week 6 Flashcards
1
Q
who is Edward Jenson ?
A
man responsible for creating vaccination science- exposure to cow pox- leading to immunity from small pox
2
Q
describe innate immunity (exam q) (5)
A
- early phase of host response- first line
- present in all individuals at all times
- does not increase with repeated exposure
- can discriminate between groups of pathogens
- predates separation of animal and plant lineage
3
Q
describe adaptive immunity (exam q) (5)
A
- generated by specific lymphocytes (B and T cells)
- can discriminate between individual pathogens
- associated with ‘memory’
- response gets better(more aggressive) and faster with each exposure
- appears abruptly in evolution
4
Q
where do all cellular elements of blood- including immune cells arise from?
A
pluripotent hematopoietic stem cells
5
Q
do B cells and T cells come from lymphoid or myeloid lineage ?
A
lymphoid
6
Q
do macrophages come from lymphoid or myeloid lineage ?
A
myeloid
7
Q
do neutrophils and eosinophils come from lymphoid or myeloid lineage ?
A
myeloid
8
Q
if the atomic barrier fails- what is the next line of defence?
A
complement/ antimicrobial proteins
9
Q
if complement/ antimicrobial proteins fail, what is the next line of defence?
A
innate immune cells
10
Q
if innate immune cells fail- what is the next line of defence?
A
adaptive immunity
11
Q
give 2 examples of innate immune cells?
A
macrophages and natural killer cells
12
Q
name one example of an antimicrobial protein
A
defensins
13
Q
name 3 examples of an atomic barrier
A
skin
oral mucosa
respiratory epithelium
intestine
14
Q
name 2 examples of cells involved in adaptive immunity
A
b cells
antibodies
T cells
15
Q
name 3 sensor cells
A
macrophages
neutrophils
dendritic cells
16
Q
what kind of cell is associated with: phagocytosis and activation of bactericidal mechanisms, antigen presentation?
A
macrophages
17
Q
what kind of cell is associated with: killing of antibody coated parasites?
A
eosinophil
18
Q
what kind of cell is associated with: antigen uptake in peripheral sites, antigen presentation?
A
dendritic cell
19
Q
what kind of cell is associated with: promotion allergic responses and augmentation of anti-parasitic immunity?
A
basophil
20
Q
what kind of cell is associated with: phagocytosis and activation of bactericidal mechanisms?
A
neutrophil
21
Q
what kind of cell is associated with: release of granules containing histamine and active agents?
A
mast cell
22
Q
which of innate and adaptive immunity is more specific?
A
adaptive
23
Q
what is the different between b cells and macrophages in terms of receptors?
A
b cells have one highly specific receptor whereas macrophages have many receptors that cover a broad range
24
Q
bacteria trigger macrophages to release what 2 things?
A
cytokines and chemokines
25
which region of the antibody will bind to the antigen?
variable
26
what region of the antibody can bind to macrophages?
constant region
27
why are epitopes important?
they are very shape dependent- if they are denatured or damaged and their shape is changed the antibody cannot bind to the antigen
28
what cell recognises the epitopes- even if they are buried inside an antigen
T cells
29
do T cells or antibodies recognise shape?
antibody
30
do T cells or antibodies recognise linear peptides?
T cells
31
how do dendritic cells initiate adaptive immune responses?
up-take antigen in the tissues and stimulate naive T lymphocyte activation, proliferation and differentiation
32
why are dendritic cells important in adaptive immunity?
specialised to ingest a wide range of pathogens and then express co-stimulatory molecules that support T cell proliferation and differentiation
33
name 4 non specific asthma stimuli
exercise
cold air
hyperventilation
chemical agents
34
name 2 different specific asthma stimuli
allergens
aspirin
35
name 5 characteristics of asthma (internally)
- inflammation
- hyper-responsiveness of smooth muscle to substances that cause contraction of smooth muscle
- hypo-responsiveness of the smooth muscle to substances that relax smooth muscle
- neuronal imbalance
- hyperplasia (more of) and hypertrophy (bigger) airway smooth muscle
36
name 3 morphologic changes in bronchial asthma
- lungs are over distended (due to over inflation)
- small areas of atelectasis can be seen( dead tissue, coming away from lining- lack of oxygen)
- occlusion of bronchi and bronchioles by thick tenacious mucous plug
37
name 2 cell types that are a marker of asthma when present in airway lumen
eosinophils and macrophages
38
name 6 structural (remodelling) changes in asthma
- epithelial damage
- mucosal oedema- more mucous
- increased intraluminal secretions
- basement membrane thickening
- smooth muscle hypertrophy and hyperplasia
- inflammation
39
describe how smooth muscle behaves differently in asthma
inflammation causes white blood cells present in lumen release inflammatory meditators which increase mediator and cytokine induced contraction
alteration in calcium control - causes changes in contraction and relaxation
proliferative response increases muscle mass and force of contraction
more contraction due to cytokines present in smooth muscle (hyper-responsive)
40
name 2 chemical changes as a result of asthma
- higher amounts of Rho kinase - due to cytokine mediated gene induction -causes more sustained calcium contraction even when calcium returns to basal level
- higher levels of M3 receptors- causes smooth muscle contraction and mucous secretion
41
name an example of an inflammatory mediator that can modulate adrenergic control
histamine
42
name 4 defects in cholinergic innervation associated with asthma
- increased vagal tone
- reflex bronchoconstriction
- increased Ach released
- increase post synaptic muscarinic receptor function
43
how do C fibres cause bronchoconstriction?
afferent nerves eg C fibres respond to histamine, bradykinin, prostaglandins etc to cause reflex bronchoconstriction
44
what does NANC stand for?
non adrenergic non cholinergic
45
give an example of a substance which causes NANC inhibition, does this cause relaxation or constriction?
nitric oxide
causes relaxation
46
give an 2 example of a substance which causes NANC excitation, does this cause relaxation or constriction?
substance P/ neurokinins
prostaglandins, bradykinin
causes constriction
47
describe the nature of seasonal rhinitis
symptomatic disorder - caused by exposure to allergens (pollen) via IgE mediated hypersensitivity reactions
Dendritic cells process allergens and present their peptides on the major histocompatibility complex (MHC)
Differentiation of naïve CD4 T cells to allergen specific Th2 cell- activated Th2 cells such as mast cells secrete histamine causing hey fever symptoms
48
name 3 treatment for allergic rhinitis
first line
- oral antihistamine
- intranasal antihistamine
second line
- leukotriene receptor antagonist
49
which sections of the skin are affected by eczema ?
epidermis and dermis
50
what is involved in the genetic predisposition to atopic dermatitis ?
a genetic predisposition to produce an exaggerated IgE mediated hypersensitivity reaction in response to harmless allergens
51
name 5 possible treatments for atopic dermatitis
- emollient's
- topical corticosteroids
- oral antibiotics therapy
- antihistamine
- light therapy (for chronic)
52
name 3 possible treatment for angio-oedema without airway involvement
- trigger identification and avoidance (ie stop drug)
- antihistamine
- systemic corticosteroids
53
name 4 possible treatment for angio-oedema with airway involvement
- trigger identification and avoidance
- adrenaline and airway protection
- antihistamine
- IV systemic corticosteroids
54
name 3 treatments for mild psoriasis
- topical corticosteroid
- topical vitamin D analogue
- topical coal tar
55
name 3 treatments for moderate- severe psoriasis
- methotrexate
- oral retinoid
- ciclosporin
56
describe the underlying immunology for psoriasis
damaged keratinocytes during exposure to microbial or mechanical injury - activates macrophages and dermal dendritic cells which are antigen presenting cells (APC)
APC interact with T cells which produce a pro inflammatory cytokine
57
describe the mechanism behind a hypersensitive reaction
histamine is released when the trigger/ allergen causes B cells to activate and form plasma cells which then form IgE antibodies- which attach to mast cells
mast cells then activate- releasing granules containing histamine
58
state the 5 steps of an accuracy checking SOP
1- check patient details and bag label
2- check drug name, formulation, on Rx, product and label
3- check strength, dose, instructions on Rx, product and label
4- check quantity, expiry and PIL is inside
5- check pharmacy details, date dispensed, warning
59
what is the acceptable error rate in accuracy checking?
0.02%
2 in 10,000 items
60
name 5 different cell types involved in asthma
mast cells
neutrophils
basophils
macrophages
eosinophils
61
how are mast cells involved in asthma ?
these cells respond to allergen and IgE by releasing histamine and various interleukins like IL1
62
how are macrophages involved in asthma?
these cells release prostanoids, cytokines and leukotrienes
63
how are eosinophils involved in asthma
these cells release PAF, CSF which causes haematopoetic stem cells to differentiate into progenitor cells , GMSCF- which causes progenitor cells to differentiate into eosinophils
64
why do NSAIDs not work in asthma?
NSAIDs reduce PGE2 and PGF2a in the lung
may also redirect activation of the leukotriene pathway which is contractile
65
how do antihistamines not work in asthma?
even though mast cells product histamine- it is not so important in airway smooth muscle contraction in humans- works well in guinea pigs
66
name 2 B2 adrenoceptor agonists
salbutamol
salmeterol
67
which chemical functional group on salbutamol improves its selectivity ?
tertiary butyl group
68
describe salbutamol and salmeterols MOA
- inactivates MLCK (myosin light-chain kinase)
- protein kinase A may inactivate ins (1,4,5) P3 receptors so that less calcium is released- inhibting contraction
- calcium efflux pump (which reduces calcium levels) is increased by protein kinase A
- this inactivates Raf-1 kinase which inhibits proliferation
69
describe how salbutamol and salmeterol are different- how do they work differently?
salbutamol= short acting
salmeterol= long acting
salmeterol has lipophilic groups attached to it which interact with eco-sites on the receptor- this locks the ligand onto the receptor binding site- hence long acting
70
is salbutamol or salmeterol more potent- how much more? why is this?
salmeterol - about 1000x more potent
binds for longer and more strongly at the receptor
71
how do salbutamol and salmeterol use acetylcholine to affect smooth muscle ?
they inhibit its release- since it is an excitatory neurotransmitter it would constrict smooth muscle in the airway
72
why is it useful that salbutamol and salmeterol can reduce vascular permeability ?
this stops there being too much fluid in the lungs which is particularly bad in asthmatic patients
73
name the 3 mechanisms responsible for de- sensitisation
- Phosphorylation of the occupied receptor by a specific receptor kinase, termed b-adrenoceptor kinase (b-ARK)
- Internalisation of the receptor.(to take receptor into the cell, no receptor to activate anymore)
- Phosphorylation of the occupied receptor by protein kinase A; e.g. negative feedback
74
why is there less de sensitisation to salmeterol compared to salbutamol?
it is a partial agonist
therefore less phosphorylation of receptor and less internalisation of receptor
75
name 3 issues with systemic delivery of salbutamol and salmeterol
- increased blood flow- decrease in BP
- increased glucose, fatty acids, ketones
- increase in tremor in skeletal muscle
76
explain how glucocorticoids work in asthma
- dampen inflammatory responses
- interacts with intracellular receptor- steroid binds to receptor- mediates transcription of anti inflammatory genes, transcribes new b2 adrenoceptors- negative effects on pro inflammatory genes
77
describe what is meant by synergy between salbutamol and steroids in asthma treatment
- work on 2 different pathways to do similar things- working together
ie steroids increase beta 2 receptor expression where salbutamol increases glucocorticoid receptor half life
why good- can use less of each drug- less side effects
78
name a leukotriene inhibitor
montelukast
79
name 3 things leukotrienes do that contributes to asthma symptoms
promote WBC in the area
causes constriction of airways
promotes inflammation
80
name the pathway the leukotriene inhibitors act on
5 lipooxygenase pathway
81
name 4 positive effects of theophylline in asthma
- smooth muscle relaxation
- inhibit anaphylactic release of mediators
- suppress oedema
- central stimulation of ventilation
82
name 5 problems with using theophylline in asthma
- side effects- anorexia, vomiting
- non selective
- dose needs to be low to avoid gI problems
- CNS stimulation the maintenance dose is increased too quickly
- serious toxicity can cause seizures
83
why are antibodies a last resort treatment in asthma
- very expensive
84
how does antibody therapy work in asthma treatment ?
targets cytokine- gets rid of it
85
what is spirometry used to diagnose?
airflow obstructions in patients with respiratory symptoms
also used to monitor progression, rehabilitation and treatment gains
86
name 7 factors which can affect FEV1, FVC and/ or PEFR
gender
age
ace/ ethnicity
pollution exposure
smoking status
exercise
body weight
87
what is the maximal amount of air exhaled steadily from full inspiration to maximal expiration described as?
slow vital capacity
88
what is the volume of lungs form full inspiration to forced maximal expiration described as?
forced vital capacity
89
what is the volume of air expelled in the first second of a forced expiration described as?
forced expiratory volume in one second
90
why is FEV1 good in COPD (5 reasons)?
- reproducible and objective
- well defined reference ranges
- quick and easy at all stages of disease
- serial measurements can show disease progression
91
why is peak flow not used in disease diagnosis?
cannot distinguish between obstruction and restriction of airway
92
when is FER reduced?
in obstructive disease
93
describe FVC in stage one COPD
mild- 80% or above FVC
94
describe FVC in stage two COPD
moderate 50-79%
95
describe FVC in stage three COPD
severe 30-49%
96
describe FVC in stage four COPD
very severe below 30%
97
when is reversibility testing used?
to distinguish between asthma and COPD
98
what is reversibility testing?
- baseline spirometry
- bronchodilator (salbutamol) given
- repeat spirometry test- increase of >400ml from baseline in FEV1 in suggestive of asthma
99
productive cough? COPD? asthma? which is more likely ?
COPD
asthma tends to be dry cough
100
which is more likely to cause sleep disturbances due to waking up breathless and wheezing, COPD or asthma?why?
asthma
COPD symptoms are constant- don't change for time of day
asthma tends to get worse in the evening through to early morning- most asthma attacks are at 2-4 am
101
how can methotrexate/ sulfasalazine affect COPD/asthma?
can cause interstitial pulmonary fibrosis- which is thickening of the lung tissue and thus losing elasticity- resulting in restriction of the pulmonary bed
102
how do epithelial cells interfere with infection?
- secrete mucous- interferes with adhesion of pathogens and results in expulsion resulting from beating of cilia
- produce antimicrobial peptides such as B-defensins that damage bacterial cells membranes and surfactant proteins A and D that facilitate phagocytosis
103
infectious agents induce inflammatory response by activating which kind of immunity?
innate
104
epithelium penetration by infectious agents results in what ?
recognition of pathogen surface molecules by macrophages and subsequent phagocytosis
105
activated macrophages secrete 2 chemicals, what are they and what do they do?
cytokines- affect behaviour of other cells
chemokine- attract other cells
therefore these 2 cell types initiate inflammation
106
how do infectious agents induce adaptive immunity?
by activating DCs (dendritic cells)
107
how do dendritic cells induce adaptive immunity?
DCs ingest pathogens in infected tissues
this is dependent on pathogen recognition receptors on macropinocytosis
DCs mature and migrate to peripheral lymphoid organs and present pathogen antigens to T cells which become activated and contribute to adaptive immunity
108
epithelial cells can be activated directly by molecules such as - by what receptors?
molecules such as allergens
by receptors such as pattern recognition receptors or protease activated receptors
109
how do allergenic proteases decrease barrier function?
by cleaving epithelial cell tight junction proteins
110
name 2 cytokines produced by epithelial cells
IL-25
IL-33
111
what can IL-25 and IL-33 cause?
cause migration and activation of DCs to induce T cell immune responses
112
what are DCs necessary for inducing?
Th2 responses
113
how do DCs promote Th2 differentiation?
DCs migrate regional lymph nodes and mature into cells that favour Th2 differentiation
114
what does IL-4 promote ?
IgE production in B cells
115
what does IL-5 promote?
drives eosinophil recruitment in lung tissue
116
what does IL-13 promote?
causes bronchial hyper-reactivity
117
how are ILC2s activated?
by IL-25 and IL-33
118
what are ILC2s? when are they produced?
type of lymphoid cell
produced in response to injury or PAMPS
119
ILCs secrete large amounts of what? and small amounts of what?
large- IL-5, IL-3
small- IL-4
120
what do eosinophils synthesis? why do they do this?
mediators such as cytokines and leukotrienes- do this to amplify inflammatory response
121
what does eosinophil peroxides do?
cause bronchial- hyper- reactivity and activation of DCs to drive Th2 polarisation
122
how to mast cells contribute to bronchial hyper responsiveness?
by infiltrating the bronchial smooth muscle layer
123
what triggers release of histamine (and other inflammatory mediators) granules from mast cells ?
multivalent antigen cross-links bound IgE antibody- causes release of granule contents
124
name 1 biological effect of carboxypeptidases, try-taste or chymase
remodel connective tissue matrix
125
name 3 biological effects of histamine and heparin
increase vascular permeability
cause smooth muscle contraction
anticoagulation
toxic to parasites
126
name 1 biological effect of IL-4, IL-13 and IL-33 (cytokines)
stimulate and amplify Th2 cell response
127
name 1 biological effect of IL-3, IL-5 and GM-CSF (cytokines)
promote eosinophil production and activation
128
name 3 biological effects of TNF- alpha (cytokines)
promotes inflammation
stimulates cytokine production by many cell types
activates endothelium
129
name 1 biological effect of CCL3 (chemokine)
attracts monocytes, macrophages and neutrophils
130
name 5 biological effects of lipid mediators (prostaglandins (D2, E2) and leukotrienes (C4, D4, E4))
smooth muscle contraction
chemotaxis of eosinophils, basophils and Th2 cells
increase vascular permeability
stimulate mucous secretion
bronchoconstriction
131
name 3 biological effects of platelet activating factor (lipid mediator)
attracts leukocytes
amplifies production of lipid mediators
activates neutrophils, eosinophils and platelets
132
which characteristics are associated with neutrophil-prominent disease?
more severe
increase air remodelling
late onset
steroid resistance
133
why is asthma difficult to diagnose?
it is diagnosed via symptoms but as it is reversible a patient may feel unwell and then in a few hours feel absolutely fine again
134
how many times a week to use a SABA is too much?
asthma is uncontrolled if using it mote than twice a week
135
inhaler steroid counselling (2)
- ensure patient knows to take it even when they are feeling good- this is working
- rinse mouth/ brush teeth after using to reduce chance of getting oral thrush
136
why are Qvar and clenil not equal in dosing?
because of the difference in particle size, clenil is much bigger (10-15 microns) while Qvar is smaller (5 microns) - this is better for lung penetration
think how many letters in the word, smaller word, smaller particle etc
137
why are steroid inhalers prescribed by brand?
different names of the same drug are not equal in dosing ie Qvar vs clenil- difference in particle size
138
which kind of device is preferred for acute asthma ?
pMDI and spacer with titrated doses
139
if patient has poorly controlled asthma - what do we do? (2)
try LABA first- if no benefit then stop
then try leukotriene
140
step one of asthma plan
everyday asthma
preventer dose and counselling
reliever dose and counselling
141
step two of asthma plan
when I feel worse
what symptoms to look for
waking at night
needing reliever more than3x per week
peak flow drops
- increase preventer dose
142
step three of asthma plan
asthma attack
- Reliever isn’t helping or need it more than every 4 hours
- Difficulty walking/ talking
- Wheezing, tight chest
- Blue inhaler
*30-60 seconds between puffs- because, aerosol needs time – if don’t leave enough time -affects particle size and then lung penetration
- Can use up to 10 puffs
Then should call 999
If managed to deal with the attack in house
* See GP today
143
what is MART ?
maintenance and reliever therapy- a combined inhaler
144
caution with MART?
patient may take a high steroid dose
this should only be used a few times before seeking help
145
steroids in pregnancy?
Perfectly safe
Explain to concerned patients that the amount of steroid passed to baby if tiny IF ANY- explain that If lucky 50% of dose will go into lungs
The rest will stay in mouth or go to stomach
Some absorbed in mouth, lungs, stomach- after this- distributed to liver where it is metabolised, then systemic circulation, then can get to baby via trans-placental distribution- ie VERY small dose can actually get to the baby
If asthma is not well controlled during pregnancy- this poses a larger risk to baby via poor oxygen supply
146
asthma in labour?
have salbutamol near by (reliever)
make sure healthcare team are aware
