Respiratory week 1 Flashcards
1
Q
allergy
A
immune-mediated inflammatory response to common environmental antigens that are otherwise harmless
2
Q
atopy
A
genetic predisposition to allergy :
- high levels of IgE
- large numbers of eosinophils
- large numbers of IL-4 secreting Th2 cells
3
Q
allergen common features
A
- repeated exposure via mucosal route
- very stable
- high solubility in bodily fluids
- introduced in v low doses
4
Q
why dose of allergen important
A
if exposed to large amount of antigen - allergy less likely
relationship between dose of immunizing agent and production of allergy
5
Q
4 types of hypersensitivity
A
immediate hypersensitivity - Type 1
- antibody mediated - TypeII
- immune complex - Type III
- delayed type hypersensitivity - Type IV
6
Q
Type I hypersensitivity
A
immediate hypersensitivity IgE, mast cells and lipid mediators
7
Q
Type II hypersensitivity
A
antibody mediated
IgM and IgG against cell-bound or extracellular matrix Ag
8
Q
Type III hypersensitivity
A
immune complex - IgM and IgG immune complex deposition
complex can activate macrophages and inflammatory responses
9
Q
Type IV hypersensitivity
A
delayed type - CD4 mediated
10
Q
process of initial exposure to allergen
A
- bind allergen, engulf, process present on MHCII
- CD4 T cell responds - activation of T cell, upregulation of CD40L
- release of IL-4 - isotype switching of Bcell to produce IgE
- during clonal division some B cells memory cells, some plasma cells `
11
Q
second exposure to allergen - allergy
A
- IgE binds allergen
- Mast cells recognise through FcRs
- cross-linking of FcRs (brought in close proximity to each other)
- signalling in mast cell - large histamine release
12
Q
actions of histamine
A
vasodilation - swelling
sensitises nerve endings - itch
mucous hyperproduction - swelling
13
Q
immediate vs late phase reaction
A
immediate
- s/mins
- due to preformed mediators (histamine)
late
- peaks 8-12h
- induced mediators (chemokines, cytokines, leukotrienes)
- involve cell infiltrates and sustained edema and/or smooth muscle contraction
14
Q
hives sign you’re allergic?
A
no - can have hives without being allergic, but they are part of symptoms of allergic reaction
15
Q
systemic hypersensitivity reaction
A
anaphylaxis - mast cell response in blood - increases circulating histamine - vasodilation everywhere - decrease MAP - decreased perfusion of organs
16
Q
symptoms of anaphylaxis
A
- rapid breathing (due to lack of oxygenation of tissues)
- skin pale and bluish - centralisation (body tries to compensate by restricting blood vessels)
- unconsciousness due to lack of perfusion of brain - cease breathing - death
17
Q
mechanism of type Iv hypersensitivity
A
- antigen introduced into subcutaneous tissue and processed by local APCs
- Th1 T cells activated by antigen presenting cell
- releases cytokines and chemokines - act on vascular endothelium
- recruitment of T cells, phagocytes, fluid, protein
18
Q
e.g of type IV hypersensitivity
A
tuberculin test - detects presence of Tbc-specific CD4 T cells
coeliac disease
19
Q
coeliac disease
A
type IV hypersensitivity:
- mix of allergic and autoimmune: - antibodies against deaminated gluten - transglutamase 2 specific Abs
local chronic inflammatory response leads to villi atrophy, malnutrition, diarrhoea
20
Q
genetic disposition to coeliac disease
A
HLA-DQ2.5
this particular MHCII better at presenting transglutamase 2 in cleft due to shape
21
Q
4 treatments of allergy
A
- adrenline (alaphylaxis, asthma)
- inhaled B-adrenoceptor ag (asthma)
- antihistamines (hives, allergic rhinitis)
- leukotriene R antagonists (allergic rhinitis, asthma)
22
Q
corticosteroids
A
broad immunosuppression
- topical or systemic
suppress chronic inflammation by blocking gene transcription
23
Q
disadvantages of corticosteroids
A
non-specific with side effects: osteoporosis, weight gain, Type II diabetes
- effectiveness wanes over time
24
Q
allergic immunotherapy/ desensitization
A
continually exposed to increasing levels of antigen
- get immune tolerance
- reduced IgE, mast cell and basophil no.
- increase in Treg - blunt response
- more balanced Th1/Th2 responses
25
immunotherapeutic treatments for allergic asthma
- induce Treg - by desensitization
- anti-IgE (antibody against IgE)
- block IL-5 - skew response to Th1
26
airflow obstruction - what do you notice
1. increased sensation of breathing
2. increased respiratory muscle effort
3. active exhalation
4. longer time to inspire and expire
27
obstruction causes increase in load or drive
what does this lead to
load
leads to increase in work of breathing (WOB)
(anxiety causes increase in drive)
28
inspiration negative or positive pressure ventilation
negative
29
intrapleural pressure always intra-alveolar pressure
30
3 consequences of airway obstruction leading to increased WOB
1. recruitment of accessory muscles of inspiration (scalene and sternomastoid)
2. increased O2 consumption by respiratory muscles
3. risk of respiratory muscle fatigue, if the airway obstruction is severe
31
one important cause of ventilatory failure
| Pa of O2 and CO2
respiratory (inspiratory) muscle fatigue
| PaO2>60mmHg, PaCO2>50mmHg
32
exhalation active or passive?
| when active?
normally passive
active - abdominals and internal intercostals - exercise/significant airflow obstruction
33
spirometry
measurement of forced expiratory volume vs time
34
airflow obstruction - what happens to FEV1 and FEV/FVC and FVC
reduced FEV1 and FEV1/FVC
| same FVC, just takes longer
35
vital capacity
difference between TLC and residual volume
36
what happens if airflow obstruction causes uneven ventilation
get V/Q mismatch
| ventilation becomes un-homogeneous, perfusion also un-homogeneous as compensatory mechanism (try to limit V/Q mismatch)
37
V/Q matching
ventilation/perfusion matching
| =1 in all individual alveolar-capillary (A-C) units
38
low V/Q units
units that receive relatively less ventilation than perfusion
39
result of low V/Q units
oxygen binding sites may not be all filled - some blood returning to left atrium not fully oxygenated
40
2 ways of overcoming hypoxic effect of low V/Q
reduce blood flow
| increase conc. of O in air
41
shunt
extreme form of low V/Q unit (V/Q=0)- no airflow at all, airway completely blocked
42
randomization
random allocation of subjects into each arm with the objective of treatment groups being identical in all aspects other than the intervention. Primary rationale is to reduce selection bias
43
blinding
non-awareness of intervention allocation, with the aim to reduce information bias
44
intention to treat analysis
assume subjects remained in group to which they were randomised, regardless of actual treatment received, drop-out, loss to follow-up or cross-over. To reduce selection bias. So as to always under-estimate the treatment effect
45
NNT=
1/(absolute risk or rate reduction)
46
systematic review
is a type of literature review that collects and critically analyzes multiple research studies or papers
47
meta-analysis
statistical aspect of a systematic review
48
PICOT parameters
```
population
intervention
comparator
outcome
time
```
49
diagnstic test vs screening test
diagnostic - confirmation of disease or otherwise (clinical suspicion)
screening - identification of patients who may have disease (NO clinical suspicion)
50
sensitivity
% people with disease that test positive
51
specificity
% of people without disease that test negative
52
positive predictive value
% positive tests that are truly positive
53
negative predictive value
% negative tests that are truly negative
54
PPV and NPV are dependent on
- sensitivity and specificity
| - underlying prevalence of disease
55
PPV positively correlates with what
underlying prevalence of disease
56
likelihood ratio
likelihood that given test result would be expected in patient with the disease compared to patient without disease
57
main locations of mast cells
body sites in contact with external environment - skin, gut lung
- close to blood vessels/nerves/glands
58
external stimuli of mast cells
stings, allergen (IgE), polybasic drugs (morphine, vancomycin), mechanical stimulation, UV light/heat, osmotic stimuli - hypertonic saline
59
internal stimuli of mast cells
activated complement - c3a and c5a
| neuropeptides(from sensory nerves)
60
allergen induced mast cell degranulation mechanism
cross linking of IgE bound FCeR1
| (requires antigen-specific IgE produced in atopic subjects
61
transduction of IgE pathway in mast cells
adjacent - - IgE molecules bind allergen
- adjacent IgE receptor FceR1 cluster
- beta and gamma chains phosphorylated (internal)
- recruitment and activation of cellular tyrosine kinases
- PLC phosphorylation and activation
- DAG - PKC
- and IP3 - Ca mobilisation
- mast cell degranulation
62
immediate effects of mast cell activation
| - time course
- histamine
- heparin
- tryptase
- TNFalpha
30-45s
63
rapid effects of mast cell activation
| -timecourse
cys-LTs
PGD2
10-30 mins
64
slow effects of mast cell activation
| - timecourse
```
IL-4
IL-5
GM-CSF
- T-cell adn eosinophil dependent reaction
days
```
65
histamine actions on H1 receptors
```
pain and itch
bronchconstriction
mucous secretion
vasodilation - hypotension
increase vascular leak - hypovolemia
CNS - wakefullness
```
66
histamine actions on H2
positive ionotropic and chronotropic
| gastric acid secretion
67
what cells produce cysteinyl leukotrienes
eosinophils, mast cells, macrophages
68
cysteinyl leukotrienes made up of what, how
conjugation of glutathione with lipid
| glutathion-S-transferase - LTC4 from LTA2
69
stimuli for cysteinyl leukotriene production
allergen, C5a, platelet activating factor (PAF)
70
where does LTC4 act
CysLT1
71
pathological roles of cysLTs
vasodilator in skeletal muscles, airway obstruction, nasal obstruction
72
why delay in cysLTs
PLA2 - has to de-esterify acy lipid stores
73
activity of cysLTs determined by what 3 factors
1. amount of PLA2
2. signal transduction - Ca/MAPK activity
3. levels of inhibitors (annexin-1)
74
what is delayed and protracted release from mast cells
cytokines - ILs, TNF, chemokines, colony-stimulating factors
75
what does mast cell cytokine release cause
gene expression changes - inflammatory cell infiltration, structural changes
76
what are some mast cell cytokine suppressed by
glucocorticoids
77
endogenous inhibitors of mast cell activation
PGE2, adrenline, cortisol
78
pharmacological inhibitors of mast cell activation
disodium cromoglycate/ nedocromil sodium
79
what does disodium cromoglycate cause
reduction in mast cell degranulation, C-fibre activation and eosinophil activation
cause annexin-1 release (resolves inflammation)
80
omalizumab
humanised monoclonal antibody - inhibits mast cell activation - asthma
subcutaneous administration
81
omalizumab mechanism of action
binds to IgE and prevents binding to alpha chain of FceR1
| - IgE and FceR1 levels decrease (FceR1 dependent on ligand for maintained expression on cell surface)
82
glucocorticoids - what do they do
| what used in
reduce mast cell cytokine production
| asthma, hypersensitivity reactions (skin, eye, systemic anaphylaxis)
83
what do H1 R antagonists do
inhibit mediator actions
84
3 classes of H1R antagonists
1. sedative
2. non-sedative
3. newer non-sedative
85
sedative H1R antagonist
promethazin
86
non-sedative H1R antagonist
terfenadine
87
newer non-sedative H1R antagonist
loratidine
88
cysteinyl leukotriene R antagonists
montelukast
89
why cysLT-R antangonists
what used for
why
aspirin-induced and exercise induced asthma
| b/c subgroup overproduces LTs
90
asthma def
chronic inflammatory disorder of airways - airway hyperresponsiveness leading to symptoms
91
is asthma a single condition?
no - group of syndromes with same ending condition
92
pathology of asthma (what happens)
1. loss of epithelium - exposure of nerves - sensory signals to brain - ach onto smooth muscle
2. neuropeptides released - act on smooth muscle direclty
3. plasma leak from dilated vessels
4. angiogenesis
5. mucous hypersecretion
93
what is obstruction in asthma due to
1. smooth muscle shortening
2. bronchial wall oedema - swelling from engorgement of blood
3. mucous hypersecretion
94
airway smooth muscle shortening treated with
relievers, controllers, preventers
95
bronchial wall oedema and mucous hypersecretion treated with
preventers (b/c once occurs difficult to reverse pharmacologically
96
why alveoli more vunerable to collapse in asthma
scarring due to asthma - alveoli less able to inflate (b/c more inflated alveoli less likely to collapse)
97
what controls bronchoconstriction /dilation
circuating adrenaline on B2
98
contractile mechanism of smooth muscle
- increase intracellular Ca
- calcium binding to calmodulin
- activation of myosin light chain kinase
- phosphorylates myosin light chain
- cross bridges slide
99
mechanisms that increase free Ca
- V-G Ca channels
| - PLC - IP3
100
mechanisms decreasing free intracell Ca
- plasma Ca ATPase
| - sarcoplasmic reticulum Ca ATPase
101
asthma smooth muscle slower or faster recovery from LTs
slower
102
mediators that cause airway smooth muscle contraction
- Ach
- HA
- LTC4
- LTD4
103
mediators that cause airway smooth muscle relaxation
- PGE2
- adrenline
- PGI2
104
what 2 things block myosin light chain phosphatase
rho kinase
| protein kinase C
105
airway smooth muscle dysfunctions in asthma
- constriction
| - airway remodeling: proliferation, migration, secretion of cytokines, secretion of extracellular matrix proteins
106
what does airway smooth muscle secrete
- growth factors
- cytokines
- chemokines
- lipid mediators
- extracellular matrix components
107
change in what types of cells in asthma airways
- smooth muscle cell and goblet cell no. increase
- subepithelial collagen thickening
- infiltration of inflammatory cells - increase mucosal vascularity
- increase smooth muscle cell volume
108
how is viral replication different to bacterial replication
there's a long period where nothing happens - takes hours to see virus in cell (eclipse period) and even longer to see virus extracellularly (latent period)
109
why do viruses have eclipse periods
because at this stage there's no virus - only viral proteins and genes (because virus broken down into components so can start replicating)
110
stages of viral replication
```
1 attachment
2 penetration
3 uncoating
4a genome replication
4b RNA synthesis
4c protein synthesis
5 assembly
6 release
```
111
what defines and limits virus host species
the specific receptor on host cell membrane that viral attachment protein binds to
112
what receptor types can viruses attach (ie what are they made of)
protein
| carbohydrate
113
what specific virus uses two different host receptors and what are they
HIV
receptor - CD4
coreceptor - CCR5
114
process of HIV attachment
glycoprotein (gp41 and gp120) binds to CD4 (initial attachment)
- causes conformational change in gp
- gp can now recruit co-receptor CCR5 (close attachment)
115
two ways viruses penetrate
1 enveloped viruses - coat fuses with host cell membrane
| 2 enveloped and non-enveloped viruses - endocytosis
116
what does uncoating refer to
release of viral genome from protective capsid - enables nucleic acid to be transported within cell and transcribed
117
eg of virus that fuses with membrane and how
HIV
| hydrophobic region of gp41 is exposed on attachment - it initiates fusion of two membranes
118
eg of virus that is endocytosed
| why and how
togavirus
| host cell R is one in which binding causes endocytosis (normally for uptake of nutrients)
119
how does an endocytosed virus get out of endosome (2 ways)
1 low pH induces conformational change in viral proteins that exposes fusion region
2 lysis of endosome
120
in general where do DNA and RNA viruses replicate (exceptions?)
DNA - in nucleus
RNA - in cytoplasm
(exceptions - influenza and pox)
121
outline of replication of virus
messenger RNA produced and codes for viral proteins that are translated by host cell
122
early vs late proteins produced by viral replication
early - usually non-structural proteins (DNA or RNA polymerase)
late - structural (e.g. capsid proteins)
123
what is problem in host cell replication of RNA viruses
we don't have RNA dependent RNA polymerase
124
process of poliovirus (RNA virus) replication
- virus genome is linear single stranded plus sense RNA
- acts as mRNA - translated into one long protein = polyprotein
- polyprotein folds up and makes enzyme active site - cuts itself into individual proteins = auto-cleavage
- one of these proteins is RNA dependent RNA polymerase
- this starts making minus and more plus stranded RNA
125
what is different if virus was minus sense RNA
virus has to carry its own polymerase as a structural protein
126
what does virus have to have so it can replicate
has to produce mRNA from its genome
127
DNA viruses that have their own polymerases
pox
| hepadna
128
RNA viruses - which ones need to carry their own polymerase
```
negative stranded
(plus stranded encode their own polymerase so don't need to carry)
```
129
RNA virus exception - plus stranded that carries its own polymerase
retrovirus - RNA genome but converts to DNA with its own carried reverse transcriptase
130
translation of structural and non-structural proteins of viruses carried out by
ribosomes in host cell cytoplasm
131
post-translational cleavage of polyproteins or trimming of structural proteins usually needs...
virus-encoded proteases
132
where does glycosylation of envelope glycoproteins of viruses occur and what does it result in
RER and golgi vesicles, results in them being deposited on cell surface
133
all medically important viruses are enveloped or non-enveloped, and what shape
non enveloped
| icosahedral
134
two ways non-enveloped animal viruses assemble
1 spontaneous assembly
| 2 proteolytic cleavage to induce final conformation
135
how are non-enveloped viruses released
accumulate in cytoplasm or nucleus - only released when cell lyses
136
two ways enveloped viruses released
budding
| utilization of cellular secretory pathway
137
process of virus budding
- patches of viral envelope glycoproteins accumulate in plasma membrane
- capsid proteins and nucleic acid condense directly adjacent to cell membrane
- membrane surrounding nucleocaspid bulges out and becomes nipped off to form new enveloped virion
138
process of enveloped viruses using cellular secretory pathway
- virus particles endocytose into golgi-derived vesicles
| - released outside of cell when transport vesicle fuses with cell membrane
139
eg of virus that exits cell via cell secretory pathway
coronavirus
140
eg of virus that exits cell via budding
influenza
141
4 outcomes of viral infections
1 transformation to tumour cells
2 lytic infection
3 chronic infection
4 latent infection
142
inclusion bodies
accumulated viral proteins at site of virus assembly
143
what do most oncogenes code for
proteins with growth promoting properties - expression can lead to uncontrolled proliferation
144
where do virus encoded oncogenes come from
originally acquired from host - picked up during integration of virus genome into host DNA way back in evolution
145
viral genomes constantly changing as result of ...
1 mutation
2 recombination
3 reassortment
(2 and 3 if two viruses infect same cell)
146
why RNA viruses more prone to mutation
using own polymerase - doesn't have proofreading mechanisms our polymerases have
147
quasispecies
collection of slightly different viruses (as result of mutation)
148
virus reassortment
swapping of segments for viruses that have segmented genomes
149
4 ways infectious process of viruses can be stopped
1 antibody that blocks uptake and/or neutralises progeny virus
2 kill infected cell by cytotoxic T cells, NK cells or Ab-mediated mechanisms
3 interferon
4 block replication cycle with drugs
150
interferon
powerful cytokine released from infected cell - protects neighbouring cells from being infected
can synthetically produce - one of only broad spectrum anti-viral drugs we have (but toxic, lots of side effects)
151
acyclovir
guanosine analogue
incorporated into DNA and causes chain termination and cell death
(herpesvirus thymidine kinase needed so no effect of drug in normal cells)
152
does whether the disease is local or systemic impact on severity of disease
no
153
after initial acute infection, the course of infection is determined largely by...
the immune response of the hose (clearance or persistence of virus)
154
tropism
| and what initially determined by
= anatomical localization of infection
initially determined by receptor specificity of virus
155
through what cells do most viruses enter through, why
epithelial cells of mucosa
| b/c epidermis of skin covered by dying cells covered with keratin - hostile environment for viruses
156
in virus entry via respiratory tract, what determines initial site of virus deposition
droplet size: bigger - lodge in nose, smaller - alveoli
157
what are the barriers to infection in respiratory tract
mucous, cilia, alveolar macrophages, temperature gradient (URT 34, LRT 37 - e.g. some viruses replicate in 34 but not 37 - cant go down), IgA (particularly efficient at mucosal surfaces)
158
viruses of respiratory tract - remianing localised
- rhinovirus
- respiratory syncytial virus
- influenza
159
viruses of respiratory tract - spread systemically
- mumps, measles
- rubella virus
- varicella-zoster virus
160
viruses cause different syndromes in respiratory tract depending on...
where they infect in respiratory tree
161
common cause of URTI
rhinovirus
162
common cause of pharyngitis
adenovirus
163
common cause of croup
parainfluenza
164
common cause of bronchiolitis and pneumonia
RSV
165
what is histologically diagnostic of RSV
giant multinuclear cells - as virus replicating, puts gps on surface that bind to other cells and cause fusion
166
measles - what cells infect, what happens
diagnostic characteristic
measles virus infects local MACs lymphocytes and DCs - they then drain to lymph nodes and into circulation
koplick spots
167
entry of ingested viruses
swallowed or infect oropharynx thenbe carried elsewhere
168
barriers to infection of alimentary tract
- sequestration in intestinal contents
- mucous
- stomach acidity
- intestinal alkalinity
- proteolytic enzymes
- lipolytic activity of bile (bad for enveloped viruses)
- IgA
- scavenging Macs
169
characteristics of viruses that infect the intestinal tract
acid and bile resistant, non-enveloped
170
if viruses do not have receptors for epithelial cells, how do they enter
via breach in epithelial surface e.g. abrasions
171
how do many enteric viruses enter
via M cells ingesting them (they ingest antigens) and delivery to underlying lymphoid tissue by transcytosis
some kill M cells
172
how do rotaviruses survive transfer through gut, what do they do
they have a triple-shelled capsid
infect and destroy epithelial cells of intestinal villi and M cells causing inflammation and diarrhea
173
why do viruses cause diarrhoea
- absorption decreased by destruction of enterocytes
| - secretion of virus NSP4 protein from infected cells - increases fluid secretion of remaining intestinal cells
174
if viruses survive passage through gut, where can they replicate
peyer's patches - immune cells in groups in stomach
175
4 mechanisms of viral spread in the body
- local spread on epithelial surfaces
- subepithelial invasion and lymphatic spread
- spread via bloodstream - viremia
- neurla spread
176
e.g. of virus entering via conjunctiva
adenovirus
177
what is viruses barrier to bloodstream from epithelium
lymph node
178
how does virus overcome lymph node
has to hide from immune system, replicate v fast, or have lots of viruses
179
primary viremia
virus in blood
180
secondary viremia
virus replicating in enormous amounts in liver and spleen - then enters blood again
181
in viremia, do viruses free in plasma or cell-associated viruses persist for longer
-why
cell-associated
viruses free in plasma are vulnerable to immune attack - neutralised by Ab response and removed by macrophages
182
typical course of viremia
- invasion and multiplication - epitheial cells
- multiplication - regional lymph node
- primary viremia-bloodstream
- multiplication - liver and spleen (day 3)
- secondary viremia - blood stream
- focal infection - skin (all in 6 days)
183
how can viruses infect foetus
- cross placenta
- death and abortion by cytocidal viruses
- OR developental abnormalities by non-cytocidal viruses
184
how can baby be infected with virus at birth
- infected birth canal (varicella)
| - fecal contamination (coxsackie B)
185
viremia at birth can lead to
immunological tolerance - carriage state
186
what happens in congenital rubella syndrome
rubella slows down rate of cell division, baby small and development of key organs in first trimester is impaired
187
6 determinants of tropism
1 availability of R for virus
2 optimal temperature for replication
3 stability in pH extremes
4 ability to replicate in Macs and LYmphs
5 Polarized release (virus exiting apical surface less likely to infect deeper layers)
6 presence of activating enzymes
188
e.g. of how presence of activating enzymes required for viral tropism
influenza needs tryptase clara secreted by cells in large airways - so only in respiratory tract
189
2 mechanisms of disease production from viral infection
1 viral - induced damage
| 2 consequnces of immune response
190
4 ways virus can cause damage directly
1 death of cells directly from viral replication
2 death from toxicity of viral products
3 initiation of apoptosis
4 loss of function
191
consequences of immune response to viruses
immunopathology
immunosupression
autoimmunity
192
two types of antibody-mediated immunopathology in response to viral infection
1 antibody-dependent enhancement of infection by FcR-mediated uptake of virus-Ab complexes into cells (e.g. macs)
2 antigen-antibody complexes deposited in kidney - can cause glomerulonephritis and in blood vessel vasculitis
193
CD4 T cell mediated pathology in response to viral infection
- responsible for some viral rashes
| - bronchiolitis in infants with RSV
194
CD8 T cell mediated pathology in viral infection
- liver damage in Hep B
195
process of jaundice
- old RBCs destroyed by macs in spleen
- heme from hemoglobin converted to bilirubin (yellow)
- -> bloodstream --> liver for secretion in bile --> faeces
- damaged liver cells cannot carry out process - bilirubin in tissues
196
2 mechanisms of autoimmunity in viral infection
1 molecular mimicry - protein on virus raises Abs that also recognise self-antigens
2 polyclonal B cell activation by EBV
197
2 e.g.s of viruses that cause immunosuppression
HIV
| measles (temporary)
198
type 1 interferons:
- inhibits what
- activates what
- enhances expression of what
- produced by what
alpha and beta
- inhibits viral replication
- activates Nk cells
- enhances MHC class 1 expression
- produced by virus infected mac, DC and tissue cells
199
type 2 interferons
- inhibits what
- activates what
- enhances expression of what
- produced by what
gamma
- inhibits viral replication
- activates macs
- enhances MHC class I and II expression
- produced by NK cells (and T cells)
200
what 2 things activate NK cells
IL-12 and IFN-alpha/beta
201
two ways viruses evade immune attack
- not being recognised
| - interfere
202
which particular virus group has acquired many strategies for immune evasion
large complex DNA viruses- herpesviruses
203
antigenic variation in viruses
change in antigenic structure of virus due to selection of variant viruses that allow virus to escape neutralisation by pre-existing Ab
204
why does antigenic drift occur
due to error prone RNA dependent RNA polymerase
205
inhibiting T cell priming by DC
virus can block MHC interaction, costimulatory molecules
206
way that HIV evades CD8 T cell recognition
HIV encodes protein called Nef - induced endocytosis of MHC class I
207
how do HSV and CMV evade CD8 T cell recognition
bind to TAP transporter in ER (transports in viral proteins to be expressed on MHC) and prevents peptide translocation to ER
208
how does adenovirus evade CD8 T ell recognition
binds MHC and retains in ER
209
what are NK cells
distinct lineage of lymphocytes
show spontaneous cytotoxicity towards variety of tumour cells and virus-infected cells
-also major source of IFN-gamma
210
NK cells activated by
IL-12 or IFN-alpha/B
211
different NK clones have different ...
activation and inhibitory receptors
212
activation receptor of NK cells recognises...causes hwat
molecules on cell surface there as result of virus infection and send killing signal
213
inhibitory receptor of NK cells binds...
| causes what
```
MHC class I molecules on target cell
if engaged overrides killing signal
```
214
if class I is aberrantly expressed or absent on cell
inhibitor receptor of NK cells not engaged and NK cell kill target cell
215
viruses that reduce MHC class I on cells leaves them susceptible to
NK cell killing
216
when IFn engages with receptor what happens
100s genes turned on in cell - powerful response:
- upreguation of class I
- specific proteins with anti-viral activity upregulated (PKR)
217
how is PKR activated
has to auto-phosphorylate itself in presence of double stranded RNA (recognition domains hook over to bring terminal domains together)
218
action of PKR
binds to eIF2alpha, phosphyrolatees it and inactivates it - stops translation
219
3 ways viruses get around PKR
1 produce abundance of small double stranded RNAs - so small only one PKR can fit over - dilutes PKR
2 encode proteins that bind to and coat double stranded RNA so PKR cant bind
3 virus encodes homologue of eIF2, competes for PKR binding
220
genetic factors influencing susceptibility to viral infection
- inherited defects
- polyorphisms in genes controlling immune responses
- interferon-inducible genes (some might not have all able to be turned on)
- receptor gene deficiency
221
non-genetic factors influencing susceptibilityy to viral infection
- age (newborns and elderly more susceptible, but young suffer less from immunopathology)
- malnutrition
- hormones, pregnancy
- dual infections
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4 outcomes of viral infection
- fatal
- full recovery
- recovery but with permanent damage
- persistant infection
