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MIIM30003 - Medical & Applied Immunology > Lecture 9 - Viral Immunity I > Flashcards

Lecture 9 - Viral Immunity I Flashcards

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USMLE® Step 1 flashcards
1
Q

Describe the first line of defence against viral pathogens

A 
1. Physical barriers:
 • Keritanised epithelial cells
 • Tight junctions
 • Mucociliary escalator
 • Longitudinal flow of air and fluid
 • Tears
2. Chemical barriers:
 • Low pH on skin and stomach
 • Fatty acids on skin
 • Mucous
 • Lysozyme in tears
 • Pepsin in stomach
  1. Soluble proteins
    • Defensins
    • Collectins
    • C’
  2. Cells
    • Alveolar macrophages
    • PMNs
  3. Microbiological
    • Normal flora occupying the niche
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2
Q

List the various routes of entry to viral pathogens, and list a few that exploit each route

A 
Respiratory tract:
 • Influenza
 • Rubella
 • Mumps
 • Measles
 • Adenoviruses
 • RSV
 • Rhinoviruses

Conjunctiva:
• Adenoviruses
• HSV

UGT:
 • HIV
 • HBV
 • HSV
 • CMV
 • HPV
GIT:
 • Rotavirus
 • Norovirus
 • HAV
 • Caliciviruses
 • Adenoviruses

Skin:
• HSV
• HPV
• West nile virus

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3
Q

Describe the action of defensins

A

Two subtypes:
1. α-defensins
• Present in neutrophils

  1. β-defensins
    • Present on epithelia

Amphipathic molecules

Insert into cell membranes, creating a pore

Result in lysis of cell

NB only good for enveloped viruses (HIV)

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4
Q

Describe the action of collectins

Give examples of collectins

A

Structure:
• Protein
• Carbohydrate binding group

Examples:
• Mannan-binding lectin
• Surfactant protein A
• Surfactant protein D

Function:
1. Aggregation of particles
• A type of opsonisation

  1. Neutralisation
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5
Q

What type of molecule are collectins?

A

Soluble PRRs

Belong to C-type lectin superfamily

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6
Q

Describe the action of C’

A

C’ components present in the serum

C’ binds to surface of pathogens and becomes activated

Effector function:
• Inflammation (C3a, C5a)
• MAC formation (C56789)
• Opsonisation (C3b)

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7
Q

Describe how the various subsets of macrophages protect against viral infections

A

Alveolar macrophages:
• Capture viruses in respiratory tract

Subcapsular sinus macrophages & Marginal zone macrophages
• Present in LNs
• Prevent further spread of viruses

Release IFN and cytokines that limit viral replication and prime immune response

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8
Q

What was observed in mice lacking sub-capsular sinus macrophages?

A

Viruses were able to spread from LNs to nerves

VSV (vesicular stomatitis virus) spreads to nerves and causes paralysis

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9
Q

Describe, in general, the role of innate immunity in viral infection

A

Type I IFN

NK cells

Stem the spread of viruses in the first few days while the adaptive immune response is being primed

Stems the spread, but cannot fully remove the infection

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10
Q

Describe the sensing of viruses

What does this trigger?

A
  1. PRR-PAMP ligation

PRRs:
1. NLRs
• Cytosolic
• Detect viral DNA/RNA

  1. RLR
    • Cytosolic
    • Detect viral DNA/RNA
  2. TLRs
    • Membrane associated
    • Detect viral DNA/RNA
  3. Signal transduction
    • NFKB
    • IRF
  4. Transcription of type I IFN and pro-inflammatory cytokines
  5. Induction of the anti-viral state; inflammation
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11
Q

Which pro-inflammatory cytokines are produced in response to PRR-PAMP ligation?

A 
IL-1
IL-6
IL-12
IL-18
TNFa
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12
Q

Describe the effects of type I IFN

A

‘Anti-viral state’

IFN binds receptors on the surface of all cells

S-T pathway through JAK/STAT

  1. Inhibition of viral protein synthesis
    • Activation of PKR
    • Inhibition of eIF2a (through phosphorylation)
  2. Increased Ag presentation on MHC I
    • Immunoproteasome
  3. Degradation of viral RNA
    • Activation of 2,5-Oligo A synthetase
    • Activation of RNAseL
  4. Inhibition of virion assembly
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13
Q

Describe the role of NK cells in viral infections

A
  • Key mediators of viral immunity -

Inhibitory receptors:
• KIR

Activation receptors:
• NKG2D
• Ly49
• CD16

  1. Virus infected cells down regulate MHC I and express viral glycoproteins
  2. NK cells interrogate cells; do not receive inhibitory signals through KIR and receive activation signals (viral glycoproteins) through NKG2D
  3. NK cells become activated and kill infected cells (perforin dep.)
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14
Q

Which cytokine do NK cells predominantly produce?

A

IFN-gamma

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15
Q

Describe adaptive immunity to virus infections

A

T cells:
• CTLs recognise virus infected cells specifically and kill them (perforin dep.)
• ‘Helper’ T cells help CTLs and B cells

B cells:
• Generate Ab against virus
• Neutralisation of virus particles
• Agglutination of virus → phagocytosis

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16
Q

Describe how lymphocytes become activated in viral infections

A

Requires DCs

DCs must present viral Ag to lymphocytes in lymphoid tissues:
• Direct infection of DCs
• Cross-presentation

  1. DC activation in tissues
  2. Upregulation of CCR7 and down regulation of adhesion molecules
  3. Migration through lymphatics to lymphoid organs
  4. Entry into paracortex of LNs through afferent lymph
  5. Interaction with T cells; immunological synapse
17
Q

Describe the immunological synapse

A

Interaction between DCs and T cells

Adhesion:
• LFA-1 and ICAM-1

Signal 1:
• MHC:Ag and TCR
• MHC II and CD4 T cells
• MHC I and CD8 T cells

Signal 2: Costimulation
• CD80/86 on DC
• CD28 on T cell

Signal 3:
• Cytokines released by DCs
• IL-2

18
Q

Describe CD4 T cell help for B cells

A

Activated CD4 T cells express CD40L

Th cells stimulate B cells through CD40L-CD40 interaction

B cells now undergo the maturation events (SHM, CSR) to be able to generate an effective immune response

19
Q

How do CTLs kill virus infected cells?

A
  1. Perforin & granzymes
  2. Cytokines
    • IFN-gamma
    • TNFa

The cytokines may result in purging cells of virus w/o killing it. This may be especially important in infection of neurons

20
Q

Describe how Ab can play a role in viral immunity

A
  1. Neutralisation
  2. Opsonisation
  3. C’ activation
  4. ADCC
21
Q

Compare Ab presence in serum and secretions

A

Serum: IgG

Secretions: IgA

22
Q

Which cells have FcRs?

A

Macrophages
NK cells
PMNs

23
Q

How is an individual protected against future infections of the same virus?

A
  1. Stable Ab titres in serum and secretions
  2. Pool of memory T cells:
    • T(CM)
    • T(EM)
    • T(RM)
24
Q 
Compare the following features of the various subsets of memory T cells:
 • Location
 • Recirculation
 • Effector function
 • Proliferation
A

Location:
• T(CM): blood and 2° lymph. organs
• T(EM): blood and extra lymphoid tissues
• T(RM): skin and mucosae

Recirculation:
• T(CM): high
• T(EM): high
• T(RM): low

Effector function:
• T(CM): low
• T(EM): high
• T(RM): high

Proliferation:
• T(CM): high
• T(EM): low
• T(RM): low

25
Q

What is the role of T(RM) cells?

A

Remain localised in the skin and mucosa

Capable of rapidly responding to invaders

May have an important role in localised infections

26
Q

Which PRRs recognise viral Ags?

A

TLRs:
• 2, 3, 4, 7, 8, and 9

RLRs:
• RIG-I
• MDA-5
• LGP2

NLRs:
• NLRP3 inflammasomes
• AIM2

27
Q 
Which components of virus do the following detect:
 • TLR2
 • TLR3
 • TLR4
 • TLR7
 • TLR8
 • TLR9?
A

TLR2: unknown ligand

TLR3: dsRNA

TLR4: glycoprotein F of RSV

TLR7 & 8: ssRNA

TLR9: CpG DNA

28
Q

Which components of viruses do the following detect:
• RIG-I
• MDA-5
• LPG2?

A

RIG-I:
• Short dsRNA
• ssRNA

MDA-5: longer dsRNA

LPG2: facilitates MDA-5 and RIG-I

29
Q

Which components of the following detect:
• NLRP3 inflammasomes
• AIM2?

A

NLRP3: large number of stimuli

AIM2: cytosolic dsRNA

MIIM30003 - Medical & Applied Immunology (30 decks)

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