Lecture 22 - Infections in Asthma and COPD Flashcards Preview

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Flashcards in Lecture 22 - Infections in Asthma and COPD Deck (37):

All viruses exists as a _______


Genome + protein coat


Many have a host-derived..

lipid envelopes


What are the general features of virus replication

Viruses may be adsorbed to host cell

virus binds to surface receptor
Virus enters cell and is uncoated (genome is exposed)

Viral proteins translated and cleaved

Viral genome is replicated

New virus particles assembled

New virus particles released


neurominidase is a viral enzyme required for .....

the virus to leave the host cell - targwtted by tamifllu


What are the diverse viruses that infect the respiratory tract?



Why is there no broadly useful vaccines or antiviral available for resp infection

The diverse ypes of viruses have different ways of infection and many strains (which vary year to year)

also doesn't deal with the host reposen


At least some viral pathology is due to host response, how?

neutrophils release proteases and ROS
cytotoxic T cells lyse infected host cells


How do respiratory viruses cause harm

Airway macrophages ingest viruses. Many viruses abortively, replicate in macrophages
This causes:
- release of pro-inflammatory cytokines
- infection curtailed, but some local tissue damage

Influenza and some others are cytolitic - spread new cells and hosts

Non-lytic viruses induce cellular and cytokine resp.

Mucus + dead cells + inflammatory cells clog airways

Damaged airway epithelium becomes MORE PERMEABLE

BACTERIAL secondary infection is common


RSV is very common amongst...



Asthma has many....

Triggers (allergy, stress, cold, infection)



Treatments (but no cure)


over _ million Australians have asthma

2 million

1/8 children

1/10 adults


What does atopy mean?

allergy to innocuous substances


What are commonsals?

microbe that is normally present and causes no harm


What is more complicated usually URTI or LRTI?

Lower resp. tract infection


Eosinophilia is a key feature of ...

allergic asthma


What is the appropriate Th1 immune response to aeroallergens in the normal airway?

The activated Th1 lymphocyte produces cytokines (IFN, TNF-a) which stimulate macrophages


In asthma what is the Th2 immune deviation?

ACtivation of Eosinophils, Mast cells (histamine), Plasma cells (IgE) cause inflammation and mucous accumulation which clogs the airway - can also remodel and make smooth muscle thicker


TLR is a type of...

pattern (PAMP) recognition - first responders


TLR ligands may be:


Responsible for activation of phagocytes, release of inflammatory mediators


What is the hygiene hypothesis? (HH)

a lack of early childhood exposure to infectious agents increases susceptibility to allergic diseases, as the immune system does not properly develop

Risk of autoimmune disease is also increased


HH was identified via...

studies showing that eczema and hay fever were less common in larger families and with more older siblings


What is the proposed mechanism of HH?

Th2 immune responses predominate in babies, which promotes antibody production

Cytokine response to early infections leads to overall Th1 response:
- efficient pathogen clearance
- more mast cells, eosinophils, IgE

The infants immune system needs stimuli to develop regulatory T cells which mediate tolerance and dampen immune response


More recent work of HH reveals that...

Benefit of early infection depends on the type and timing of infection

more antibiotics now given in early life which affects colonisation of bowel by good bacteria


What are some points of evidence for the HH?

Allergic and autoimmune disorders less common in developing countries

migration from developing to developed world leads to greater incidence of these conditions

Early life exposure of mice to infections - a reduced incidence of autoimmune disease


What are some points of evidence against the HH?

microbial diversity may be more important than the numbfer of infections

Asthm rates are declining in some developed nations while food allergy continues to rise

many other factors linked to an increase in asthma and allergy:

delayed intro of solids
air polution
household damp and airbourne moulds
family history


Most asthmatics are atpoic, but only some atopic children...

progress to asthma


Long term birth cohort studies show 3 things which add together to form the greatest risk of persistent asthma, what are they?

LRTI + aeroallergen sensitization + family history of asthma


Why does respiratory infections link to an altered tolerance?

Viral infection alters normal maturation and turnover of dendritic cells

Early respiratory infection may be a sign of predisposition to asthma, and not a cause


Th2 cytokines stimulate...

IgE production


more severe LRTIs (e.g RSV) more strongly linked to athsma than ..

uncomplicated URTIs


Some risk factors of asthma overlap with the HH - what are they?

Inactivity / too much time indoors
- too little Vit D (impaired immunity)
- Obesity

c-section delivery - slight increase in asthma (don't get early colonization by mother's flora)

Ciggy smoke exposure irritates airways


What are the public health messages for HH and asthma?

Dirt is good, to some extent...

not all micro-organisms are harmful, but need to avoid serious infections (vaccination decreases occurence of infections that can kill or have permanart consequences - whooping cough, measles are BAD)


What are the treatments for asthma exacerbations?

initial treatment - inhaled B2-agonists and steroids

moderate cases: antibiotics, nebulized b2-agonists, oral steroids

severe cases: i.v bronchodilators

most severe: ICU - intubation


80% of asthma exacerbations are caused by ...

viruses - especially Rhinovirus


What is the trigger for interferon (IFN) produciton?

dsRNA - we don't make it, must be from virus


true or False

IFN is part of the innate immune response



Why do asthmatics get worse and longer colds?

Both +/- asthma had similar basal ICAM-1 levels

but, asthmatic cells have higher Rhinovirus replicaiton and delayed lysis - due to impaired apoptosis

asthmatic cells produced less IFN-beta

Adding IFN-beta to infected asthmatic cells induced apoptosis and reduced viral replication