Lecture 11 Flashcards

1
Q

what is CPE?

A

cytopathic effects

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2
Q

what are some cytopathic effects (CPE) or virus infection?

A
  • inhibition of DNA, RNA, and protein synthesis (cytolytic viruses do this)
  • damage to cell lysosomes, release of digestive enzymes
  • alteration of plasma membranes (results in enhanced susceptibility to immune system)
  • cytotoxic effect of accumulation virus proteins: cytoplasmic and nuclear inclusions
  • introduction and inhibition of apoptosis
  • transformation of host cell into malignant cell
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3
Q

Can immune cells kill virally infected cells?

A

yes

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4
Q

briefly describe T-cell receptors

A

can recognize the peptide that is presented on the cell surface, and if it does it with secrete molecules that cause the lysis of that cell

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5
Q

briefly describe antibodies

A

binds to surface of viral glycoproteins and can recruit complement components that, when activated by binding to the antibodies, can form a membrane attack complex and make a big hole/lyse the cell

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5
Q

briefly describe NK (natural killer) cells

A

can recognize when antibodies are bound to a cell recognizing the Fc portion through their Fc receptors.

they bind this and also release molecules that can locally lyse these infected cells

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6
Q

what are two major pathways that can lead to cell death?

A

apoptosis and necrosis

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7
Q

True or False: viruses can induce both apoptotic and necrotic pathways to kill cells

A

true

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8
Q

from a cellular perspective, is necrosis passive or regulated?

A

necrosis is a relatively passive process

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9
Q

from a cellular perspective, is apoptosis regulated or a passive process?

A

it is a highly regulated process

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10
Q

how can necrosis be induced?

A

can be induced by severe insults to a cell such as heating, cooling, extremes of pH and other physical and chemical trauma

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11
Q

what is the end result of necrosis?

A
  • loss of membrane integrity and “spilling” of cell contents into the extracellular environment
  • this is viewed as a danger signal by the immune system and generally elicits a robust inflammatory response
  • this is important for initiating an adaptive response to infection, but can also lead to immunopathology
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12
Q

what is apoptosis and how is it accomplished?

A
  • it is programmed cell death
  • accomplished by a cascade of biochemical steps that culminates in cell fragmentation and eventual engulfment of these fragements by phagocytic cells
  • can release toxic compounds (reactive oxygen species) good for eliminating bacteria but also starts inflammation
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13
Q

what is one clear distinguishing feature between apoptosis and necrosis?

A

unlike necrosis, cell membranes remain intact and a robust inflammatory response is not initiated by the host. apoptosis is a “natural” process used

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14
Q

is the following sentence an example of apoptosis or necrosis: during development to eliminate unwanted cells

A

apoptosus

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15
Q

what is necrosis?

A

it is the “forced” death of body cells due to some sort of trauma

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16
Q

how can apoptosis be used in terms of misbehaving cells in the body?

A

apoptosis can be used to eliminate misbehaving cells from the body (ex. those that have suffered serious dna damage or those that display signs of cell cycle deregulation)

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17
Q

what is the connection between viral infection and apoptotic responses?

A
  • virus infection frequently induces an apoptotis response inside infected cells and many viruses have developed mechanisms to circumvent apoptosis
  • under some circumstances viruses can also directly induce apoptosis in infected cells, here the timing is critical however
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18
Q

what must happen in order for a virus to persist in a host population? why?

A
  • there must be a balance between the severity of disease caused by the virus and the ability of the host to clear the infection
  • if the virus kills the host too effeciently it will quickly run out of new hosts and be unable to persist in the population
  • but if the host clears the virus effeciently, the virus will be unable to persist in the host populations
  • the immune system plays a critical role in this delicate balance
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19
Q

how quickly do innate immune responses occur?

A

occur within minutes to hours after exposure to the pathogen

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20
Q

what is the importance of innate immune response?

A

critical for restricting the spread and amplification of the invading pathogen

21
Q

how long does it take for the adaptive immune response to kick in?

A

it takes days-weeks to become established

22
Q

what is the importance of the adaptive immune response?

A

critical for clearing the infection from the host an for providing and immediate response to reinfection by the same pathogen (memory)

23
Q

what is the chain of barriers to virus infection?

A

intrinsic defense, innate immunity defense, acquired immunity defense (in that order)

24
Q

how are intrinsic cellular antiviral resistance mechnisms defined?

A

pre-existing cellular factors or mechanisms that recognize virus infection and can act immediately to thwart virus replication

25
Q

what do intrinstic cellular antiviral resistance mechanisms represent?

A

a first line of cellular defenses against viral infections

26
Q

What do intrinsic cellular antiviral defenses include?

A
  • apoptosis
  • autophagy/xenophagy
  • host restriction factors
  • epigenetic transcription silencing of viral genomes (DNA viruses
27
Q

what is autophagy/xenophagy?

A
28
Q

what are components of the innate immune system?

A
  • cytokines
  • centinel cells (ex. dendritic cells and macrophages)
  • natural killer cells
  • complement
29
Q

what are cytokines?

A
  • soluble proteins released from cells
  • regulatory proteins that mediate critical processes intracellular communication utilized in the etablishment of antiviral defenses
  • play critical role in the development, maintenance, and regulation of adaptive immune responses
30
Q

what does SAMHD1 do? what does vpx do?

A

SAMHD1 is a cellular protein that functions to limit the availability of dNTPs in cells (not usually needed)

If the cell is infected with a retrovirus, you need dNTPS to synthesize the dsDNA, so the virus cant replicate

so retrovirus brings in a protein called vpx that recruits an enzyme that adds ubiquinone to SAMHD1, basically makes it marked for disposal. now you can make dNTPS required for the virus

IF YOU MUTATE THIS VIRUS TO NOT HAVE VPX, ITS “TOAST” (cant replicate)

31
Q

what do pro-inflammatory cytokines promote?

A

they promote leukocyte activation

32
Q

what do anti-inflammatory cytokines do?

A

suppress the activity of pro-inflammatory cytokines, return system to basal “circulate and wait” state
(reverse activation of immune cells)

33
Q

what do chemokines do?

A

certain immune cells respond to certain chemokines, meaning they migrate towards where the chemokines are produced (conc. gradient)

therefore they recruit immune cells during early stages of immune response

34
Q
A
35
Q

What are the three general classes of cytokines?

A
  • pro-inflammatory
  • anti-inflammatory
  • chemokines
36
Q

what are interferon proteins considered?

A

considered to be cytokines, but are “special”

37
Q

How can virally infected cells be prompted to produce a variety of cytokines?

A

achieved through signalling pathways that lead to the activation of a transcription factor called NF-kappa B

38
Q

What are the roles of pro-inflammatory cytokines?

A

promote leukocyte activation

39
Q

what are the roles of anti-inflammatory cytokines?

A

suppress activity of pro-inflammatory cytokines, return system to basal “circulate and wait” state

40
Q

what are the roles of chemokines cytokines?

A

recruit immune cells during early stages of the immune response

41
Q

what is an interferon?

A
  • can be produced when exposed to a virus
  • it is known as “inhibitor interferon”/IFN
  • proteins made and released by host cells in response to the presence of pathogens such as viruses
  • IFNs are the most important cytokines in the innate response against viral infection
42
Q

how do cells produce IFNs?

A
  • when exposed to virus
  • achieved through the activation of signalling pathways that converge on the transcription factors IRF3 and IRF7 (IRF means interferon regulatory factor)
  • cells respond to IFN by establishing an “anti-viral” state within the cell
43
Q

how do cells respond to IFNs?

A

establishes an “anti-viral” state within the cell (important in combating infection)

44
Q

What are the most important cytokines/response in the innate response against viral infection?

A

interferons

45
Q

Are IFNs in themselves an antiviral?

A

no

46
Q

what does the detection of IFNs lead to?

A
  • intiates a very well characterized signal transduction pathway that can lead to the increased expression of around 300 genes
  • which genes are expressed depends on the cell type stimulated and the type of interferon doing the stimulation
47
Q

What are ISGs?

A
  • interferon stimulated genes
  • have no known function when stimulated, but many of the ones we know about play key roles in setting up what is called “antiviral state” within the cell
48
Q

what are PAMPS?

A
  • pathogen associated molecular patterns
  • inlcude things such as LPS, flagellin, dsRNA, ssRNA, etc
49
Q

What is important about the PAMPs?

A
  • their location is important
  • the location of PAMP receptor and the PAMP itself is what makes it uniqye
50
Q

What recognizes PAMPS?

A

two general classes of pattern recognition receptors:
* toll like receptors expressed predominantly in antigen presenting cells like dendritic cells and macrophages. found either on the cell surface or in endosomal membranes
* cytoplasmic RNA helicases RIG-I and Mda5 are widely expressed in tisuses and are activated upon binding dsRNA

51
Q

do pattern recognition receptors have similar pathways?

A

yes, both signal through similar pathways to elicit the production of cytokines