Week #8 Flashcards

Question 1

Q

List some ways in which Mast cells can be activated internal and external

Answer

A

External

allergen (IgE)
stings
mechanical stimulation
uv light/heat
osmotic stimuli hypertonic saline
vancomycin

Internal

activated complement
neuropeptides

Question 2

Q

How does exercise induce a change in osmolarity and what is the effect on Mast cells?

Answer

A

in exercise minute ventilation rises and this causes loss of fluid in the airway and then consequently the osmolarity of the airway fluid rises and that change triggers Mast cell degranulation

Question 3

Q

Atopic individuals are those which?

Answer

A

Have produced allergen specific IgE that has now bind to Mast cells and has sensitised them

Question 4

Q

What is the intracellular signalling that occurs upon cross linking of the FcεR1 receptors upon IgE binding to allergen

Answer

A

Adjacent IgE molecules bind allergen (external)
Adjacent ΙgΕ receptor FcεR1 (α, β & 2γ) cluster
β & γ chains phosphorylated (internal)
Recruitment and activation of cellular tyrosine kinase Syk
Phospholipase C phosphorylation and activation and activation of the MAPK pathway
Phospholipase C goes onto cause degranulation through protein kinase C activity and Ca²⁺ release as well as activations of arachadonic acid metabolites and cytokine gene transcription
MAPK pathway also results in cytokine gene transcription and the activation of the arachadonic acid pathway

Question 5

Q

In a Mast cell response what is released at each time point:

Immediate?

Rapid (10-30 minutes)?

Late?

Answer

A

Immediate

release of preformed mediators, Histamine, Heparin, Tryptase, TNF-alpha

Rapid

Arachodonic acid activation
- Cys-LTs
- PGD₂

Slow

IL-4
IL-5
GM-CSF

Question 6

Q

Mast cells release IL-4, IL-5 and GM-CS, what is their role?

Answer

A

IL-4 reinforces the Th2 phenotype and results in more IgE production
IL-5 recruits eosinophils
GM-CSF promotes the survival of eosinophils and activates macrophages

Question 7

Q

What are some of the actions of histamine and where is it acting? i.e. H1 or H2

Answer

A

Pain & itch (sensory nerve activation) (H1 receptors)
Bronchospasm (H1 receptors)
Mucus secretion (H1 receptors)
Vasodilatation - hypotension (H1 receptors)
Increased vascular “leak” - hypovolemia (H1 receptors)
CNS - increased wakefullness (H1 receptors)
Positive inotropic and chronotropic (H2 receptors expressed in heart)
Gastric acid secretion (H2 receptors)

Question 8

Q

Product of AA metabolism: Cyteinyl leukotrienes

How is LTC₄synthesised?

What is the action (local and systemic) of LTC₄and metabolites (LTD₄ and LTE₄)?

Answer

A

Glutathione-S-transferase is responsible for the synthesis of LTC₄ from LTA₄
LTC₄ and metabolites (LTD₄and LTE₄) act on CysLT1 receptor
- Thought to have a mainly pathophysiological role and so are a good drug target
- Local action can include airway smooth muscle contraction causing bronchoconstriction and can also cause increased mucous secretion and oedema
- Systemic action-together with histamine can cause massive vasodilatory response contributing to anaphylaxis
- also cause leak from vessels which together with histamine can cause hypovolemia

Question 9

Q

The Arachodonic acid pathway is split into two parts, what are they?

Answer

A

The prostoglandin half and the leukotriene half

Question 10

Q

What are some of the drug targets in the Arachodonic acid pathway

Answer

A

Note that aspirin has no real effect in asthma indicating that PGD₂ has a limited role to play even thoug it is a bronchoconstrictor

Question 11

Q

Role of cytokine release by Mast cells upon activation in alergy.

What are the cytokines released and what is the role of each?

Answer

A

IL-4 (Th2 IgE), IL-5(eosinophil recruitment), TNF and GM-CSF(eosinophil survival and macrophage activation)
produced in response to activation of transcription factors-so it is a slow onset

Question 12

Q

What are some inhibitors of mast cell activation

endogenous and exogenous

Answer

A

endogenous=PGE₂, adrenaline and cortisol
Exogenous (pharmacological)
- Disodium cromoglycate/Nedocromil sodium
- Omalizumab

Question 13

Q

Omalizumab

Answer

A

A humanised murine monoclonal antibody
Administered subcutaneously
Omalizumab directed against the alpha subunit binding region of the IgE
The IgE can no longer bind the high affinity receptor on the Mast cell
Must be administerred sub-cutaneously and is very expensive

Question 14

Q

Disodium cromoglycate/Nedocromil sodium

Answer

A

very well tolerated
modest anti-inflammatory action only
not effective in all patients
reduction in Mast cell activation but mechanims not entirely clear
- cause annexin-1 release which can resolve inflammation as it
  - annexin-1 is one of the medaitors of the glucocorticoid ant-inflammatory activity
    *

Question 15

Q

H1 receptor antagonists

Answer

A

urticaria
atopic dermatitis (adjunct to steroids)
hayfever (allergic rhinitis)
anaphylaxis & angioedema (adjunct to adrenaline)
bites & stings
motion sickness (muscarinic antagonist activity)

Note that H1 receptor antagonists are not useful in colds or asthma

Question 16

Q

Are H1 receptor antagonists good for treating colds and asthma?

Question 17

Q

What are the three generations of antihistamines (i.e. H1 receptor antagonists)

Answer

A

Sedative- chlorpheniramine, promethazine
- Sedation may be neutral/beneficial in treatment of allergic condition, but sufficient to interfere with lifestyle.
Non-sedative (poor entry into CNS)-terfenadine, astemizole
- Lack anti-muscarinic activity and GIT effects but can cause rare, sudden ventricular arrhythmia (withdrawn)
Newer non-sedative agents-cetirizine, loratidine
- Reduced risk of unwanted cardiac effects

Question 18

Q

What are the two phases of Type I Hypersensitivity?

Answer

A

Sensitization
Response (effector phase)
- local or systemic (rare)
  - Local=rhinitis, bronchoconstriction, conjunctivitis
  - Systemic=anaphylaxis
- Responses have an immediate and a delayed phase

Question 19

Q

DC cannot actually make IL-4, so how are Th2 cells induced?

Answer

A

DC make IL-33 instead which then acts on nearby basophils which then make IL-4 which then acts on the T cells to induce the Th2 phenotype and they go on to make more IL-4 themselves
New Nature paper says now that perhaps basophils express MHC-II and can stimulate CD4 T cells directly

Question 20

Q

Wheal and Flare (type I hypersensitivity)

Answer

A

immediate (minutes)
due to preformed mediators from mast cells
redness-vasodilation
soft swelling-leakage of plasma from venules
dependent on IgE

Question 21

Q

Late response (hypersensitivity type I)

Answer

A

Late (hours-days)
due to induced mediators from mast cells (leukotrienes, cytokines etc)
hard swelling-accumulation of leukocytes
neutrophils, Th2 cells and eosinophils

Question 22

Q

Allergic reaction can occur in the skin, GI tract or airways or blood vessels

what occurs in each?

Question 23

Q

Eosinophils involved in late phase response (cellular response)

how do they cause damage?

how are they activated and recruited?

and what happens to them when they are activated?

Answer

A

produce toxic granule-derived basic proteins and free radicals
- responsible for tissue damage/remodeling
produce chemical mediators
- Epithelial cell activation, inflammatory cell recruitment and activation

Special Chemokine produced by epithelial cells is called eotaxins and is responsible for eosinophil recruitment

Decreased threshold of activation and degranulation
(increased senstivity)

after activation get ↑ number of FcERI on surface and IgE binding
- decrease the threshold for activation

Question 24

Q

How do corticosteroids work against allergies?

Answer

A

inhibit the transcription of many pro-inflammatory genes (cytokines etc) and cause broad immunosupression
so can be harmful in that we get a non-sepcific dampening of the immune response which could lead to susceptibility to infection
another side effect is bone deminerilization
because of both of these reasons prolonged use is not recommended

Question 25

Q

Immunotherapies/Desensitization

Answer

A

Attempt to induce tolerance
T cell tolerance
- may induce anergy
- switch the Th response-perhaps to Th1
- induce apoptosis
- or perhaps throught the induction of a Treg response

Question 26

Q

Type IV hypersensitivity

Answer

A

A Th1 response but can involve CD8 T cells in some cases
Can be elicited by
- microbial infection
- intradermal injection of protein antigens
- contact with chemicals etc absorbed through skin
There is a sensitization phase where Th1 cells are induced and travel back to site of exposure
But there is no immediate response (no wheal and flare)
- that is becasue the response is all cellular

Question 27

Q

What is the mechanism of conntact hypersensitivity?

(Delayed Hypersensitivity type IV)

pentadecacatechol as example

Answer

A

thought that because pentadecacatechol is so small it must haptenise by binding to some other intracellular protein and then that is expressed on MHC-II molecules
licensing of DC occurs and activation of Th1 cells
this is sensitization
and then on secondary exposure we get a response that is seen as the delayed type hypersensitivity IV
- Th1 and IFNy production

Question 28

Q

Mycobacterium Tuberculosis is a Type IV hypersensitivity?

Answer

A

yes
infects the macrophages
M.tuberculosis multiply in macrophage and then CD4 T cells and CD8 T cells will arrive to try to clear infection and then basically it just goes in circles
so the immune system just walls the infeciton off and these are called granulomas
The good news is that the DTH response restricts the growth of the microbe, so that 90% of those infected are not infectious and never know they are infected
The bad news is that in a small number of individuals, the DTH response interrupts respiratory function

Question 29

Q

Celiac Disease

Role of DQ2, tTg2 and gliadins

Answer

A

type IV but need repeated exposure (so kind of like contact hypersensitivity as opposed to the TB hypersensitivity)
DTH response that targets components of gliadin protein and then this leads to damage of the small intestine-hyperplasia of villin etc results in low metabolism in the gut
90% of patients are HLA DQ2 positive
also the presence of autoantibodies to gliadins and Tissue transglutaminase are an indicator

Role of DQ2, tTg2 and gliadins

HLA-DQ2 prefers amino acid side chains with negative charges
because the pocket is positively charged
gliadins-rich in glutamine=positive charge
but then tTg2 changes then glutamine to glutamate so that it can can bind DQ2 very easily (deamidation)

Question 30

Q

Diagram of Celiac disease pathophysioogy

Question 31

Q

Post puberty are men or women more likely to get asthma?

Question 32

Q

Asthma inflammation

Diagram of cells and mediators

Question 33

Q

What are the classes of drugs used to treat airway obstruction? Provide an example of each

Answer

A

Relievers-relieve ASM shortening,
controllers-control ASM shortening,
Preventors-prevent ASM shortening, prevent bronchiol wall oedema and prevent mucus hypersecretion

Question 34

Q

What happens if you get a person to do shallow breathing for an hour? i.e. what happens to their airways?

what happens in expiration

Answer

A

The ASM will actually be more likely to contract due to less filling of the alveoli with air and thus less resistanc to ASM contraction
can convert someone to an asthmatic airway phenotype
In expiration load decreases and there will be an increase in airway resistance and an increased liklihood of airway collapse

Question 35

Q

What is the airway smooth muscle contractile mechanism in response to calcium?

Answer

A

Increase in intracellular calcium
Acivation of calmodulin and this activates myosin light chain kinase
Myosin light chain is phosphorylated and then causes the actomyosin filament to acquire ATPase activity
The ATPase activity allows for energy for the cross bridges to cycle
cross bridges between actin and myosin break and reform sliding past each other resulting in overall cell shortening

Question 36

Q

The contractile mechanism

How does the intracellular Ca²⁺ levels rise?

How does the intracellular Ca²⁺ levels fall?

Answer

A

Increase

Phospholipase C acivation which leads to inositol trisphosphate activation which causes Ca²⁺ release from intracellular stores

Decrease

plasma Ca²⁺ATPase - extrusion across plasma membrane sarcoplasmic reticulum Ca²⁺ATPase (SERCA)
- increase uptake of calcium into internal SR stores

Question 37

Q

Cysteil Leukotrienes are __?__ times as potent as histmaine in terms of bronchoconstriction?

Answer

A

300

and provide a much more protracted response-i.e. effect remain for longe

Question 38

Q

Endogenous mediators that relax airways and endogenous mediators that contract airways?

Question 39

Q

What is the role rho kinase and protein kinase C?

What is the role of protein kinase A?

Answer

A

inhibits myosin light chain phosphatase
activate myosin light chain phosphatase

Question 40

Q

What is a definition of airway hyperesponsiveness?

Answer

A

Airways respond to early and by too much to histmaine leukotrienes etc

Question 41

Q

Short acting Beta-2 Adrenoceptor agonists?

Adverse effects?

Answer

A

Short-acting - salbutamol, terbutaline (SABA)
mainstay of acute bronchodilator therapy
Key features- short acting agents: rapid (2 - 5 min) onset β₂ selective (very important)

Adverse effects

tachycardia, tremor, hypokalemia
Other features- variable degrees of efficacy
Tolerance (measurable - may be important)
increasing evidence showing that suggests increased use may cause increased morbidity in certain individulas

2

Question 42

Q

How does the Beta-2 Adrenoceptor relax airway smooth muscle?

and what is the action of protein kinase A (3 main actions)

Answer

A

Receptor has Gs protein coupling which activates adenylate cyclase which generates cAMP
cAMP activates protein kinase A
protein kinase A indirectyl increases activity of SERCA and inhibit the IP₃R calcium receptor
Protein Kinase A also acts to phosphorylate the myosin light chain kinase to deactivatge it and can also phosphrylate and activate the myosin light chain phosphatase

Question 43

Q

Long acting Beta Agaonists (LABA)

Why is it administerred concomitantly with an inhaled GCS

Answer

A

Salmeterol - slow onset, 12 hrs duration (twice daily)
Formoterol - rapid onset, 12 hrs duration (twice daily)
Indacaterol - rapid onset, 24 hrs duration (once-daily)

reduce number of exacerbations - anti-inﬂammatory?

beneﬁt of chronic bronchodilatation

Side effects

tolerance develops to bronchoprotective effects
same with the SABAs in that with extensive usage may result in increased asthma morbidity
indicated for prophylaxis only
monotherapy associated with increased morbidity/mortality

Because the rationale is that asthma is bad enough to justify a LABA it should also be combined with inhaled GCS in single actuator

Question 44

Q

Muscurinic receptor antagonists

How do they stop ASM contraction

and name two examples and there time of action

Answer

A

parasympathetic cholinergic nerves into the airway that terminate adjacent to smooth muscle
upon irritation of the airways etc the nerves are activated and acetylcholine released from the nerves act on M3 receptors on the smooth muscle and cause contraction
Ipratropium bromide-short acting
Tiotropium bromide-long acting (LAMA)

Question 45

Q

The lung works to maintain a:

PaO₂=?

PaCo₂=?

pH=?

Answer

A

PaO₂ refers to partial O₂ pressure in the arteries

100mmHg

40mmHg

7.4

Question 46

Q

Capital A=

lowercase a=

I=

V=

Answer

A

Alveolus

artery

reffering to inspired air

veins

Question 47

Q

Image of pulmonary diffusion across the alveolar capillary membrane

What are someof the properties of the membrane

Answer

A

The membrane is epithelium of the alveolus and a monolayer of endothelium of the blood vessel and is designed for diffusion due to:

Thin = 0.5 micron
Large surface area = 50 - 100 m
Alveolar volume = 3 - 6 L
Capillary volume = 80 ml
(greater if ↑ cardiac output)

Question 48

Q

The two kinds of work associated with inspiration are?

Answer

A

Insipration is an active process as the friction must be overcome-resistive work of breathing
and work of overcoming the elasticity of the lungs is the elastic work of the lungs

Question 49

Q

3 main functions of the Respiratory system are?

Answer

A

Oxygenate pulmonary arterial blood
Remove carbon dioxide from blood
Maintain acid-base balance
(because CO₂ is an acid)

Question 50

Q

What are the muscles involved in inspiration and what is their innervation

At rest what is the WOB of these muscles?

Answer

A

The diaphragm is the main muscle and it is innervated by the phrenic nerve
The external ICM which are innervated by the intercostal nerves
3% of total oxygen usage

Question 51

Q

If there is an obstruction of airflow the resistive work of breathing will be much higher and expiration will also become active

What are some consequences of this obstruction?

Answer

A

Recruitment of accessory muscles (scalene and sternomastoid muscles)
Increased oxygen consumption by respiratory muscles
Risk of respiratory muscle fatigue, if the airway obstruction is severe
respiratory muscle fatigue can lead to ventilatory failure which is said to occur when PaCO₂is greater than 50mmHg

Question 52

Q

What are the pressure changes during expiration and inspiration that occur in the alveolar space and the pleural cavity?

Question 53

Q

Normal FEV1/FVC is?

and what happens to the FEV1 and FVC during obstructive pulmonary disease?

Answer

A

Normally is around 80% in young healthy individual
should always be above 70% even in the more elderly
In OPD the FEV1/FVC can be very low=39%

Question 54

Q

Normal flow loops and abnormal flow loops due to Obstruction

Answer

A

flow loops are flow vs volume graphs
usually triangular in expiration and rounded in inspiration
If obstructed the expiration may be flattened

Question 55

Q

In general the breathing pattern of someone with airflow obstruction will be?

Answer

A

deep, slow breaths

Question 56

Q

Gas Trapping?

Answer

A

In some cases of severe airflow obstruction affecting the lower airways, air can be trapped beyond obstructed airways
- ie it can be inspired but not exhaled.
This causes high TLC, RV and RV/TLC
(measured by body plethysmography, not by spirometry)

Question 57

Q

What arre the effects of airway obstruction?

i.e. physiological effects

Answer

A

Increased sensation of breathing
Increased respiratory muscle effort
Active exhalation
Prolonged inspiration and expiration
Altered pattern of breathing
Reduced maximum ventilation
(Gas trapping in some cases)

Question 58

Q

Ventialtion perfusion ration (V/Q)

What is normal?

what is abnormal and what is the consequence of a low V/Q?

What is the bodies response to low V/Q?

Answer

A

Gas exchange efficiency depends on equal perfusion and ventilation of a single alveolar-capillary unit so we want equal numbers of O₂ moleucles arriving with heamoglobin numbers
consequence of uneven ventilation means that in some A/C units there will be less ventilation and therefore blood will not be fully oxygenated as it leaves a low V/Q unit
Shunt is an extreme form of low V/Q where V/Q=0
compensatory mechanism where lung redirects blood flow from airways not being well ventilated is achieved through arterioles constriction
However this compensation is not fully complete and this can have downstream effects such as raising pulmonary artery pressures
*

Question 59

Q

High V/Q?

Answer

A

High V/Q units result in wasted ventilation because there is more ventilation of units than is required to oxygenate any blood passing through these units
- → ↑ physiological dead-space (with little effect on PaO₂)

Question 60

Q

The A-a gradient for oxygen

Answer

A

We can measure the P_aO₂ but we must estimate the P_AO₂
Use the ideal gas equation
P_AO₂ = P_iO₂ – P_aCO₂ / RQ
use 0.8 for RQ and 150mmHg for P_iO₂ as sea level
A (A-a) gradient equals the P_AO₂-P_aO₂
normal is <15 to 30
if higher than 30 than there is a gas exhange abnormality
- i.e. overall gas exchange is lower than would be expected with that level of O2 in the alveoli

Question 61

Q

Eclipse phase of viral replication is?

Answer

A

eclipse period-all the virus components are being made and then they are assembled within the cells and then they are released.
For every single cell that has been infected by one virus we have 10^8 viral particles coming out

Question 62

Q

Viral replication cycle diagram

Question 63

Q

What are the receptors for HIV virus on host cells?

and what is the ligand that HIV virus uses?

and what is thr process of binding?

Answer

A

CD4 is one of the receptors
CCR5 is the the co-receptor
sometimes the virus can change to CXCR4 and swap the mode of infection into cells.
glycoprotein 41 and glycoprotein 120

Binding of gp120 to CD4 triggers conformational change of the glycoprotein
this conformation change allows for the hydrophobic gp41 to move outsdide of the gp120 and then this allows for binding to the CCR5

Question 64

Q

What are the two methods of viral penetration into the host cell?

And what does HIV do?

Answer

A

Fuse with membranes if they have envelopes
either virus type (enveloped or not enveloped) can also enter through endocytosis which invoves invaginations of the cell membrane to form vesicles in the cell cytoplasm
uncoating then occurs
HIV binds to the cytoplasm and releases contents

Answer 57

A

Nucelus
Cytoplasm
HIV is a RNA virus but must replicate in the Nucleus as it has to integrate into the host genome.
Poxvirus is a DNA virus but is so big it doesnt have to fuse with host genome and just uses all its own DNA

Answer 58

A

means that the RNA is the same as the mRNA
so protein components can be synthesised
But need a RNA dependent RNA polymerase to replicate more genome-no such polymerase exists in our cells
Polio virus can undergo translation of the +ve sense RNA which will then fold in certain way such that active sites are constructed
then the proteins are autocleaved into the various compenents and one of the compenents is a RNA dependent RNA polymerase
*

Answer 59

A

do not
poxvirus
- carries entire genome and replicates in cytoplasm
  *

Answer 60

A

do
don’t
retroviruses

Answer 61

A

envelopes
non enveloped or enveloped

Answer 62

A

Patches of viral envelope glycoproteins accumulate in the host cell plasma membrane.
Capsid proteins and nucleic acid condense directly adjacent to the cell membrane.
The membrane surrounding the nucleocapsid then bulges out and becomes “nipped off” to form the new enveloped virion.

Answer 63

A

Some enveloped viruses utilize the cellular secretory
pathway to exit the cell. Virus particles enclosed within Golgi derived vesicles are released to the outside of the cell when the transport vesicle fuses with the cell membrane.

Answer 64

A

Genetic mutation, especially is RNA viruses with low fidelity polymerases
Recombination
- swapping parts of the viral genome due homologous recombination-so can only be achieved between related viruses
Reassortment
- when two different viruses infect the same host and if the viruses have segmented genomes then there can be swapping of sections of genes.

Answer 65

A

used to treat herpesvirus infections
when DNA is being synthesised new bases are incorparated into the growing chain as nucleoside trisphophate
Acyclovir is a gaunosine analogue
- but it is not cyclic so does not have the 3’ OH group require for continuation of the chain
- But it does that the 4’ OH group to allow incorparation of the acyclovir into the DNA chain
Acyclovir does not kill or cells becasue we do not have the enzyme required to add the first phsophate group onto the molecule so it cannot be incorparated into our DNA as it is not tri-phosphorylated
- Herpesviridae has Herpesviridae thymidine kinase enzyme that is able to add this first phosphate group
  *

Answer 66

A

Mucus which traps any viral particels
cilia which can beat up th mucus and can then be coughed up
alveoli macrophages
temperature gradient
- i.e. lowe temperature in the upper airways
IgA in the respiratory tract

Answer 67

A

rhinovirus infects the upper respiratory tract but remain localised to the upper airways as it grows better in the cooler airways of the throat and nose

Answer 68

A

rhinovirus, coronavirus, adenovirus
adenovirus
influenza virus, RSV
parainfluenza
RSV, parainfluenza 3
RSV, parainfluenza 3, influenza virus, adenovirus

Answer 69

A

Measles
Virus starts replicating in the URT, and then drains to lymph node and infects macrophages, lymphocytes and dendritic cells.
Then the measles virus goes all around the body and infects all areas.
It can also return to epithelial cells in lung and mouth.
The infection is highly contagious and can result in transient immunosupression due to the infection of the immune cells

Answer 70

A

sequestration in intestinal contents (constant movement of contents and allows contact with specific receptors)
mucus
stomach acidity
intestinal alkalinity
proteolytic enzymes secreted by the pancreas
lipolytic activity of bile
IgA
scavenging macrophages

Answer 71

A

non enveloped

Answer 72

A

M cells ingest and deliver antigens to underlying lymphoid tissue by transcytosis
Some enteric viruses use this pathway to gain entry to deeper tissues, others infect and destroy M cells

Answer 73

A

Rotavirus is spread via feacal oral route and must be very hardy to survive passage through the gut and in the environment
has a triple caspid
- core capsid, inner capsid and outer capsid
infects and destroys intestinal epithelial cells and M cells and causes diarrhea
- through the decreased absorption of the enterocytes
NSP4 protein secreted by the virus also increases the fluid secretion of the remaining intestinal cells, which intensifies the diarrhea

Answer 74

A

Part of the Picornavirus family
Virus enters via aerosol or ingestion and then replicates in the oropharynx and then can get into blood-vireamia
will also repilcate in respiratory tact and whilst in the intentine will be shed in feaces
vireamia can result in different systemic infections
- menigitis-many enterovirus infections
- CNS infection (polio)
- Skin-Group A Coxsackie virus-oral ulcers and hand foot and mouth disease
- Muscle-Group B Coxsackie virus-myocarditis

Answer 75

A

lymph node

Answer 76

A

the plasma
or cell associated

Answer 77

A

So infection may begin in peripheral epithelial tissue and then migrate to blood through lymph node-primary viraemia
the virus may then migrate to liver or spleen where it will replicate up to large numbers and then migrate back into the blood-secondary viraemia

Answer 78

A

must be able to cross the placenta
Can cause death and abortion by cytocidal viruses (eg.smallpox)
Can cause developmental abnormalities by non-cytocidal viruses (eg. rubella, CMV)

Answer 79

A

death and abortion by cytocidal viruses (eg. smallpox)
developmental abnormalities by non-cytocidal
viruses (eg. rubella, CMV)
- babies often have mental defficiencies and heart defects etc

Answer 80

A

URT with the cooler temperatures
In the intestinal tract
in lymphoid cells
In large airways
- need tryptase clara enzyme sectreted by the cells

Answer 81

A

Antibody
- antibody-dependent enhancement of infection by FcR-mediated uptake of virus-Ab complexes into cells eg. Dengue hemorrhagic fever/shock syndrome
- antigen-antibody complexes deposited in the
  kidney can cause glomerulonephritis and in the blood vessel, vasculitis eg. Hep B in chronic carriers
CD4 T cells
- responsible for some viral rashes eg. measles
- induce cytokines that recruit eosinophils responsible for bronchiolitis in infants with respiratory syncytial virus (RSV) infection
CD8 T cells
- contributes to liver damage in Hep B virus infection
  - lysis of hepatocytes, recruitment of monocytes
    and neutrophils
  - yellow skin and eyes are a sign of liver damage
  - old RBCs are destroyed by
    macrophages in spleen
  - heme from the hemoglobin is
    converted to bilirubin (yellow)

Answer 82

A

eg. HIV: replicates in CD4 T cells and kills
them and in monocytes and inhibits their
function
eg. measles: temporary immunosuppression from nonproductive replication in T cells and macrophages; suppression of proliferation of non-infected T cells by infected DC displaying measles surface glycoproteins; suppression of IL-12 production
- leads to susceptibility to secondary
  infections

Answer 83

A

molecular mimicry: Guillain-Barre syndrome which is a result of influenza proteins mimicing myelin-can result in demyelination of nerves
Polyclonal B cell activation: by EBV

Answer 84

A

Change in the antigenic structure of the virus
Due to selection of variant viruses with amino acid substitutions in the viral glycoproteins that allow the virus to escape neutralization by pre-existing
antibody.
Variant viruses arise spontaneously through errors in RNA replication giving rise to point mutations in the genes.
In influenza, antigenic drift occurs on a population scale with different mutations accumulating as the virus moves from person to person. In HIV infection a diversity of strains may develop within a single patient

Answer 85

A

antigenic variation will lead to the CTL not recognising the virally infected cell
HIV nef induces endocytosis of the Class I MHC
HSV protein binds to the cytosolic sode of TAP transporter and prevents peptide translocation to ER
- CMV can do the same but on the luminal side
adenovirus binds to MHC peptide complex in ER and anchors it there so it cannot get to the surface
EBV in latently infected B cells inhibits the proteasome
HIV, RSV, and adenovirus can shut down class I gene expression

Answer 86

A

Herpesviridae
*

Answer 87

A

Human CMV encodes an MHC Class I-like molecule that is expressed on surface of infected cell and delivers a negative signal to NK cell but cannot itself
present peptides to CD8 T cells

Answer 88

A

Antiviral activity of interferons is mediated by the induction of particular cellular proteins or pathways in the IFN-treated cell

Answer 89

A

PKR phosphorylates itself in the presence of dsRNA
and then PKR phosphorylates eIF2alpha and that results in decreased translation of protein which inhibits viral replication

Answer 90

A

PKR needs long stretches of dsRNA to wrap around and become activated

EBV and adenoviruse make many small stretches of RNA-not long enough for PKR binding
Vaccinia and reovirus encodes molecules that bind the dsRNA instead and prevents PKR activation
Vaccinia uses a viral encoded homologue of eIF2alpha which competes for PKR which inhibits phosphorylation of eIF2alpha

Answer 91

A

Inherited defects eg. absence of Ig class
Polymorphisms in genes controlling immune responses eg. MHC genes
interferon-inducible genes (MxA and MxB)
- proteins that interfere with the influenZa life-cycle
receptor genes eg. CCR5
- In HIV infections a delta 32 mutation in CCR5 can prevent HIV infections

Answer 92

A

age - newborns and the aged are more susceptible to severe disease (immature and waning immune response) but young suffer less from immunopathology
malnutrition - decreases resistance
hormones, pregnancy - males and pregnant
women more susceptible
dual infections - may result in more severe
disease
- confusing Th1 and Th2 responses

Answer 93

A

Conducting part

nasopharynx, trachea, bronchi, bronchioles. Carry and condition air

Respiratory parts

only the alveoli

Answer 94

A

for phonation and conditioning of air
for smell
turbinates warm the air and and moistens the air, failure to do so would result in dehydration

Answer 95

A

epiglottis and larynx divert food and drink from airways
larynx (uppermost part of trachea) is organ of phonation (sound production)
Air forced over vocal cords leads to vibrations

Answer 96

A

line nasopharynx and airways but these are the conductiong vessels-counterintuitive-not areas of respiration
pseudostratified columnar epithelium with cilia (30%)
lots of goblet cells and deep glands (30%)
sensory cells to initiate coughing to expel irritants (3%)
Basal (stem) cells (30%) in base of epithelium renew the epithelium
Serous cells (3%)

Answer 97

A

Mucus layer, (with trapped particles) swept upwards by cilia to epiglottis
Ends up in the stomach for sterilisation
Smoking destroys cilia, so cough must shift mucus
upwards from the lungs

Answer 98

A

Beneath the larynx is the trachea
Comprised of a stiff wall of hyaline cartilage that is C shaped with trachealis muscle on the back
smooth muscle is also there which can contract when we try to cough something up

Answer 99

A

mucosa, submucosa and adventitia
Mucosa is comprised of the respiratory epithelium sitting on a lamina propria
Submucosa is comprised mainly of connective tissue with large mucus glands which produce the mucus of the respiratory tract
Adventitia contains cartilage and outer layer
of connective tissue

Answer 100

A

Initially like trachea, but thinner walls
Cartilage ring becomes cartilage plates in intrapulmonary bronchi
Smooth muscle at the boundary between the lamina propria and submucosa
Glands still present
Lymphoid nodules present

Answer 101

A

Bronchioles have no cartilage but there is still a respiratory epithelium with smooth muscle
Bronchioles steadily loose goblet cells and ciliated cells and we get more clara cells as the vessels keep branching-but still conduction vessels
goblet cells dissapear then ciliated cells-important that as this is the way that the cilia can sweep up all the mucous dripping down

Answer 102

A

Clara cell-columnar/cuboidal with short microvilli (projections that cannot move)
produce surfactant to destroy surface tension because the airways are moist-soap or detergent allows us to keep airways open
Clara cells may neutralise toxins and become more common with more branching of conducting pathways

Answer 103

A

Last part of the conducting system still have SM-single layer or two layers
no goblet cells
still cuboidal epithelium with some cilia but mainly clara cells with microvilli
Give rise to respiratory bronchioles

Answer 104

A

First respiratory structures, alveoli, appear intermittently
Alveoli are thin walled pouches
The epithelium of the respiratory bronchiole is cuboidal to squamous
- in an attempt to be thin
It gives rise to alveolar ducts, chains of
connected alveoli.

Answer 105

A

chaotic network of little cells
simple squamous epithelium
walls contain the respiratory capillaries
there are pores between alveoli which connect alveoli. Through the hole gas can permeate
Between alveoli are the intralveolar septum
Intralveolar septum contain elastin fibres which keep alveoli from collapsing
positive pressure that intermitently occurs keeps the alveoli open

Answer 106

A

Epithelial cells present in the alveoli are called pneumocytes
Type I pneumocytes are the flat squamous ones which are those which form the majority of the surface area of the alveoli (95%) and provide exchange surface
Have tight junctions to prevent extracellular fluid leakage and sit on basal lamina

Answer 107

A

Type II pneumocytes are more prevelant that type I but are only about 5% of the area-so tightly packaged in together
sit at angles between alveolus septa and they produce surfactant which again prevents collapse of the airways due to how the surfactant reduces surface tension

Answer 108

A

stem cells
as they can regenerate into either type I or type II pneumocytes.

Answer 109

A

Consists of surfactant, type I pneumocyte, basal lamina, connective tissue, basal lamina endothelial cell plasma

In thinnest barrier, two basal lamina can fuse and there is no connective tissue

so in thinnest part the endothelial cells and the type I pneumocytes can share a basal lamina

Answer 110

A

sometimes dust particles can make it into the alveoli
need macrophage to deal with the dust
Macrophages have techincally left body and enterred alveoli
When “full”, they migrate up to the airways until they are carried off by the ciliated cells
Some macrophages end up in interalveolar septum
loaded with particles