma membrane)

leukocytes

100
Q

some cathe’licidins can bind and neutralize

101
Q

some cathe’licidins play an anti-inflammatory role by binding to DNA and blocking

A

inflammasome activation

102
Q

NK cells recognize ligands on

A

infected cells or stressed cells

103
Q

NK cells eliminate reservoirs of infection and thus release intracellular pathogens for

A

phagocytosis

104
Q

NK cells kills host cells by _____ releasing pathogens for phagocytes

105
Q

NK cells respond to _____ produced by macrophages (with phagocytosed microbes) and secrete _____ that activates the macrophages to kill phagocytized microbes

A

IL-12

IFN-gamma

106
Q

NK cell Activating Receptors (KARs) are called killer cell immunoglobulin (Ig)-like receptors that recognize stress-associated molecules ( _____ and _____ ) on the surface of abnormal host cells

A

MICA and MICB

107
Q

activating receptors of NK cells trigger activation of what kinases?

A

protein tyrosine kinases

108
Q

NK cell Inhibitory Receptors (KIRs) recognize _____ and activate protein tyrosine phosphatases (PTP) and inhibit an activation signal

A

class I MHC

109
Q

if insufficient KIR-MHC I binding occurs, the NK cell will proceed to

A

kill the target host cell

110
Q

sufficient binding by KIRs will override the KAR kill signal and

A

spare the life of the host cell

111
Q

how do NK cells kill enemy cells

A
  1. NK cell releases perforins, which polymerize and form a hole in the enemy cell membrane
  2. Granzymes from NK cell enter perforin hole and degrade enemy cell enzymes
  3. enemy cell dies by apoptosis
  4. macrophage engulfs and digests dying cell

Immunology (23 decks)

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