Innate Immunity Part I Flashcards

1
Q

How do B and T cells migrate to different zones of the LN?

A

By chemokines that are produced in specific areas.

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2
Q

How do Ag-loaded DCs enter the lymph node?

A

Though afferent lymphatic vessels that come from sites of Ag entry.

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3
Q

Once DCs are in the lymph node, what regions of the lymph node do they migrate to?

A

T-cell rich areas of the node.

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4
Q

How do naive T lymphocytes home to lymph nodes?

A

Via L-selectin binding to peripheral lymph node addressin on the HEV.

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5
Q

Are HEVs present in primary or secondary lymphoid organs?

A

Secondary.

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6
Q

Which chemokines are displayed on the surface of the HEV?

A

Chemokines CCL19 and CCL21

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7
Q

What must chemokines bind to in order to activate integrins?

A

CCR7

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8
Q

What receptor is necessary for effector T cells to exit the LN?

A

S1PR1. Effector T cells sense a gradient that the receptor produces, which allows them to leave the lymph node.

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9
Q

If an S1P gradient is produced in lymph nodes, what type of T cell will respond to it (and subsequently leave the LN)?

A

Effector T cells.

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10
Q

How do Ag-activated T cells respond to S1P?

A

They do not respond to it, and hence stay in the lymph node.

Ag-activated T cells have low levels of S1PR1 and cannot exit the lymph node.

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11
Q

Activated effector T cells home to sites of infection in peripheral tissues. Cell migration into tissue is mediated by what substances?

A

E-selectin, P-selectin, integrins and chemokine (CXCL10) that are produced at sites of infection.

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12
Q

Many chemokines and chemokine receptors are involved in what process?

A

They are involved in effector/memory T cell migration.

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13
Q

What ligand on the endothelial cell does L-selectin bind to?

A

PNAd

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14
Q

What is the function of L-selectin/PNAd?

A

Initial weak adhesion of naitve T cells to the HEV in the lymph node.

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15
Q

What ligand on the endothelial cell does CCR7 bind to?

A

CCL19 or CCL21

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16
Q

What is the function of CCR7/CCL19 & CCL21?

A

Activation of integrins and chemokinessis

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17
Q

What is the function of LFA-1/ICAM-1?

A

Stable arrest of cells on HEV in the LN.

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18
Q

What do E and P selectin ligands bind do on endothelial cells?

A

E or P selectin

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19
Q

What is the function of E/P selectin ligands and E/P selectins?

A

Initial weak adhesion of effector and memory T cells to cytokine activated endothelium at peripheral site of infection.

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20
Q

What is the function of CXCR3/CXCL10?

A

Activation of integrins and chemokinesis

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21
Q

What is the function of CCR5/CCL4?

A

Activation of integrins and chemokinesis

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22
Q

What is the function of LFA-1 or VLA-4/I-CAM1 or VCAM-1?

A

Stable arrest of cytokine-activated endothelium at peripheral sites of infection.

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23
Q

What are the three bonds made during jrolling and arrest of an effector T lymphocyte on endothelial cells?

A

PSGL-1 & Psel/Esel

CD44 & CD 44

VLA-4 & VCAM

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24
Q

What receptor is important for the mobilization of effector T cells in sites of infection and inflammation?

A

CD44

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25
Q

What do endothelial cells secrete that facilitate the homing mechanism of effector T lymphocytes?

A

Chemokines

E & P selectin

Hyaluronic acid

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26
Q

What must vascular endothelial cells express in order for CD44 to mediate rolling interactions?

A

Hyaluronic acid

Natural ligans

E-selectin

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27
Q

Chemokine signaling via ____ results in increased integrin affinity, such as VLA-4, which enhances adhesiveness.

A

GPCRs (G protein coupled receptors)

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28
Q

True or false: naive B cells use the same basic mechanisms as do naive T cells to home to secondary lymphoid tissues throughout the body.

A

True

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29
Q

What is the migration pathway of immature B cells?

A

Bone marrow -> blood -> red pulp of spleen -> white pulp of spleen.

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30
Q

As B lymphocytes mature, what receptor do they express that promotes their movement into the white pulp?

A

Chemokine receptor CXCR5.

The migration occurs in response to chemokine CXCL13.

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31
Q

Once maturation of B cells is completed within the white pulp, where do they migrate to?

A

They reenter circulation and home to lymph nodes and mucosal lymphoid tissues.

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32
Q

What does homing of mature naive B cells from the blood into LNs involve?

A

Rolling interactionf of HEVs, chemokine activation of integrins, and stable arrest.

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33
Q

Homing of mature naive B cells from the blood into LNs involves what chemokines?

A

CXCL12 and CCL19/CCL21 on HEV, as well as their chemokine receptors CXCR4 and CCR7 on naive B cells.

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34
Q

In the stroma, B cells migrate into follices driven by what receptor?

A

CXCL13.

It is recognized by CXCR5 expressed on naive B cells.

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35
Q

What is a process that may occur when B cells enter a follicel?

A

They may encounter Ag and become activated.

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36
Q

What are the cirulating effector cells involved in innate immunity?

A

Neutrophils, macrophages and NK cells

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37
Q

What are the circulating effector proteins involved in innate immunity?

A

Complement

Mannose-binding protein lectin

C-reactive protein

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38
Q

What is the function of complement?

A

It kills and opsonizes microbes.

It also activates leukocytes.

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39
Q

What is a common function of mannose-binding lectin and C-reactive protein?

A

Both activate complement.

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40
Q

What is opsonization?

A

The process by with a pathogen is marked for elimination.

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41
Q

Which cytokine in innate immunity causese inflammation?

A

TNF, IL-1 cytokines

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42
Q

Which cytokine from innate immuity shows resistance to viral infection?

A

IFN-alpha, beta

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43
Q

What cytokine from innate immunity activates macrophages?

A

IFN-gamma

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44
Q

What cytokine from innate immunity faciliates IFN-gamma production by NK cells and T cells?

A

IL-12

45
Q

Which cytokine from innate immunity causese the proliferation of NK cells?

A

IL-15

46
Q

Which cytokine from innate immunity causes control of inflammation?

A

IL-10, TGF-beta

47
Q

What are three functions of innate immunity?

A

It is the initial host defense response to pathogens

It eliminates damaged cells and initiates tissue repair

It controls adaptive responses to intracellular vs. extracellular pathogens.

48
Q

True or false: innate immunity has the ability to discriminate between self and nonself.

A

True

49
Q

The basic mechaism of discriminating between self and nonself involves receptors which recognize what?

A

Pathogen associated molecular patterns (PAMPs)

50
Q

What is the erm for cell receptors that recognize PAMPs?

A

Pattern recognition receptors (PRRs).

51
Q

What is a general property of PRRs on the surface of bacteria and viruses?

A

They have mannose-tailed glycans.

52
Q

What does it mean when a PRR is germ-line encoded?

A

It refers to sequences that are found in gamete producing cells.

53
Q

Why do phagocytes use PRR-triggered responses?

A

To help distinguish self from non-self.

54
Q

True or false: N-formylmetionyl peptide (fMet) is present in prokaryotes, but not eukaryotes

A

True

55
Q

What do polymorphonuclear cells use fMet for?

A

The initiation of phagocytosis.

56
Q

What are two functions of PRRs?

A

They trigger phagocytosis and kill microbes.

57
Q

What is iNOS?

A

Inducible nitric-oxide synthase.

58
Q

What are toll like receptors (TLR)?

A

Receptors that recognize extracellular pathogens.

They recognize products of extracellular microbes.

59
Q

What do endosomal TLRs only respond to?

A

Nucleic acids

60
Q

TLRs recognize ____ and activate ____

A

TLRs recognize pathogens and activate inflammation.

61
Q

What is the outcome of signaling of extracellular TLRs?

A

Pro-inflammatory cytokine secretion.

62
Q

TLRs 1, 2, 5 and 6 use the adaptor protein ____ and activate the transcription factors, NF-KB

A

MyD88

63
Q

TLR3 usese the adaptor protein ___ and activates the IRF transcription factors

A

TRIF

64
Q

TLR4 can activate what signaling pathways of TLRs?

A

Both pathways

65
Q

What do TLRs 7 and 9 activate?

A

NF-KB and IRF

66
Q

TLRs are important for what type of immune response?

A

Innate immune response

67
Q

TLRs are expressed on immune cells. What specific immune cells are they expressed on?

A

Monocytes, neutrophiles, macrophages and dendritic ells.

68
Q

TLR-dependent signaling pathways activate NF-KB. What is the function of NF-KB?

A

It results in the transcripton of pro-inflammatory genes.

69
Q

Which cytokine controls the adaptive T-cell immune response?

A

Cytokine IL-12

70
Q

What does the activation of TLRs result in?

A

The activation of antimicrobial pathways that directly kill a pathogen.

71
Q

Activation of TLRs can be detrimental to the host. What can they specifically do?

A

Contribute to tissue injury by inducing apoptosis

Can lead to symptoms of septic shock.

72
Q

TLR4 eventually leads to the transcrption of genes for what substance?

A

Inflammatory cytokines.

They are synthesized in the cytoplasm and secreted in the ER.

73
Q

What are some inducers of innate immunity?

A

PAMPs

Nucleic acid

Lipid A

Protein PGN

74
Q

What are some sensors of innate immunity?

A

Toll-like receptors

NOD-like receptors

C-type lectin

75
Q

What are some mediators of innate immunity?

A

TNF alpha

IL-6

IL-1 beta

76
Q

What do PAMPs and DAMPs (damage associated molecular patterns) trigger?

A

Inflammation

77
Q

What does necrosis generate?

A

DAMPs

78
Q

Why is necrosis detrimental to other cells?

A

Necrosis involves swelling and rupture of the cell membrane. This may cause inflammation or harm other neighboring cells.

79
Q

What is inflammation?

A

An innate reaction caused by:

An increased blood supply to the affected area

Increases capillary permeability

Massive influx of neutrophils

Arrival of macrophages

Distortion of homeostasis and loss of function

80
Q

What are some physiological consequences of inflammation?

A

Heat

Redness

Swelling

Pain

Loss of function

81
Q

What do DAMPs activate?

A

NF-KB

82
Q

What protein activates the NF-KB pathway?

A

HMGB1 (high mobility group box 1). It is a protein passively released during necrosis.

Uric acid and HSPs also activate the NF-KB pathway.

HSP induces the release of inflammatory cytokines.

83
Q

What are nucleotide oligomerization domain-like receptors?

A

A specialized group of intracellular proteins.

84
Q

What is the function of NOD-like receptors (NLRs)?

A

They play a critical role in the regulation of the host innate immune response.

They also act as scaffolding proteins that assemble signaling platforms that trigger NF-KB and MAPK signaling pathways.

85
Q

What do NLRs control?

A

The activation of inflammatory responses.

86
Q

How do NLRs respond to PAMPs and DAMPs?

A

By binding other proteins and forming signaling complexes called inflammasome.

87
Q

What do inflammasomes activate?

A

Caspase-1

88
Q

What is the main function of caspase-1?

A

To cleave the inactive cytoplasmic precursor forms of two homologous cytokines (IL-1beta and IL-18).

89
Q

What process occurs from secreted forms of proinflammatory cytokines IL-1 beta and IL-18?

A

Inflammation.

90
Q

Where are sereted forms of IL-1beta and IL-18 produced?

A

In the inflammasome

91
Q

What three receptors are part of the scavenger receptor family?

A

SR class A type 1 (SR-A 1)

SR class A type 2 (SR-A II)

MARCO

92
Q

What is the function of SRs? (Scavenger receptors)

A

They mediate the uptake of oxidized lipoproteins into cells.

They are expressed on macrophages and mediate recognition/phagocytosis of microorganisms.

They also bind various bacterial constituents based on negative charges of bacterials LPs.

93
Q

Receptors for carbohydrates blong to what family?

A

C-type lectin family.

They contain a conserved carbohydrate recognition domatin for recognition of microbial mannose, N-acetylglucossamine and B glucans.

94
Q

Most eukaroytic cell carbohydrates are most often terminated by what acids?

A

Galactose and sialic acid

95
Q

What are functions of leptin receptors?

A

They facilitate the phagocytosis of microbes.

They also trigger secretion of cytokines that promote adaptive immune responses.

96
Q

Mannose receptors on phagocytes are involved in what process?

A

The phagocytosis of microbes.

97
Q

What is soluble mannose-binding lectin?

A

It is a protein that is involved in complement activation via the lectin pathway.

98
Q

What is the importance of epithelium in innate immunity?

A

They provide physical barriers, produce antimicrobial substances, and harbor intraepithelial lymphocytes that are believed to kill microbes and infected cells.

99
Q

What are defensins?

A

Small cationic peptides that contain both cationic and hydrophobic regions.

100
Q

What are defensins produced by?

A

Epithelial cells of mucosal surfaces and by granule-containg leukocytes (neutrophils, NK cells and CTLs)

101
Q

What is the synthesis of denfensis stimulated by?

A

Cytokines and microbial plroducts.

102
Q

What happens when defensins are exposed to microbes?

A

The microbes will die, since defensins are toxic to them.

The affected microbes include bacteria, fungi and enveloped viruses.

103
Q

How do defensins kill microbes?

A

By inserting into and disrupting functions of the microbial membranes.

104
Q

What is a function of defensins?

A

They regulate activation of immune cells involved in the inflammatory response to microbes.

105
Q

What are cathelicidins?

A

They are antimicrobial peptides. They also activate leukocytes and can bind and neutralize LPs.

They also plan an anti-inflammatory role by binding to DNA and blocking inflammasome activation.

106
Q

What molecules releases anti-microbial peptides? (AMPs)?

A

Phagocytes

107
Q

AMPs recruit T cells, neutralize inflammatory cytokines, and recruit immature dendritic cells.

A

Interesting.

108
Q

How do naive lymphocytes enter the lymph node?

A

Through an artery.

They leave the circulation by moving across the wall of the HEV.