Immune response to virus infection Flashcards

1
Q

what antiviral cytokines do infected cells and plasmacytoid dendritic cells produce?

A

type I interferons alphas and beta

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2
Q

How do plasmacytoid dendritic cells detect viral nucleic acids?

A

TLR7 and TLR9

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3
Q

How do infected cells detect viral nucleic acids?

A

RIG-I and Mda-5

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4
Q

What to IFN alpha and bets do?

A

inhibit viral replication by inducing ezpression of:

dsRNA activated protein kinase (PKR)

oligoadenylate synthetase

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5
Q

how does PKR work to inhibit viral replication?

A

activated by dsRNA
inactivation of eIF-2alpha (translation factor)
inhibition of protein synthesis

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6
Q

How does oligoadenylate synthetase work?

A

activated by dsRNA
activates RNAse L
degradation of viral RNA

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7
Q

How do IFN alpha and beta facilitate immune response to viral infection/

A

promote expression of MHC class I

produce NK cells increasing cytotoxic activity

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8
Q

What are NK cells?

A

lymphocytes
granular morphology
recruited to viral infected sites
important role in early stages before CTLs

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9
Q

How do NK cells recognised virally infected cells?

A
  • lack specific receptors
  • express germ-line encoded receptors
  • stress induce expression of ligands for NK activating receptors - NKG2D receptors, UL16 binding proteins, MICA/B
  • virus downregulate MHC class I expression
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10
Q

What ligands are present that cause cells to be killed by NK cells?

A

NKG2D

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11
Q

What happens if cell lacks MHC class I?

A
Killed by NK cells 
lose MHC class I = lose inhibitory signal
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12
Q

Why is there a balance between expression of certain ligands and downregulation of MHC class I?

A

balance will determine HOW the NK cells kill the target cell

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13
Q

How do the contents of NK cells induce apoptosis?

A

granzymes

perforin - pores in membranes, granzymes can enter into cell cytoplasm and induce apoptosis

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14
Q

How do NK cells connect to the target cell?

A

form a lytic immunological synapse - polarise at synapse

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15
Q

How to granzymes from NK cells act?

A

DNA fragmentation - capsase activated DNAse
mitochondrial dysfunction

cleave proteins
targets pro-capsase 3

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16
Q

What causes dendritic cells mature?

A

Danger signal e.g. viral nucleic acid via TLR3

17
Q

Where do dendritic cells move from and to?

A

originally in periphery e.g. skin, mucosa

move to lymphoid organs - present antigens to T cells & express co-stimulatory molecules

18
Q

What is the only cell that can present antigen to naive T cells?

A

Dendritic cell

19
Q

What are the 2 types of cells that are made from clonal expansion?

A

Effector cells

Memory cells

20
Q

How do CTLs detect virally infected cells?

A

T cell receptor recognises peptides bound by MHC class I

only 1-3 complexes needed for detection

21
Q

How is MHC class I antigen presented inc ells?

A

viral antigens chopped by proteasome complex

translocated in ER

MHC class I folding

TAP association & peptide binding

loaded into MHC class I molecules

22
Q

How do CTLs kill infected cells?

A

forms immunological synapse

secretory lysosomes polarise to synapse

release perforin & granzymes

ESSENTIALLY SAME AS NK CELLS

23
Q

What cells secrete antibodies?

A
  • B lymphocytes

- plasma B-cells

24
Q

What are the antiviral activities of antibodies?

A

neutralisation
opsinisation
complement activation

25
Q

How do antibodies neutralise viruses?

A

bind to proteins on virus surface - prevents receptor binding on host cells

neutralise IgA antibodies in mucus - prevent virus infections

26
Q

How do antibodies opsinise viruses?

A

Fc receptor bind to Fc region of antibody-antigen complexes

Phagocytosis of immunoglobulin

27
Q

How do antibodies undergo complement activation

A

recruit complement proteins

complement-mediated neutralisation

complement-mediated virolysis

phagocytosis via complement receptors

28
Q

How do vaccines protect against pathogens?

A

viral antigens in attenuated or killed form

induction of memory cells

29
Q

What are the ways viruses evade the immune system?

A
  • interference with IFN alpha and beta
  • inhibition of NK cell recognition
  • inhibition of CTL recognition
  • inhibition of complement activation
30
Q

How do viruses inhibit the IFN alpha and beta response?

A

Lassa virus - removes the stimulus for activation, dsRNA

Adenovirus - inhibits IFN transcription

Vaccina - binds to IFN alpha - cannot bind to receptors

31
Q

How do viruses inhibit NK cell recognition?

A

HCMV - UL16 blocks expression of NK cell ligands - stay inside cell e.g. MICA

KSHV downregulates cell surface expression of MICA and MICB

32
Q

How do viruses inhibit presentation of MHC class I?

A

If peptides do not get into ER, they cannot be loaded onto MHC class I

33
Q

How do viruses inhibit complement activation?

A

Complement control proteins are encoded by host cells to prevent damage

KSHC generates own - impair complement activation & complement mediated manage to membrane

KCP - inhibits complement mediate lysis of KSHV virions