Lecture 22 - Infections in Asthma Flashcards
Describe the structure of viruses
Nucleocapsid:
• Genome (ss/ds RNA/DNA)
• Protein coat
+/- Envelope
Describe briefly viral life cycles
Viruses must use host machinery to replicate
Hence, viruses must infect host cells
Invasion:
1. Adsorbtion of virus to cell
• Non specific charge interactions
- Virus binds receptor on host cell
- Entry of virus into cell:
• RME
• Fusion of host and viral membrane - Uncoating of virus
- Replication:
• Translation of larger polyprotein, followed by cleavage
• Genome replication - Assembly of virions
- Release:
• Lysis of host cell
• Budding
Describe the structure of the influenza virion
Genome: 8 dsRNA segments Envelope HA, NA, & M1 embedded in membrane Other enzymes: • NS-1 etc.
Describe the structure of the RSV virion
(Respiratory syncytial virus)
Genome: (-) ssRNA \+ structural proteins: • L: large polymerase protein • N: nucleoprotein • P: phosphoprotein
Envelope \+ embedded proteins: • G: attachment protein • F: fusion protein • SH: small hydrophobic protein • M: matrix protein
List some viruses that infect the human respiratory tract
RSV
• Common cold
Influenza
Rhinoviruses
• Croup
Corona viruses
• SARS
What drives much of the pathology in viral respiratory infections?
Host response:
• Over-exuberant neutrophil responses: protease and ROS release
• CTL lysis of infected cells
Describe how respiratory viruses cause harm
Alveolar macrophage infection:
• Kills cells
• Cytokine release
Lytic viruses:
• Kills host cells
Non-lytic viruses:
• Induction of cellular immunity & cytokine response
Result:
• Mucous, dead cell debris, & inflammatory cell infiltrate in airways
• Damaged epithelium is more permeable → secondary bacterial infection
Describe the heterogeneity of asthma
Many genes involved
Many presentations
Onset can be in childhood or adulthood
• Many children outgrow asthma
• Some only develop it in response to triggers experienced later on in life (e.g. in the workplace)
Many triggers
• Stress, allergens, cold, exercise
What is the prevalence of asthma?
1 in 8 children
1 in 10 adults
Mortality decreased considerably since 90’s
Incidence is increasing
Define atopy
Tendency to form inflammatory and immune responses to innocuous substances
What are URTI and LRTIs?
URTI: upper respiratory tract infection
LRTI: low respiratory tract infection
Define eosinophilia
Preponderance of eosinophils in airway tissues and blood
This is a key feature of allergic asthma
Describe the normal response to aeroallergens in the airway
- Th1 preponderance (over Th2)
- Th1 cytokines (IFNgamma) stimulate low level macrophage response
- Th1 cytokines privilege low level IgG response
→ physiologic response • Don't have mucous hyper secretion • No epithelial thickening • No sub-epithelial fibrosis • No airway oedema • No bronchoconstriction / SM hyperplasia
Describe the allergic response to aeroallergens in the airway
- Th2 preponderance
- Th2 cytokines (IL-4, IL-5, IL-13):
• Recruit eosinophils and mast cells
• Stimulate B cells to IgE class switching - Eosinophils release:
• MBP (major basic protein)
• ECP (eosinophil cationic protein) - Mast cells release:
• Histamine
• Leukotrienes
• Prostaglandins
→ allergic response • Goblet cell hyperplasia • Airway oedema • Thickened airway epithelium • Subepithelial fibrosis • Bronchoconstriction / SM hyperplasia
How are microbes sensed in the early stages?
What does this result in?
PAMPs on microbes sensed by PRRs
e.g. TLR4 - LPS
TLR3 - dsRNA
Results in the release of pro-inflammatory cytokines, which initiate the response against the pathogen