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Exam 5 NYUMC > Innate Defenses > Flashcards

Innate Defenses Flashcards

1
Q

Innate defenses are an arsenal of

A

pre-existing or rapidly synthesized effector and signalling proteins

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2
Q

Innate defense combine physical barriers with molecular effectors

A

epithelial cells and mucous barriers
patrolling immune cells (macrophages, NK cells, dendritic cells)
soluble mediators- complement and defensins
cytokines- IFN A/B, TNF-A, IL-1, IL-6, IL-12

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3
Q

overall process of viral recognition and innate activation

A
  1. viral recognition via receptor 2. signalling to nucleus via adaptors and kinases 3. activation of transcription factors 4. amplified production of antiviral effector proteins (often the first to be transcribed is IFN-A/IFN-B)
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4
Q

PRR’s = receptors

A

these are on the innate cells to detect the foreign viral products

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5
Q

name PRR

A 
TLR
RIG-1-like-receptors
CDR
NOD-like-receptors
C-type lectin-receptors
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6
Q

TLR = (location)

A

endosomes and plasma membrane

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7
Q

RIG-1- like receptors (location)

A

cytoplasm (mitochondria anchored)

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8
Q

CDR (location)

A

cytoplasm

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9
Q

NOD (location)

A

cytoplasm

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10
Q

C-type lectin (location)

A

plasma membrane

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11
Q

PAMPs

A

pathogen-associated molecular patterns

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12
Q

Examples of PAMPs

A 
cytoplasmic DNA 
dsRNA
naked nuclear DNA
viral genome intermediates
glycoproteins or capsid proteins
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13
Q

Toll-like receptors involved in viral detection

A

TLR3-dsRNA
TLF7/8-ssRNA
TLR9- cpG methylated DNA
TLR13- rRNA

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14
Q

when TLR’s sense virus, it creates a signaling cascade that invovles______ and leads to______

A

adaptors and kinases; and leads to transcription of pro-inflammatory cytokines (TNF-A, IL-1, IL-6, IL-12) and type 1 interferons (A and B)

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15
Q

viral dsRNA activation pathway

A
  1. dsRNA binds to TLR3 and comes into cell
  2. binds to OAS which undergoes conformational change and creates 2’-5’linked oligoadenylates
  3. 2’-5’-linked oligoadenylates act as second messages and activate RNaseL
  4. RNase L dimerizes and degrades cellular and viral RNA
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16
Q

viral ds (cytoplasmic) DNA pathway

A
  1. dsDNA binds to CDN
  2. binds to cGAS in cytoplasm
  3. cGAS is activated to form cGAMP (2’-5’)
  4. cGAMP 2’-5’ binds to and activates STING on ER
  5. STING translocates to perinuclear Golgi where it gaines signaling activity and signals for production of pro inflammatory and antiviral proteins
  6. cGAMP 2’-5’ can also go to neighboring cells via cell junctions, bind to a STING, and initiate antiviral activity in those cells
17
Q

Interferons are what?

A

secreted immune peptides

18
Q

Type 1 Interferons

A

IFN alpha and beta
Source: fibroblasts, epithelial cells, macrophages, monocytes, and plasmacytoid dendritic cells
Stimulus: virus, microbial products
**cells that will be in the periphery encountering a lot of pathogens

19
Q

Type 2 Interferons

A

IFN gamma
Source: T cells and NK cells
Stimulus: immune activation

20
Q

Type 3 Interferons

A

IFN lambda
Source: plasmacytoid dendritic cells and epithelial cells
Stimulus: viruses or microbial products

21
Q

General way that interferon signaling works

A

IFN binds to an IFN receptor
receptor will activate kinases (tyk2 and jak1)
kinases will phosphorylate transcription factors STAT1/2 sitting in the cytoplasm
these will go to the nucleus (and may associate with other factors like IRF9) and induce the transcription of ISGs which tend to be for pro-inflammatory and antiviral proteins

22
Q

ISGs have ______actions and viruses are controlled by ________ with regard to ISGs

A

diverse actions
some ISGs may have some specificity
control of the virus is likely by a combination of many ISGs

23
Q

IFN as therapy for…

A

AIDS-related Kaposis sarcoma herpes virus
Hep B
Hep C
non-viral disorders- autoimmune disorders, cancers, osteoporosis

24
Q

IFN bad because

A

flu-like symptoms, neutropenia, and hepatotoxicity

25
Q

Almost every step in the innate response pathway is

A

antagonized by a viral factor and viruses often block multiple levels of a pathway

26
Q

the signaling response to dsRNA and to viral DNA is started via

A

interferon signaling

27
Q

herpes simplex virus us11 blocks

A

OAS

28
Q

herpes simplex virus ICP34.5 activates

A

a phosphatase that removes a phosphate group from eif2a (placed there by PKR in response to virus) to allow for protein synthesis and viral replication

29
Q

disturbances in innate immunity can lead to autoimmunity- example (disease that has symptoms similar to neonatal infections and/or systemic lupus)

A

AGS- because there are inherited mutations in genes that lead to accumulation of self-nucleic acids that cause an IFN 1 response and lead to an attack of the persons own body

30
Q

systemic lupus ( IFN problems)

A

constant IFN-A signaling from plasmacytoid dendritic cells
activates autoreactive B cells to make auto-plasma cells that make autoantibodies
makes autoreactive CD8 and CD4 cells
DNA and RNA containing immune complexes further activate the pDCs continuing the loop

31
Q

HIV IFN problems

A

HIV patients have elevates IFN-alpha levels; correlates with the severity of the disease
May contribute to immunosuppression by directly or indirectly promoting depletion of CD4 cells

32
Q

Defensins

A

cationic, amphipathic effector peptides of the innate immune system with broad antimicrobial activity

33
Q

alpha-defensins

A

neutrophils, epithelial cells of the gut and genitourinary tract

34
Q

beta-defensins

A

constitutively expressed by epithelial cells of skin and mucosal surfaces

35
Q

connection of IFN to the adaptive immune system

A

IFN–> dendritic cell maturation –> improved antigen presentation and initiation of B and T cell responses

Exam 5 NYUMC (13 decks)

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