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MD1 > Respiratory week 1 > Flashcards

Respiratory week 1 Flashcards

1
Q

allergy

A

immune-mediated inflammatory response to common environmental antigens that are otherwise harmless

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2
Q

atopy

A

genetic predisposition to allergy :

  • high levels of IgE
  • large numbers of eosinophils
  • large numbers of IL-4 secreting Th2 cells
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3
Q

allergen common features

A
  • repeated exposure via mucosal route
  • very stable
  • high solubility in bodily fluids
  • introduced in v low doses
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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

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5
Q

4 types of hypersensitivity

A

immediate hypersensitivity - Type 1

  • antibody mediated - TypeII
  • immune complex - Type III
  • delayed type hypersensitivity - Type IV
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6
Q

Type I hypersensitivity

A

immediate hypersensitivity IgE, mast cells and lipid mediators

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7
Q

Type II hypersensitivity

A

antibody mediated

IgM and IgG against cell-bound or extracellular matrix Ag

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8
Q

Type III hypersensitivity

A

immune complex - IgM and IgG immune complex deposition

complex can activate macrophages and inflammatory responses

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9
Q

Type IV hypersensitivity

A

delayed type - CD4 mediated

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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 `
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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
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12
Q

actions of histamine

A

vasodilation - swelling
sensitises nerve endings - itch
mucous hyperproduction - swelling

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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
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14
Q

hives sign you’re allergic?

A

no - can have hives without being allergic, but they are part of symptoms of allergic reaction

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15
Q

systemic hypersensitivity reaction

A

anaphylaxis - mast cell response in blood - increases circulating histamine - vasodilation everywhere - decrease MAP - decreased perfusion of organs

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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
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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
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18
Q

e.g of type IV hypersensitivity

A

tuberculin test - detects presence of Tbc-specific CD4 T cells

coeliac disease

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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

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20
Q

genetic disposition to coeliac disease

A

HLA-DQ2.5

this particular MHCII better at presenting transglutamase 2 in cleft due to shape

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21
Q

4 treatments of allergy

A
  1. adrenline (alaphylaxis, asthma)
  2. inhaled B-adrenoceptor ag (asthma)
  3. antihistamines (hives, allergic rhinitis)
  4. leukotriene R antagonists (allergic rhinitis, asthma)
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22
Q

corticosteroids

A

broad immunosuppression
- topical or systemic
suppress chronic inflammation by blocking gene transcription

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23
Q

disadvantages of corticosteroids

A

non-specific with side effects: osteoporosis, weight gain, Type II diabetes

  • effectiveness wanes over time
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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
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25
Q

immunotherapeutic treatments for allergic asthma

A
  • induce Treg - by desensitization
  • anti-IgE (antibody against IgE)
  • block IL-5 - skew response to Th1
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26
Q

airflow obstruction - what do you notice

A
  1. increased sensation of breathing
  2. increased respiratory muscle effort
  3. active exhalation
  4. longer time to inspire and expire
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27
Q

obstruction causes increase in load or drive

what does this lead to

A

load

leads to increase in work of breathing (WOB)

(anxiety causes increase in drive)

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28
Q

inspiration negative or positive pressure ventilation

A

negative

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29
Q

intrapleural pressure always intra-alveolar pressure

A
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30
Q

3 consequences of airway obstruction leading to increased WOB

A
  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
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31
Q

one important cause of ventilatory failure

Pa of O2 and CO2

A

respiratory (inspiratory) muscle fatigue

PaO2>60mmHg, PaCO2>50mmHg

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32
Q

exhalation active or passive?

when active?

A

normally passive

active - abdominals and internal intercostals - exercise/significant airflow obstruction

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33
Q

spirometry

A

measurement of forced expiratory volume vs time

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34
Q

airflow obstruction - what happens to FEV1 and FEV/FVC and FVC

A

reduced FEV1 and FEV1/FVC

same FVC, just takes longer

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35
Q

vital capacity

A

difference between TLC and residual volume

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36
Q

what happens if airflow obstruction causes uneven ventilation

A

get V/Q mismatch

ventilation becomes un-homogeneous, perfusion also un-homogeneous as compensatory mechanism (try to limit V/Q mismatch)

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37
Q

V/Q matching

A

ventilation/perfusion matching

=1 in all individual alveolar-capillary (A-C) units

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38
Q

low V/Q units

A

units that receive relatively less ventilation than perfusion

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39
Q

result of low V/Q units

A

oxygen binding sites may not be all filled - some blood returning to left atrium not fully oxygenated

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40
Q

2 ways of overcoming hypoxic effect of low V/Q

A

reduce blood flow

increase conc. of O in air

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41
Q

shunt

A

extreme form of low V/Q unit (V/Q=0)- no airflow at all, airway completely blocked

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42
Q

randomization

A

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

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43
Q

blinding

A

non-awareness of intervention allocation, with the aim to reduce information bias

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44
Q

intention to treat analysis

A

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

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45
Q

NNT=

A

1/(absolute risk or rate reduction)

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46
Q

systematic review

A

is a type of literature review that collects and critically analyzes multiple research studies or papers

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47
Q

meta-analysis

A

statistical aspect of a systematic review

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48
Q

PICOT parameters

A 
population
intervention
comparator
outcome
time
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49
Q

diagnstic test vs screening test

A

diagnostic - confirmation of disease or otherwise (clinical suspicion)
screening - identification of patients who may have disease (NO clinical suspicion)

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50
Q

sensitivity

A

% people with disease that test positive

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51
Q

specificity

A

% of people without disease that test negative

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52
Q

positive predictive value

A

% positive tests that are truly positive

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53
Q

negative predictive value

A

% negative tests that are truly negative

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54
Q

PPV and NPV are dependent on

A
  • sensitivity and specificity

- underlying prevalence of disease

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55
Q

PPV positively correlates with what

A

underlying prevalence of disease

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56
Q

likelihood ratio

A

likelihood that given test result would be expected in patient with the disease compared to patient without disease

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57
Q

main locations of mast cells

A

body sites in contact with external environment - skin, gut lung
- close to blood vessels/nerves/glands

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58
Q

external stimuli of mast cells

A

stings, allergen (IgE), polybasic drugs (morphine, vancomycin), mechanical stimulation, UV light/heat, osmotic stimuli - hypertonic saline

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59
Q

internal stimuli of mast cells

A

activated complement - c3a and c5a

neuropeptides(from sensory nerves)

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60
Q

allergen induced mast cell degranulation mechanism

A

cross linking of IgE bound FCeR1

(requires antigen-specific IgE produced in atopic subjects

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61
Q

transduction of IgE pathway in mast cells

A

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
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62
Q

immediate effects of mast cell activation

- time course

A
  • histamine
  • heparin
  • tryptase
  • TNFalpha
    30-45s
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63
Q

rapid effects of mast cell activation

-timecourse

A

cys-LTs
PGD2
10-30 mins

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64
Q

slow effects of mast cell activation

- timecourse

A 
IL-4
IL-5
GM-CSF
- T-cell adn eosinophil dependent reaction 
days
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65
Q

histamine actions on H1 receptors

A 
pain and itch
bronchconstriction
mucous secretion
vasodilation - hypotension
increase vascular leak - hypovolemia
CNS - wakefullness
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66
Q

histamine actions on H2

A

positive ionotropic and chronotropic

gastric acid secretion

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67
Q

what cells produce cysteinyl leukotrienes

A

eosinophils, mast cells, macrophages

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68
Q

cysteinyl leukotrienes made up of what, how

A

conjugation of glutathione with lipid

glutathion-S-transferase - LTC4 from LTA2

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69
Q

stimuli for cysteinyl leukotriene production

A

allergen, C5a, platelet activating factor (PAF)

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70
Q

where does LTC4 act

A

CysLT1

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71
Q

pathological roles of cysLTs

A

vasodilator in skeletal muscles, airway obstruction, nasal obstruction

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72
Q

why delay in cysLTs

A

PLA2 - has to de-esterify acy lipid stores

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73
Q

activity of cysLTs determined by what 3 factors

A
  1. amount of PLA2
  2. signal transduction - Ca/MAPK activity
  3. levels of inhibitors (annexin-1)
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74
Q

what is delayed and protracted release from mast cells

A

cytokines - ILs, TNF, chemokines, colony-stimulating factors

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75
Q

what does mast cell cytokine release cause

A

gene expression changes - inflammatory cell infiltration, structural changes

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76
Q

what are some mast cell cytokine suppressed by

A

glucocorticoids

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77
Q

endogenous inhibitors of mast cell activation

A

PGE2, adrenline, cortisol

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78
Q

pharmacological inhibitors of mast cell activation

A

disodium cromoglycate/ nedocromil sodium

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79
Q

what does disodium cromoglycate cause

A

reduction in mast cell degranulation, C-fibre activation and eosinophil activation
cause annexin-1 release (resolves inflammation)

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80
Q

omalizumab

A

humanised monoclonal antibody - inhibits mast cell activation - asthma
subcutaneous administration

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81
Q

omalizumab mechanism of action

A

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)

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82
Q

glucocorticoids - what do they do

what used in

A

reduce mast cell cytokine production

asthma, hypersensitivity reactions (skin, eye, systemic anaphylaxis)

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83
Q

what do H1 R antagonists do

A

inhibit mediator actions

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84
Q

3 classes of H1R antagonists

A
  1. sedative
  2. non-sedative
  3. newer non-sedative
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85
Q

sedative H1R antagonist

A

promethazin

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86
Q

non-sedative H1R antagonist

A

terfenadine

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87
Q

newer non-sedative H1R antagonist

A

loratidine

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88
Q

cysteinyl leukotriene R antagonists

A

montelukast

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89
Q

why cysLT-R antangonists
what used for
why

A

aspirin-induced and exercise induced asthma

b/c subgroup overproduces LTs

90
Q

asthma def

A

chronic inflammatory disorder of airways - airway hyperresponsiveness leading to symptoms

91
Q

is asthma a single condition?

A

no - group of syndromes with same ending condition

92
Q

pathology of asthma (what happens)

A
  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
Q

what is obstruction in asthma due to

A
  1. smooth muscle shortening
  2. bronchial wall oedema - swelling from engorgement of blood
  3. mucous hypersecretion
94
Q

airway smooth muscle shortening treated with

A

relievers, controllers, preventers

95
Q

bronchial wall oedema and mucous hypersecretion treated with

A

preventers (b/c once occurs difficult to reverse pharmacologically

96
Q

why alveoli more vunerable to collapse in asthma

A

scarring due to asthma - alveoli less able to inflate (b/c more inflated alveoli less likely to collapse)

97
Q

what controls bronchoconstriction /dilation

A

circuating adrenaline on B2

98
Q

contractile mechanism of smooth muscle

A
  • increase intracellular Ca
  • calcium binding to calmodulin
  • activation of myosin light chain kinase
  • phosphorylates myosin light chain
  • cross bridges slide
99
Q

mechanisms that increase free Ca

A
  • V-G Ca channels

- PLC - IP3

100
Q

mechanisms decreasing free intracell Ca

A
  • plasma Ca ATPase

- sarcoplasmic reticulum Ca ATPase

101
Q

asthma smooth muscle slower or faster recovery from LTs

A

slower

102
Q

mediators that cause airway smooth muscle contraction

A
  • Ach
  • HA
  • LTC4
  • LTD4
103
Q

mediators that cause airway smooth muscle relaxation

A
  • PGE2
  • adrenline
  • PGI2
104
Q

what 2 things block myosin light chain phosphatase

A

rho kinase

protein kinase C

105
Q

airway smooth muscle dysfunctions in asthma

A
  • constriction

- airway remodeling: proliferation, migration, secretion of cytokines, secretion of extracellular matrix proteins

106
Q

what does airway smooth muscle secrete

A
  • growth factors
  • cytokines
  • chemokines
  • lipid mediators
  • extracellular matrix components
107
Q

change in what types of cells in asthma airways

A
  • smooth muscle cell and goblet cell no. increase
  • subepithelial collagen thickening
  • infiltration of inflammatory cells - increase mucosal vascularity
  • increase smooth muscle cell volume
108
Q

how is viral replication different to bacterial replication

A

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
Q

why do viruses have eclipse periods

A

because at this stage there’s no virus - only viral proteins and genes (because virus broken down into components so can start replicating)

110
Q

stages of viral replication

A 
1 attachment 
2 penetration
3 uncoating
4a genome replication
4b RNA synthesis
4c protein synthesis
5 assembly
6 release
111
Q

what defines and limits virus host species

A

the specific receptor on host cell membrane that viral attachment protein binds to

112
Q

what receptor types can viruses attach (ie what are they made of)

A

protein

carbohydrate

113
Q

what specific virus uses two different host receptors and what are they

A

HIV
receptor - CD4
coreceptor - CCR5

114
Q

process of HIV attachment

A

glycoprotein (gp41 and gp120) binds to CD4 (initial attachment)

  • causes conformational change in gp
  • gp can now recruit co-receptor CCR5 (close attachment)
115
Q

two ways viruses penetrate

A

1 enveloped viruses - coat fuses with host cell membrane

2 enveloped and non-enveloped viruses - endocytosis

116
Q

what does uncoating refer to

A

release of viral genome from protective capsid - enables nucleic acid to be transported within cell and transcribed

117
Q

eg of virus that fuses with membrane and how

A

HIV

hydrophobic region of gp41 is exposed on attachment - it initiates fusion of two membranes

118
Q

eg of virus that is endocytosed

why and how

A

togavirus

host cell R is one in which binding causes endocytosis (normally for uptake of nutrients)

119
Q

how does an endocytosed virus get out of endosome (2 ways)

A

1 low pH induces conformational change in viral proteins that exposes fusion region
2 lysis of endosome

120
Q

in general where do DNA and RNA viruses replicate (exceptions?)

A

DNA - in nucleus
RNA - in cytoplasm
(exceptions - influenza and pox)

121
Q

outline of replication of virus

A

messenger RNA produced and codes for viral proteins that are translated by host cell

122
Q

early vs late proteins produced by viral replication

A

early - usually non-structural proteins (DNA or RNA polymerase)
late - structural (e.g. capsid proteins)

123
Q

what is problem in host cell replication of RNA viruses

A

we don’t have RNA dependent RNA polymerase

124
Q

process of poliovirus (RNA virus) replication

A
  • 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
Q

what is different if virus was minus sense RNA

A

virus has to carry its own polymerase as a structural protein

126
Q

what does virus have to have so it can replicate

A

has to produce mRNA from its genome

127
Q

DNA viruses that have their own polymerases

A

pox

hepadna

128
Q

RNA viruses - which ones need to carry their own polymerase

A 
negative stranded 
(plus stranded encode their own polymerase so don't need to carry)
129
Q

RNA virus exception - plus stranded that carries its own polymerase

A

retrovirus - RNA genome but converts to DNA with its own carried reverse transcriptase

130
Q

translation of structural and non-structural proteins of viruses carried out by

A

ribosomes in host cell cytoplasm

131
Q

post-translational cleavage of polyproteins or trimming of structural proteins usually needs…

A

virus-encoded proteases

132
Q

where does glycosylation of envelope glycoproteins of viruses occur and what does it result in

A

RER and golgi vesicles, results in them being deposited on cell surface

133
Q

all medically important viruses are enveloped or non-enveloped, and what shape

A

non enveloped

icosahedral

134
Q

two ways non-enveloped animal viruses assemble

A

1 spontaneous assembly

2 proteolytic cleavage to induce final conformation

135
Q

how are non-enveloped viruses released

A

accumulate in cytoplasm or nucleus - only released when cell lyses

136
Q

two ways enveloped viruses released

A

budding

utilization of cellular secretory pathway

137
Q

process of virus budding

A
  • 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
Q

process of enveloped viruses using cellular secretory pathway

A
  • virus particles endocytose into golgi-derived vesicles

- released outside of cell when transport vesicle fuses with cell membrane

139
Q

eg of virus that exits cell via cell secretory pathway

A

coronavirus

140
Q

eg of virus that exits cell via budding

A

influenza

141
Q

4 outcomes of viral infections

A

1 transformation to tumour cells
2 lytic infection
3 chronic infection
4 latent infection

142
Q

inclusion bodies

A

accumulated viral proteins at site of virus assembly

143
Q

what do most oncogenes code for

A

proteins with growth promoting properties - expression can lead to uncontrolled proliferation

144
Q

where do virus encoded oncogenes come from

A

originally acquired from host - picked up during integration of virus genome into host DNA way back in evolution

145
Q

viral genomes constantly changing as result of …

A

1 mutation
2 recombination
3 reassortment
(2 and 3 if two viruses infect same cell)

146
Q

why RNA viruses more prone to mutation

A

using own polymerase - doesn’t have proofreading mechanisms our polymerases have

147
Q

quasispecies

A

collection of slightly different viruses (as result of mutation)

148
Q

virus reassortment

A

swapping of segments for viruses that have segmented genomes

149
Q

4 ways infectious process of viruses can be stopped

A

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
Q

interferon

A

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
Q

acyclovir

A

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
Q

does whether the disease is local or systemic impact on severity of disease

A

no

153
Q

after initial acute infection, the course of infection is determined largely by…

A

the immune response of the hose (clearance or persistence of virus)

154
Q

tropism

and what initially determined by

A

= anatomical localization of infection

initially determined by receptor specificity of virus

155
Q

through what cells do most viruses enter through, why

A

epithelial cells of mucosa

b/c epidermis of skin covered by dying cells covered with keratin - hostile environment for viruses

156
Q

in virus entry via respiratory tract, what determines initial site of virus deposition

A

droplet size: bigger - lodge in nose, smaller - alveoli

157
Q

what are the barriers to infection in respiratory tract

A

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
Q

viruses of respiratory tract - remianing localised

A
  • rhinovirus
  • respiratory syncytial virus
  • influenza
159
Q

viruses of respiratory tract - spread systemically

A
  • mumps, measles
  • rubella virus
  • varicella-zoster virus
160
Q

viruses cause different syndromes in respiratory tract depending on…

A

where they infect in respiratory tree

161
Q

common cause of URTI

A

rhinovirus

162
Q

common cause of pharyngitis

A

adenovirus

163
Q

common cause of croup

A

parainfluenza

164
Q

common cause of bronchiolitis and pneumonia

A

RSV

165
Q

what is histologically diagnostic of RSV

A

giant multinuclear cells - as virus replicating, puts gps on surface that bind to other cells and cause fusion

166
Q

measles - what cells infect, what happens

diagnostic characteristic

A

measles virus infects local MACs lymphocytes and DCs - they then drain to lymph nodes and into circulation

koplick spots

167
Q

entry of ingested viruses

A

swallowed or infect oropharynx thenbe carried elsewhere

168
Q

barriers to infection of alimentary tract

A
  • sequestration in intestinal contents
  • mucous
  • stomach acidity
  • intestinal alkalinity
  • proteolytic enzymes
  • lipolytic activity of bile (bad for enveloped viruses)
  • IgA
  • scavenging Macs
169
Q

characteristics of viruses that infect the intestinal tract

A

acid and bile resistant, non-enveloped

170
Q

if viruses do not have receptors for epithelial cells, how do they enter

A

via breach in epithelial surface e.g. abrasions

171
Q

how do many enteric viruses enter

A

via M cells ingesting them (they ingest antigens) and delivery to underlying lymphoid tissue by transcytosis

some kill M cells

172
Q

how do rotaviruses survive transfer through gut, what do they do

A

they have a triple-shelled capsid

infect and destroy epithelial cells of intestinal villi and M cells causing inflammation and diarrhea

173
Q

why do viruses cause diarrhoea

A
  • absorption decreased by destruction of enterocytes

- secretion of virus NSP4 protein from infected cells - increases fluid secretion of remaining intestinal cells

174
Q

if viruses survive passage through gut, where can they replicate

A

peyer’s patches - immune cells in groups in stomach

175
Q

4 mechanisms of viral spread in the body

A
  • local spread on epithelial surfaces
  • subepithelial invasion and lymphatic spread
  • spread via bloodstream - viremia
  • neurla spread
176
Q

e.g. of virus entering via conjunctiva

A

adenovirus

177
Q

what is viruses barrier to bloodstream from epithelium

A

lymph node

178
Q

how does virus overcome lymph node

A

has to hide from immune system, replicate v fast, or have lots of viruses

179
Q

primary viremia

A

virus in blood

180
Q

secondary viremia

A

virus replicating in enormous amounts in liver and spleen - then enters blood again

181
Q

in viremia, do viruses free in plasma or cell-associated viruses persist for longer
-why

A

cell-associated

viruses free in plasma are vulnerable to immune attack - neutralised by Ab response and removed by macrophages

182
Q

typical course of viremia

A
  • 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
Q

how can viruses infect foetus

A
  • cross placenta
  • death and abortion by cytocidal viruses
  • OR developental abnormalities by non-cytocidal viruses
184
Q

how can baby be infected with virus at birth

A
  • infected birth canal (varicella)

- fecal contamination (coxsackie B)

185
Q

viremia at birth can lead to

A

immunological tolerance - carriage state

186
Q

what happens in congenital rubella syndrome

A

rubella slows down rate of cell division, baby small and development of key organs in first trimester is impaired

187
Q

6 determinants of tropism

A

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
Q

e.g. of how presence of activating enzymes required for viral tropism

A

influenza needs tryptase clara secreted by cells in large airways - so only in respiratory tract

189
Q

2 mechanisms of disease production from viral infection

A

1 viral - induced damage

2 consequnces of immune response

190
Q

4 ways virus can cause damage directly

A

1 death of cells directly from viral replication
2 death from toxicity of viral products
3 initiation of apoptosis
4 loss of function

191
Q

consequences of immune response to viruses

A

immunopathology
immunosupression
autoimmunity

192
Q

two types of antibody-mediated immunopathology in response to viral infection

A

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
Q

CD4 T cell mediated pathology in response to viral infection

A
  • responsible for some viral rashes

- bronchiolitis in infants with RSV

194
Q

CD8 T cell mediated pathology in viral infection

A
  • liver damage in Hep B
195
Q

process of jaundice

A
  • 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
Q

2 mechanisms of autoimmunity in viral infection

A

1 molecular mimicry - protein on virus raises Abs that also recognise self-antigens
2 polyclonal B cell activation by EBV

197
Q

2 e.g.s of viruses that cause immunosuppression

A

HIV

measles (temporary)

198
Q

type 1 interferons:

  • inhibits what
  • activates what
  • enhances expression of what
  • produced by what
A

alpha and beta

  • inhibits viral replication
  • activates Nk cells
  • enhances MHC class 1 expression
  • produced by virus infected mac, DC and tissue cells
199
Q

type 2 interferons

  • inhibits what
  • activates what
  • enhances expression of what
  • produced by what
A

gamma

  • inhibits viral replication
  • activates macs
  • enhances MHC class I and II expression
  • produced by NK cells (and T cells)
200
Q

what 2 things activate NK cells

A

IL-12 and IFN-alpha/beta

201
Q

two ways viruses evade immune attack

A
  • not being recognised

- interfere

202
Q

which particular virus group has acquired many strategies for immune evasion

A

large complex DNA viruses- herpesviruses

203
Q

antigenic variation in viruses

A

change in antigenic structure of virus due to selection of variant viruses that allow virus to escape neutralisation by pre-existing Ab

204
Q

why does antigenic drift occur

A

due to error prone RNA dependent RNA polymerase

205
Q

inhibiting T cell priming by DC

A

virus can block MHC interaction, costimulatory molecules

206
Q

way that HIV evades CD8 T cell recognition

A

HIV encodes protein called Nef - induced endocytosis of MHC class I

207
Q

how do HSV and CMV evade CD8 T cell recognition

A

bind to TAP transporter in ER (transports in viral proteins to be expressed on MHC) and prevents peptide translocation to ER

208
Q

how does adenovirus evade CD8 T ell recognition

A

binds MHC and retains in ER

209
Q

what are NK cells

A

distinct lineage of lymphocytes
show spontaneous cytotoxicity towards variety of tumour cells and virus-infected cells
-also major source of IFN-gamma

210
Q

NK cells activated by

A

IL-12 or IFN-alpha/B

211
Q

different NK clones have different …

A

activation and inhibitory receptors

212
Q

activation receptor of NK cells recognises…causes hwat

A

molecules on cell surface there as result of virus infection and send killing signal

213
Q

inhibitory receptor of NK cells binds…

causes what

A 
MHC class I molecules on target cell
if engaged overrides killing signal
214
Q

if class I is aberrantly expressed or absent on cell

A

inhibitor receptor of NK cells not engaged and NK cell kill target cell

215
Q

viruses that reduce MHC class I on cells leaves them susceptible to

A

NK cell killing

216
Q

when IFn engages with receptor what happens

A

100s genes turned on in cell - powerful response:

  • upreguation of class I
  • specific proteins with anti-viral activity upregulated (PKR)
217
Q

how is PKR activated

A

has to auto-phosphorylate itself in presence of double stranded RNA (recognition domains hook over to bring terminal domains together)

218
Q

action of PKR

A

binds to eIF2alpha, phosphyrolatees it and inactivates it - stops translation

219
Q

3 ways viruses get around PKR

A

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
Q

genetic factors influencing susceptibility to viral infection

A
  • 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
Q

non-genetic factors influencing susceptibilityy to viral infection

A
  • age (newborns and elderly more susceptible, but young suffer less from immunopathology)
  • malnutrition
  • hormones, pregnancy
  • dual infections
222
Q

4 outcomes of viral infection

A
  • fatal
  • full recovery
  • recovery but with permanent damage
  • persistant infection

MD1 (5 decks)

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