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Kaplan: Immunology Part 1 > Chapter 4: Periphery: Innate Immune Response > Flashcards

Chapter 4: Periphery: Innate Immune Response Flashcards

1
Q

What does IELs stand for? What is another name for it?

A

Intra-epithelial lymphocytes

γδ T cells

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2
Q

What are receptors of the innate immune system known as?

A

PRRs (pattern recognition receptors)

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3
Q

What do PRRs recognize?

A

PAMPs or DAMPs (damage-associated molecular patterns); released from dying or damaged cells

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4
Q

Where are inflammasomes expressed?

A

in myeloid cells (like macrophages, neutrophils, and dendritic cells)

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5
Q

Activation of inflammasomes results in the production of what inflammatory cytokines?

A

IL-1B and IL-18

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6
Q

What is the purpose of inflammasomes?

A

to activate caspase 1 and then cleave pro cytokines to their active forms

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7
Q

What are the extracellular TLRs?

A

TLR -1, 2, 4, 5, 6

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8
Q

Pathogen target of TLR 2?

A

Bacterial peptidoglycan

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9
Q

Pathogen target of TLR- 4?

A

LPS

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10
Q

Pathogen target of TLR-5?

A

flagellin

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11
Q

Which TLRs recognize bacterial lipopeptides?

A

TLR-1, 2, 6

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12
Q

What are the intracellular (endosomal) TLRs?

A

TLR-3, 7, 8, 9

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13
Q

What pathogen does TLR-3 recognize?

A

DS RNA

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14
Q

What pathogen does TLR- 7, 8 recognize?

A

SS RNA

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15
Q

What pathogen does TLR - 9 target?

A

unmethylated CpG oligonucleotides

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16
Q

What are the downstream effects of activation of TLRs?

A

activation of transcription factors (including NF-kB) which results in the transcription of cytokines, adhesion molecules, and enzymes that are antimicrobial

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17
Q

Where are NLRs located? What does it stand for?

A

NOD-like receptors; intracellular (cytosolic)

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18
Q

What are the NLRs?

A

NOD1, NOD2, NLRP-3

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19
Q

NOD1, NOD2 pathogen target?

A

comoponents of bacterial PG

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20
Q

Downstream effects of NOD1, NOD2?

A

signals via NF-kB result in macrophage activation

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21
Q

NLRP-3 pathogen target.

A

microbial products and molecules from damaged or dying cells (ATP, uric acid crystals, reactive oxygen species)

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22
Q

Downstream effects of NLRP-3?

A

Inflammasome

NLRP- 3 (sensor) + adaptor protein links procaspase 1 and activates it to caspase 1; it is the caspase that cleaves the pro-IL-1B to generate IL-1B

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23
Q

RLR stands for what? Where is it located in the cell?

A

RIG-like receptors; cytoplasm

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24
Q

What is the receptor name of RIG-like receptors?

A

RIG-1, MDA-5

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25
Q

What is the pathogen target of RLR?

A

viral RNA

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26
Q

Downstream effects of RLR?

A

interferon production

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27
Q

Classical M1 pathway of macrophage development is activated by what factors?

A

TLRs, IFN-y

28
Q

The alternative pathway of macrophage development is induced by what cytokines?

A

IL-4, IL-13

29
Q

Classical M1 pathway of macrophage development purpose?

A

phagocytosis, initiate inflammatory response

30
Q

Alternative M2 pathway of macrophage development purpose?

A

tissue repair and control of inflammation

31
Q

What is the overall effect if there is a mutation in signaling molecules affecting TLRs?

A

recurrent, severe bacterial infections (pneumonia)

32
Q

What is the overall effect of gain of function mutations in inflammasome?

A
  • gout
  • atherosclerosis
  • type II diabetes
33
Q

What is the effect associated with NOD-2 mutations?

A

IBD

34
Q

What is the mutation associated with IL-12 receptor deficiency and IFN-y receptor deficiency?

A

recurrent infections with intracellular bacteria (mycobacterium)

35
Q

What CD marker is present on monocytes?

A

CD 14

36
Q

What CD marker is present on macrophages?

A

CD 14

37
Q

What CD marker is present on neutrophils?

A

CD 14

38
Q

What cytokine released from macrophages and DCs activates NK cells?

A

IL-12

39
Q

Name the complement anaphylatoxins.

A

C3a
C4a
C5a

40
Q

Which complement is important for opsonization of pathogens?

A

C3b

41
Q

Which complement proteins are responsible for putting holes in membranes of pathogens?

A

C5b - C9 MAC complex (MAC; membrane attack complex)

42
Q

What organism is the MAC mainly good at killing?

A

Neisseria species

43
Q

In addition to being an anaphylotoxin, what is another important function of C5a?

A

as a chemotactic factor

44
Q

What are the 4 steps in the extravasation of phagocytes?

A

Step 1: Rolling
Step 2: Activation by chemo-attractants
Step: 3: Arrest and adhesion
Step 4: Transendothelial migration

45
Q

Omphalitis

A

a swelling and reddening around the stalk of the umbilical cord

46
Q

Name some major chemoattractive molecules.

A

IL-8,
complement split product C5a,
Leukotriene B4,
Formyl methionyl peptides

47
Q

How do reactive nitrogen species play a role in intracellular killing of pathogens?

A

iNOS (inducible nitric oxide synthase) converts arginine to nitric oxide which has potent antimicrobial properties

48
Q

Function of lysozyme?

A

digests bacterial cell walls by cleaving peptidoclycan

49
Q

Defensins function?

A

form channels in bacterial cell membranes

50
Q

What are the major pro-inflammatory cytokines responsible for producing an acute inflammatory response?

A

IL-1, IL-6, TNF-a

51
Q

What is the major response of IL-1, TNF-a, and IL-6 on the liver?

A

acute-phase proteins, such as CRP, mannose-binding protein, and complement components

52
Q

What are the 2 major mechanisms for dealing with infections. (innate immune response)

A

IFN-α/ β and NK cells

53
Q

What is a major function of interferon?

A

acts on target cells to inhibit viral replication, not the virus

54
Q

How does interferon inhibit viral protein synthesis?

A
  1. activation of an RNA endonuclease which digests viral RNA
  2. phosphorylation of protein kinase, which inactivates eIF2, inhibiting viral protein synthesis
55
Q

Interferon-α has what important clinical applications?

A

well-known antiviral activity and has been used in the treatment of hepatitis B and C infections

Cancer therapy: hairy B-cell leukemia, chronic myelogenous leukemia, and Kaposi sarcoma

56
Q

Interferon- β has what important clinical applications? Benefits?

A

MS

Patients enjoy longer periods of remission and reduced severity of relapses

57
Q

Interferon-y has what important clinical applications?

A

being used in the treatment of chronic granulomatous disease (CGD).

58
Q

What is the major function of IFN-y?

A

potent inducer of macrophage activation and a promotor of inflammatory responses

59
Q

MOA IFN-y is used to treat CGD?

A

significantly reverse the CGD patients inability to generate toxic O2 metabolites inside phagocytic cells

60
Q

How can the side effects of IFN-y treatment be mitigated?

A

acetaminophen

61
Q

Another name for the marker CD16 found on NK cells?

A

FcRy

62
Q

What are the 2 categories of receptor employed by NK cells?

A

(KAR) killer activating receptor
(KIR) killer inhibitory receptor

63
Q

Overall explain how KIR and KARs work?

A

if only KARs are engaged, the target cells will be killed;
if both the KIRs and the KARs are ligated the target cell lives

Therefore the inhibitory signals trump the activation signals

64
Q

What is the major KAR expressed by NK cells?

A

NKG2D

65
Q

What are some major ligands that bind to KARs?

A

MIC glycoproteins

66
Q

Where are MIC proteins found? Explain how KARs act once binding to them.

A

stress proteins that are expressed only when cells are infected or undergoing transformation

Upon binding of KAR to MIC, NK cells become cytotoxic, resulting in death of target cell

67
Q

What is the MOA of KIRs?

A

activate protein tyrosine phosphatases which inhibit intracellular signaling and activation by removing tyrosine residues from various signaling molecules

KIRs on NK cell bind to a specialized type of MHC class I ag called HLA-E

Kaplan: Immunology Part 1 (8 decks)

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