16 Immunity - viral infections Flashcards
(110 cards)
1
Q
what are the different types of outcomes for virus infections
A
Some virus infections are pathogenic and cause disease
Some viruses are persistent and cause long-term health problems
2
Q
how are viruses broadly split
A
broadly split into DNA or RNA viruses
3
Q
virus split imapct
A
impacts host recognition and immunity
4
Q
what can DNA virus use
A
can use host polymerases and goes to the nucleus
5
Q
what can RNA virus use
A
has its own RNA polymerase and replicates in cytoplasm
6
Q
what is EBV
A
Epstein-barr virus
7
Q
what is HCV
A
Hep C virus
8
Q
DNA viruses replication
A
- Deliver viral DNA to the nucleus
- Replicate using viral or host DNA polymerases
- Generate DNA intermediates
- DNA can accumulate in cytoplasm - Can have very small genomes, or very large genomes
- Can result in cell lysis
9
Q
RNA viruses replication
A
- Replicate in the cytoplasm
- Use viral polymerases
- Generate double-stranded RNA intermediates
- RNA accumulates in cytoplasm - Generally have very small genomes
- Can result in cell lysis
10
Q
what can DNA virus replication cause directly
A
Can cause cancer directly
11
Q
what can DNA virus replication cause indirectly
A
Can cause cancer indirectly
12
Q
DNA virus direct cancer example
A
Viral oncogenes affect cell cycle
13
Q
DNA virus indirect example
A
HBV
14
Q
what can RNA virus replication cause directly
A
Can cause cancer directly
15
Q
what can RNA virus replication cause indirectly
A
Cause cancer indirectly
16
Q
RNA virus indirect example
A
HCV
17
Q
RNA virus direct example
A
Retrovirus integration
18
Q
what are chronic and acute infections controlled by
A
This is controlled by interplay between the virus and host immune system
19
Q
what diseases are controlled by chronic and acute infections
A
HCV
HBV
20
Q
what diseases are controlled by other viruses always establish chronic infection
A
HIV
21
Q
Acute infections
A
Flu
RSV (important childhood infection)
Gastroenteritis
Infection of skin
22
Q
Chronic infections
A
Infect immune system eg HIV,
Viruses can infect T cells
Chronic infection associated with small number of organs
23
Q
acute virus infections equilibrium state
A
non-equilibrium state
24
Q
what controls acute viral infections
A
Viral replication and host immunity control the dynamic
25
acute viral infections characteristics
rapid replication, generation of virions, and spread
26
Chronic virus infections equilibrium state
More equilibrium state than acute infections
27
chronic infection persistance
Virus is able to persist in the presence of host immunity
28
what is important about the chronic infection
Essential to evade the immune response, or become a latent infection
29
how is chronic infection characterised
progressive replication, suppression of immune responses
30
Types of chronic infections
latent
chronic
slow
31
example of latent
Herpes simplex virus
32
example of chronic
Hepatitis C virus
| Hepatitis B virus
33
example of slow
Measles infection of the nervous system
34
what virus displays all three phenotypes of chronic infections
retroviruses
35
Latent
completely quiet, suppress themselves
36
Chronic persistent
constantly producing virus particles
37
Slow
replication so cause less immune response
38
Sites of chronic virus infections
Neuronal cells/CNS
Liver
Immune cells
39
Innate sensing
Virus-associated molecules recognised by the immune system:
1. Viral proteins
2. Viral nucleic acid (dsRNA; 5’triphosphate RNA)
3. Infected cells
4. Altered host proteins
40
Innate sensing PAMPs associated
Some are associated with the virion (particle itself)
| Some are associated with viral replication
41
where is RNA genome in virion
RNA genome is contained in a nucleocapsid
42
Components of a virion examples
Not all viruses have all these, but examples
- Reverse transcriptase
- Protease
- Integrase
- Vpr
43
what is protease for
break down host cell proteins
44
what is integrase for
integrate into host cell genome
45
what is Vpr
accessory protein
46
what encloses the nucleocapsid
capsid encloses it
47
where is the matrix
matrix protein exists between the capsid and the envelope
48
what is the virion lipid envelope populated with
virion lipid envelope is populated with viral attachment factor
49
where are host cell proteins
Host cell proteins are also incorporated into the virion
50
Sensing virus particles - detection
On infection with a virus particle, these viral proteins can be detected.
Virions are present in sites of infection, or systemically
51
Sensing virus particles - recognition by lectins effects
Neutralization
| Complement activation
52
Sensing virus particles - recognition by antibodies
Neutralization
| Complement activation
53
Sensing virus particles - APC
Binding of B cells to viral antigens – B cell receptor
| Binding of macrophages/dendritic cells to virus particles – lectin receptors; Fc receptors; TLRs
54
T/B cell activation in virus infections
```
APC activates T helper cells
Th2 activates the B cells
Get production of cytokines from Th1
Activates CTL’s which the recognise infected host cells
CTL’s then kill infected host cells
```
55
Innate sensing of infections examples of important classes
Toll-like receptors (TLRs)
Rig-like receptors (RLRs) (associated with recognising RNA)
Cyclic dinucleotide receptors (CDRs) (associated with recognising DNA)
56
Innate sensing of infections - detection
Virus infections are initially detected by different pattern recognition receptors
57
Interferon-stimulated genes - major effector functions of ISGs
1. Reduction in transcription of viral RNA
2. Reduction of virus protein expression
3. Degradation of dsRNA
4. Editing of viral RNA
5. Modification of viral proteins
58
what do type I IFN make
```
immature DC
macrophage
Th1 and NK
epithelial cells/fibroblasts
inflammatory cell
```
59
immature DC effect - type I IFN
activation
migration
IL-12 production
60
macrophage effect - type I IFN
induction of antiviral genes
| death sensitization
61
Th1 and NK cells effect - type I IFN
IFN-gamma expression
62
epithelial cell or fibroblasts effect - type I IFN
inhibition of viral infection
63
inflammatory cell effect - type I IFN
enhanced septic shock
64
PKR
protein kinase receptor
65
what induces PKR
PKR is induced by IFN
66
what does PKR recognise
Recognises dsRNA associated with virus replication
67
what does PKR do
Phosphorylates eIF2a, inhibiting protein expression
| Recruits caspases, triggering apoptosis
68
what does PKR activate
NFkB, promoting inflammation
69
tetherin act against
against enveloped viruses
Binds to the surface glycoproteins
Act against a wide range of viruses (retroviruses; ebolaviruses)
70
what does tetherin prevent
Prevents release of the virus while budding – stop being spread
Retained particles are targeted for degradation
71
what does tetherin sense
senses enveloped viruses, triggering inflammation
72
Innate immunity - viral infections
1. Innate immunity is not sufficient for control of all virus infections
2. Pathogens evolve quicker than complex hosts and can escape innate immunity
3. Evolution of an adaptive immune response allows the host to rapidly react to different viruses
73
Cellular recognition of infected cells
- activate of APCs
- induction of an antiviral state
- killing of virus-infected cells
74
Cross-presentation of viral antigens - direct presentation
Direct display of viral antigens on infected cells activates T cells
75
Cross-presentation of viral antigens - cross-presentation
Dendritic cells can also display fragments of soluble antigens on MHC class I
76
Cross-presentation of viral antigens - cross-dividing
Utilising trogocytosis, DCs can acquire MHC class I-loaded peptides for presentation to memory T cells
77
CD8+ cells are activated by
MHC I expressed viral peptides
78
what does CD8+ cells make
Perforins
Granzymes
Granulysin
79
Antiviral effects of antibodies
1. neutralisation
2. complement lysis
3. opsonization and phagocytosis
4. ADCC
80
NK cell effectors
Perforins
Granzyne
a-defensins
81
what do NK cells secrete
IFN I, II
82
Viral mechanisms for evading host immunity
1. Replication in privileged sites
2. Protease cleavage of host innate immunity proteins
3. Blocking ISGs
4. Down-regulation of immune mediators
5. Triggering immune tolerance
- Host mimicry
- Glycosylation
6. Rapid mutation
7. Latent infection
83
Replication in immune privileged sites
Some tissues have blood-tissue barriers that prevent immune cells from transmitting
84
Replication in immune privileged sites - examples
Replication in the retina
Replication in CNS
B cell follicles
85
how can viruses 'hide'
Viruses can also compartmentalise a cell to evade innate sensing
HCV replicates in ‘double-membrane vesicles’
86
Viruses inactivate PKR
Many viruses block the signalling pathway that results in PKR blocking of eIF2a translation
Most block the dimerization or action of PKR directly
87
Viruses evade Tetherin
```
Tetherin has been co-opted for the entry pathway of CMV
Block tetherin
- HIV
- Dengue
- Ebola
```
88
HCV evasion of innate immunity - replication
Replicates in the liver
- Tolerant site
- Target cells are hepatocytes
89
HCV evasion of innate immunity - virion and lipoproteins
Virion associates with lipoproteins
| Enhance infection and prevent recognition by humoral immunity
90
how does HCV evasion of innate immunity inactivate intracellular recognition
Has a range of mechanisms to inactivate intracellular recognition
91
Protease cleavage of host innate proteins
Cleaving some of the host proteins
To get individual proteins it needs to function
have recognition sites in TRIF and MAVS
92
Mutation rate
RNA-dependent RNA polymerase has no error checking
| High viral turnover and error-prone replication leads to variation
93
Latent infection – HSV1
1. primary site of infection: productive infection of epithelial cells
2. secondary site of infection and site of latent infection: sensory neuron
3. site of recurrent infection: productive infection of epithelial cells
94
‘Latency-associated transcript’ inhibit
cell death and establishes latent infection
95
‘Latency-associated transcript’ alters
DNA binding to histones, preventing gene expression
96
Tissue specificity is defined by
the surface haemagglutinin (HA) protein
97
Influenza pathogenesis transmitted
Transmit in air droplets, penetrating the respiratory mucin layer and binding to airway epithelial cells
98
Influenza haemagglutinin specificity
Specificity for different sialic acid types
99
Influenza haemagglutinin
Allow the two membranes to fuse to allow them to invade
- cell membrane
- viral membrane
100
Cleavage of HA - replication
Replication is usually restricted to epithelial cells of the upper and lower respiratory tract
101
Variation is essential to continued spread of influenza virus
New variants are not recognised by host immunity
Immunity to specific strains prevents infection
This permits selective transmission of new variants
102
Influenza possesses two different mechanisms for variation
Antigenic drift
| Antigenic shift
103
Antigenic drift cause
amino acid changes in immunogenic sites of HA/NA
104
Antigenic shift cause
recombination of different HA/NA gene segments
105
Antigenic drift responsible for
seasonal variations in the H1N1 and H3N2 strains
106
Antigenic shift responsible for
emerging pandemics
107
antibody-mediated immune control vaccine-induced adaptive immune examples
Influenza
(inactivated vaccines)
Hepatitis B virus
(recombinant vaccine)
108
antibody-mediated and cell-mediated immune control vaccine-induced adaptive immune examples
Measles
(attenuated vaccine)
Rotavirus
(attenuated vaccine)
109
why use antibody-mediated vaccine
antibody important for protection
110
why use antibody-mediated and cell-mediated immune control
Combinations of cellular and antibody response contribute to clearing virus particles and infected cells
