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IMIN 200 > Magor- Topic 7: Immune defenses against viruses > Flashcards

Magor- Topic 7: Immune defenses against viruses Flashcards

1
Q

Innate immunity can mean difference between life & death. Because

A

Because the adaptive immune system takes 3 days to get up and running & that’s so much time & during that time, it determines whether you live or die from a viral infection.

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2
Q

Advantage of adaptive immune response

A

You have a memory of that infection

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3
Q

When does the adaptive immune system & recovery begin?

A

If it gets through a round of replication, there’s usually some symptoms & disease associated and then it will be the beginning of adaptive immune system & recovery.

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4
Q

Very early, the production of _______ and _______ are critically important in the immune response

A

interferons (IFN) and cytokines

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5
Q

You need a lot of interferons in innate immune response. But what happens if you get a lot of cytokines?

A

That’s a bad thing

Viruses have lots of ways of turning down interferon & turning on pro-inflammatory cytokines, which doe snot have a good outcome.

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6
Q

Virus titre decreases as

A

As the cytotoxic T cells arise

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7
Q

These two are tissue residents. So they are the first cells to see the viral infection in innate immune response

A

Macrophages and Dendritic cell

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8
Q

These cells are the early responders in innate immunity

A

Natural killer cell

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9
Q

Main antiviral players in adaptive immunity

A

B cell (make antibodies)
T cell ( make cytotoxic T cells)

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10
Q

_______ will become some of those first responders in innate immune response. They are 70% of our WBCs & they come in quickly post-infection.

A

Neutrophil

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11
Q

Innate defenses are most important in _____ infection

A

acute

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12
Q

Pattern recognition: Antigens are recognized by _____________

A

innate immune system
- this is gene encoded

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13
Q

Innate immune system is responsible for recognizing that something poses _________

A

danger

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14
Q

Antiviral pattern recognition receptors are _________ or ________

A

endosomal or cytoplasmic

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15
Q

Three toll receptors that are important in viral infections

these are the endosome receptors

A

TLR3, TLR7, TLR9

They’re the ones that actually detect pathogens in the endosome.
Because many viruses come in through that receptor mediated endocytosis, they are in the endosome.

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16
Q

What does TLR3 detect?

A

dsRNa

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17
Q

What does TLR7/8 detect?

A

ssRNA

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18
Q

What does the TLR9 detect?

A

unmethylated CpG DNA

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19
Q

What is the final step after the detection of TLR3,7,9?

A

It is turning on pro-inflammatory cytokines in the help of IL-6 and INF

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20
Q

Two important cytoplasmic receptors
These two detect RNA
Any virus that is making RNA in the cytoplasm is going to get detected by these receptors.

A

MD5 and RIG1

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21
Q

MDA5

A
  • cytoplasmic receptor
  • detects long dsDNA
  • particularly detects Vpg on the genome & signals through, turns on IFN & pro-inflammatory cytokines
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22
Q

RIG1 is a cytoplasmic receptor that detects _______

A

short dsDNA (esp. hairpins)

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23
Q

cGAS

A
  • cytoplasmic receptor that detects DNA
  • works through sting to turn on IFN
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24
Q

Neutrophils

A
  • filled with granules that dump out defensins that are antiviral
  • phagocytic
  • first to arrive at sites of infection
  • The neutrophils come in in response to signals sent out by dendritic cells & macrophages
  • About 70% of the circulating leukocytes are neutrophils
  • Granules contain antimicrobial peptides including defensins
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25
Q

Macrophages release cytokines that act locally (recruit more leukocytes) and systematically (many effects)
What are three pro-inflammatory cytokines?

A

IL-1
IL-6
TNF-alpha

26
Q

Systemic effects of pro-inflammatory cytokines

A
  • cause fever
  • cause you to go to sleep
  • make you feel tired
  • pro-inflammatory cytokines act on hypothalamus
  • colony stimulating factors act on bone marrow to increase WBC output

It’s always not a good idea to take drugs to make fever go down, even though you feel like crap, it is serving purpose

27
Q

the most potent antiviral thing known & it is the thing that makes you feel like crap when you’re sick.

A

Interferon (IFN)

28
Q

Acute phase proteins

A
  • are made by the liver 100-1000 fold upregulation
  • called acute phase proteins because during the acute phase of an infection, they’re elevated sometimes.
29
Q

Proinflammatory cytokines induce liver to produce ___________

A

acute phase reactants -effector proteins made in response to infection.
-often bind directly to virus
-act as opsonins facilitating phagocytosis

30
Q

C-reactive protein

A

can be used as a diagnostic for infection

31
Q

Mannan-binding lectin (MBL)

A
  • binds to mannose on viral glycoproteins and acts as an opsonin facilitating phagocytosis
  • can also activate complement via the lectin pathway
32
Q

αGal

A
  • on many viruses that are made in non-primate hosts
  • sugar that’s on the surface of glycoproteins
  • we don’t make αGal because there’s been a mutation in the enzyme
  • all other non-primate animals make αGal
  • main line of defense against animal viruses is due to antibodies against αGal and complement activation
33
Q

What is one of the reason why you don’t really have to worry about getting a virus form a cat or dog?

A

You make an immune response to this αGal

34
Q

What are the the Type I interferons

A

IFN-α and IFN-β

35
Q

This is a Type II interferon

A

IFN-γ

36
Q

IFN-α

A
  • produced by: leukocytes (WBCs)
  • turned on by: virus infection, dsRNA
37
Q

IFN-β

A
  • produced by: fibroblasts, epithelial cells
  • turned on by: virus infection, dsRNA
  • made by all cells
38
Q

IFN-γ

A
  • produced by: T cells, NK cells
  • turned on by: antigens, mitogens, IL-2, IL-12
39
Q

Mitogens

A

non-specific stimulators of lymphocytes

40
Q

The innate immune response is amplified by

A

cooperation in the immune system

Activated macrophages -> make TNF-alpha
TNF-alpha -> activate NK cells
NK cells -> activate IFN-γ
IFN-γ -> activate macrophage

41
Q

Interferon (IFN)

A
  • effectors made by cells
  • “warning protein” made by leukocytes (especially dendritic cells) if they detect virus
42
Q

The IFN-α and IFN-β that are made by infected cells are detected by neighboring cells using the IFN receptors. What does this do?

A

It turns on about 300 genes we call IFN stimulating genes

43
Q

Type I Interferons (IFN-α and IFN-β ) local effects on other immune cells

A
  • induce resistance to viral replication in all cells
  • increase MHC class I expression and antigen presentation in all cells
  • activate NK cells to kill virus-infected cells
44
Q

‘Antiviral state’

A
  • turned on by Type I interferons
  • those cells become resistant to infection, which helps to contain the infection as well

eg. TRIM22 inhibits trafficking of HIV gag proteins

45
Q

All cells can make IFNs but those ________ dendritic cells make lots of IFNs than any other cell type

A

specialized

46
Q

2’-5’ oligoadenylate synthetase (OAS)

A
  • is activated to make oligoadenylate (AAAAAAA) which in turn activates RNase L
  • takes adenylase & makes a chain of them
47
Q

RNase L

A
  • degrades cellular and viral mRNA in that neighboring cell, suppressing infection
48
Q

dsRNA activated protein kinase (Pkr)

A
  • stops new protein synthesis
49
Q

Defense against intracellular pathogens by cytotoxic T lymphocytes

A
  • Cytotoxic T cell kill virally infected cells
  • The T cell will actually contact the virally infected cell & deliver a signal to kill that cell
50
Q

Cytotoxic T cells kill ______________, by killing the infected cell

A

intracellular pathogens

51
Q

The key point to understand some of the antiviral mechanisms

A
  • CTLs recognize viral peptides presented on MHC class I
  • IN a normal cell, proteins are getting chopped up, put on MHC class I and they go into the surface
  • When that cell gets infected by a virus, the viral protein will get presented on the outside of that cell & those viral proteins are seen by cytotoxic T cells
  • The key point here is these peptides are coming from newly synthesized proteins
52
Q

CTL kill by __________

A

apoptosis (forced cell suicide)
-clean cell death

53
Q

The activation of cytotoxic T cells requires three steps

A
  • cytotoxic T cells will go through many rounds of proliferation & differentiation if they get this T cell help
  • The initial activation of cytotoxic T cells involves an APC, because in order to prime naive CD8 T cell, you need both presentation of a peptide on an antigen presenting cell to T cell and you need the 2nd signal (co-stimulating signal)
  • Antigen stimulated CTL are activated to divide 7-10 times and differentiate into effector and memory T cells
54
Q

IL-2

A

T helper cells will make that IL-2 that is needed for proliferation of the cytotoxic T cells

55
Q

CTL effectors live for _________ while memory cells live for ________

A

CTL effectors live about a week
Memory cells live for many years and are present if virus re-infects

56
Q

Memory cells are made only if

A

CTL is primed by IL-2 from a T helper.

57
Q

Very young & very old age are ______(more/less) susceptible to disease from viruses

A

more

58
Q

Cytotoxic T cells (serial killers) kill only targets bearing _______________

A

specific non-self antigen

viral antigens are expressed on infected cells

59
Q

Does a CTL get damaged in the killing process?

A

No, it can kill and kill

60
Q

Natural killer (NK) cells

A
  • look just like T cells
  • are also cytotoxic lymphocytes
  • play a critical role in the early innate response to viruses
  • have the same lytic molecules as CTL
61
Q

what inhibits NK killing?

A

Engagement of MHC class I by NK inhibitory receptor inhibits killing

62
Q

What activates NK killing?

A

Down regulated MHC class I results in activation of NK killing

Viruses often down-regulate surface expression of MHC. This makes them a target of NK cells

IMIN 200 (20 decks)

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