Lec 04- Innate Immunity (Part 1) Flashcards

1
Q

What is the function of innate immunity?

A
  • Initial host defense response to pathogens that prevents, controls, or eliminates infection
  • Eliminates damaged cells and initiates tissue repair process
  • Controls adaptive responses
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2
Q

Innate immunity may keep the infection in check until _______.

A

more specialized adaptive immune responses are activated

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3
Q

Steps of damaged cell elimination

A

1- RECOGNIZES and responds to host molecules that are stressed, damaged, and dead host cells
2- CLEARS cell debris by phagocytosis
3- STIMULATES and controls tissue remodeling

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4
Q

How does innate immunity control adaptive responses to intracellular vs. extracellular pathogens?

A
  • Provides danger signals&raquo_space; alert adaptive immune system to respond
  • Reacts in distinct ways to different microbes&raquo_space; influences the type of adaptive immune response
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5
Q

Innate Immunity component:

Cellular and chemical barriers

A
  • skin
  • mucosal epithelia
  • antimicrobial molecules
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6
Q

Innate immunity component:

Blood proteins

A
  • complement
  • acute phase proteins
  • cytokines
  • others
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7
Q

Innate immunity component:

Cells

A
  • phagocytes (macrophages/neutrophils)
  • dendritic cells
  • natural killer cells
  • innate lymphoid cells
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8
Q

3 Major Type of Defenses of Innate Immunity

A

-Inflammation
> Leukocytes and plasma proteins

-Physical barriers
> Skin and epithelial cells

-Anti-viral responses
> Inhibition of viral replication

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9
Q

Specificity:

Innate vs. Adaptive

A

Innate:

  • Pathogen-associated molecular patterns (PAMPs)
  • Damage-associatd molecular patterns (DAMPs)

Adaptive:
-Fine structures of microbial and non microbial Ags

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10
Q

Receptors:

Innate vs. Adaptive

A

Innate = Pattern recognition receptors (PRRs)

Adaptive = Greater diversity of BCRs and TCRs generated by somatic recombination

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11
Q

Distribution of receptors:

Innate vs. Adaptive

A

Innate = NONCLONAL (identical receptors on various cells)

Adaptive = CLONAL (identical on a single cell, but different between 2 cells)

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12
Q

Discrimination of self and non-self:

Innate vs. Adaptive

A

Innate = YES

Adaptive = YES

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13
Q

Where are PRRs located?

A
  • extracellularly
  • endosomes
  • cytosol
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14
Q

What are the 5 families of microbial PRRS?

A
1- TLR family (surface and endosomal)
2- CLRs family
3- NOD-like receptors (NLRs) family
4- RIG-like receptors (RLRs) family
5- Cytosolic DNA sensors (CNS) family
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15
Q

PRRs on the cell surface bind PAMPs from __________.

A

extracellular pathogens

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16
Q

What do endosomal TLRs recognize?

A

nucleic acids of phagocytized microbes

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17
Q

Which family of PRRs is an evolutionarily conserved family?

A

TLRs

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18
Q

TLRs can form _______ or ________.

A

homodimers or heterodimers

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19
Q

What do TLRs recognize?

A

Both PAMPs and DAMPs

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20
Q

Which TLRs are expressed on the cell surface?

A
TLRs:
1
2
4
5
6
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21
Q

Which TLRs are expressed in endosomes?

A
TLRs:
3
7
8
9
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22
Q

Which TLRs use the adapter protein MyD88 and activate the transcription factors NF-kB and AP-1?

A
TLRs:
1
2
5
6
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23
Q

Which TLR uses the adaptor protein TRIF and activates the IRF3 and IRF7 transcription factors?

A

TLR3

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24
Q

Which TLR can activate both pathways?

A

TLR4

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25
Q

Which TLRs in the endosome use My D88 and activate both NF-kB and IRF7?

A

TLRs:
7
9

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26
Q

All TLRs signal through MyD88 except _______.

A

TLR3

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27
Q

Which TLRs also engage TIRAP?

A

TLR4 and the TLR2 subfamily (TLR 1,2,6)

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28
Q

Which TLR signals through TRIF?

A

TLR3

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29
Q

What is used in conjunction with TRAM in the TLR4-MyD88 independent pathway?

A

TRIF

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30
Q

TLRs are expressed on ______ cells

A

Immune cells

including macrophages and dendritic cells

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31
Q

Microbial lipoproteins activate mammalian immune cells through ________.

A

TLR2

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32
Q

LPS activates cells via ______.

A

TLR4

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33
Q

Through which TLR do bacterial DNA sequences containing unmethylated cytosine-guanosine dinucleotides (CpGs) work?

A

TLR9

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34
Q

TLR-dependent signaling pathways activate ______ which results in transcription of pro-inflammatory genes.

A

NF-kB

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35
Q

Which cytokine controls the adaptive T cell immune response?

A

IL-12

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36
Q

Activation of TLRs triggers ____.

A

antimicrobial pathways that directly kill the pathogen

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37
Q

What are the 2 ways activation of TLRs can be detrimental to the host?

A
  • can contribute to tissue injury by inducing apoptosis

- can lead to life-threatenting septic shock

38
Q

Where is the secreted from of IL-1b and IL-18 produced?

A

in the inflammasome

39
Q

From which family is the NLRP subfamily?

A

14 NOD-like receptors

40
Q

How do NLRPs respond to cytosolic PAMPs and DAMPs?

A
  • binding other proteins

- forming signaling complexes (inflammasomes)

41
Q

How do inflammasomes activate the enzyme caspase-1?

A

by recruitment to the complex

42
Q

What is caspase-1?

A

a protease with cysteine residue in the active site

43
Q

What is the main function of caspase-1?

A

to cleave the inactive cytoplasmic precursor forms of IL-1b and IL-18

44
Q

What are the secreted forms of IL-1b and IL-18?

A

proinflammatory cytokines

45
Q

What kind of complexes make up the scavenger receptor family?

A

Trimeric complexes of type II transmembrane polypeptides

46
Q

What are the 3 extracellular structural domains of the scavenger receptor family?

A

1- SR cysteine-rich (SRCR) domain
2-The collagen-like domain, which is implicated in the binding of polyanionic ligands
3-The a-helical coiled-coil domain, believed to assist in receptor trimerization

47
Q

What are the 3 domains on the Macrophage mannose receptor (MMR) and DEC-205?

A

1- cyesteine-rich N terminal domain
2- fibronectin-like domain
3- multiple calcium-dependent lectin domains that bind various carbohydrate ligands

48
Q

What do scavenger receptors mediate?

A

the uptake of oxidized lipoproteins into cells

49
Q

Which scavenger receptors are expressed on macrophages and mediate the recognition/phagocytosis of microorganisms?

A

SR-A and CD36

50
Q

CD36 also functions as what?

A
  • a coreceptor in TLR2/6 recognition

- response to bacterially derived lipoteichoic acid and diacylated lipopeptides

51
Q

SRs bind bacterial constituents based on _______ of bacterial LPS, lipoteichoic acid, nucleic acids, b-glucan, and proteins

A

negative charges

52
Q

SRs KO mice have increased _________ with several microbial pathogens

A

increased susceptibility to infection

53
Q

Receptors for carbohydrates belong to the _________ family.

A

C-type lectin family because they bind to carbohydrates

54
Q

All receptors contain a conserved carbohydrate recognition domain for recognition of ______, ______, and ______.

A
  • microbial mannose
  • N-acetylglucosamine
  • b-glucans
55
Q

EUK carbohydrates are most often terminated by _______ and _______.

A

galactose and sialic acid

56
Q

Where are soluble lectins found?

A
  • blood

- extracellular fluids

57
Q

Where are integral membrane protein lectins found?

A
  • surfaces of macrophages
  • dendritic cells
  • some tissue cells
58
Q

Function of receptors for carbohydrates

A
  • facilitate the phagocytosis of microbes

- secretion of cytokines that promoted subsequent adaptive immune responses

59
Q

What do mannose receptors recognize on microbial surfaces?

A
  • terminal D-mannose
  • L-fructose
  • N-acetyl-D-glucosamine sugars
60
Q

The mannose receptor is involved in __________ of microbes.

A

phagocytosis of microbes

61
Q

3 types of epithelial barriers

A
  • physical barrier to infection
  • killing of microbes by locally produced antibiotics
  • killing of microbes and infected cells by intraepithelial lymphocytes
62
Q

What are defensins?

A

-small cationic antimicrobial peptides

63
Q

What do defensins contain?

A
  • cationic regions

- hydrophobic regions

64
Q

What produces defensins?

A
  • epithelial cells of mucosal surfaces

- granule-containing leukocytes (neutrophils, natural killer cells, CTLs)

65
Q

What stimulates defensin synthesis?

A
  • cytokines

- microbial products

66
Q

To what do defensins have direct toxicity?

A

Microbes

including:

  • bacteria
  • fungi
  • enveloped viruses
67
Q

Function of defensins

A

regulate activation of cells involved in inflammatory response to microbes

68
Q

What produces cathelicidins?

A

-neutrophils
-barrier cells in the:
> skin
> GI tract
> respiratory tract

69
Q

What are cathelicidins synthesized as?

Cleaved into?

A

Synthesized as: an 18-kD 2-domain precursor protein

Cleaved into: 2 protective peptides

70
Q

To what do cathelicidins have direct toxicity?

A
  • Microorganisms

- Activation of leukocytes

71
Q

What is LL-37?

A
  • The C-terminal fragment of cathelicidins
  • Can bind and neutralize LPS
  • Binds to DNA blocking AIM2 inflammasome activation
72
Q

Functions of Anti-microbial Peptides (AMP)

A
  • Wound repair
  • Initiation of TLR9 activation
  • Recruitment of T cells
  • Mast cell de-granulation and histamine release&raquo_space; vasodilation
  • Recruitment of immature dendritic cells
  • Promotion of angiogenesis
  • Anti-endotoxin activity
  • Killing microbes
73
Q

Where do innate lymphoid cells (ILCs) develop?

A

from common bone marrow precursor

74
Q

The common bone marrow precursor is identified by ______.

A

the Id2 transcription factor

75
Q

What are the 3 subsets of Id2?

A

T-bet (ILC1)
GATA-3 (ILC2)
RORyt (ILC3)

76
Q

How are the 3 subsets of Id2 distinguished?

A

by expression of distinct transcription factors and cytokines produced

77
Q

Which cytokines does ILC1 produce?

A

IL-2
IL-18

Defense against viruses

78
Q

Which cytokines does ILC2 produce?

A

IL-25
IL-33

Allergic inflammation

79
Q

Which cytokines does ILC3 produce?

A

IL-1
IL-23

Intestinal barrier function
Lymphoid organogenesis

80
Q

Functions of natural killer cells

A
  • RECOGNIZE ligands on infected cells or stressed cells
  • KILL infected or stressed host cells
  • ELIMINATE reservoirs of infection
  • RELEASE intracellular pathogens for phagocytosis
81
Q

What do natural killer cells respond to and secrete?

A

Respond to: IL-12 produced by macrophages

Secrete: IFN-y

82
Q

Function of IFN-y

A

activates macrophages to kill phagocytized microbes

83
Q

What are Killer cell immunoglobulin (Ig) like receptors (KIRs)?

A

NK-cell activating receptors

84
Q

Function of Killer cell immunoglobulin (Ig) like receptors (KIRs)?

A
  • recognize ligands on target cells

- activate protein tyrosine kinases (PTKs)

85
Q

What inhibits activation signal of natural killer cells?

A

The inhibitory receptors that:

  • Recognize class I MHC molecules
  • Activate protein tyrosine phosphatases (PTPs)
86
Q

Do NK cells kill class I MHC-expressing healthy cells?

A

NO!

87
Q

MHC

A

major histocompatability complex

88
Q

Any inhibition of class I MHC expression on infected cells leads to what?

A
  • NK cell inhibitory receptor not engaged

- The activating receptor functions unopposed to trigger activation of NK cells

89
Q

KARs

A

Killer Activation Receptors

90
Q

NCR

A

Natural Cytotoxicity Receptors

-(with stimulation) mediate NK killing and release of IFN-y