D4 Lungs

Question 1

Describe Severe COVID

Answer 1

High levels of viral replication 
Cytokine storm: IFNy, IL-1B, IL-6, IL-12, IL-17, Il-18, TNFa
ARDS
High acute phase reactants
Cell free hemoglobin
Lymphopenia & eosinopenia 
Microinflammed endothelium & DIC  

severe disease, prolonged viral clearance, organ failure, DIC(disseminated intravascular coagulation)

Question 2

Describe low-dose Covid infection

Answer 2

Effector T & Bc immune response
Development of virus-specific neutralizing IgM, IgA, IgG

Rapid viral clearance & indolent disease

Question 3

what Th response is required for protection against COVID

Answer 3

Th1/Th17

- Dysregulation of the immune response can result in a cytokine storm

Question 4

Defence mechanisms in the lung (8)

Answer 4

Epithelial cell turnover
Epithelial tight junctions
Ciliated epithelium
Goblet cell mucus
Airway gyro-dynamic shape
Cough, sneeze reflexes
Lysozyme, lactoferrin, complement, defensins
Alveolar macrophages, mast cells & eosinophils

Question 5

Describe Type 1 pneumocyte Alveolar epithelial cells

Answer 5

Extremely thin (0.2 microns)
Squamous cell, often below limit of detection
Minimal covering for capillaries
Supported by reticular connective tissue and a basal lamina

Question 6

Describe Type 2 pneumocyte Alveolar epithelial cells

Answer 6

Cuboidal cells – interspersed among Type 1 cells,
located at the angular junctions of alveolar walls
Characterized by a reddish, foamy or vacuolated cytoplasm
Secretory in nature
- Makes SURFACTANT - ‘detergent’
- divides into new Type 1 and 2 cells.
(structure and support)

Question 7

Describe action of
1. β-defensins
- describe in Patients with
cystic fibrosis

Answer 7

Active against bacteria, fungi and viruses.
Bind to microbial cell membrane to form pore-like membrane defects
- Inactivate enveloped virus particles by disrupting viral envelopes or by interacting w/ viral glycoproteins(e.g. HIV gp120)
CYSTIC FIBROSIS: have extra copies of defensin genes which are more resistant to infection by Pseudomonas aeruginosa

Question 8

Describe action of
1. Surfactant protein (SP)
- name types
and describe features

Answer 8

SP-A, SP-D + C1q, Mannan Binding Lectin
Ca++ dependent, collagenous, carbohydrate (lectin) binding proteins- collectins
Bind & agglutinate pathogens
Promote phagocytosis
Modulates inflammatory response [complement?]

Question 9

Describe lung adaptive immune mechanisms:

- What Ab are produced locally in the lungs and which are transduced

Answer 9

locally: IgA/IgE (upper airway)
transuded: IgG (lower airway)

Question 10

Name parts of Lung associated lymphoid tissue

Answer 10

Hilar lymph nodes (branch of main bronchi)
Inducible Bronchus-Associated Lymphoid Tissue (BALT)
para-bronchial and para-tracheal nodes
nodules / aggregates / lymphocytes

Question 11

Effects of smoking on immunity of

1. lymphocytes
2. . neutrophils

Answer 11

1. decreased IgG, IgM, IgA and sIgA, increased IgE
   decreased functional antibody e.g. anti-flu and anti-Hep B
   reduced NK function, decreased antigen and mitogen stimulation
2. increase in neutrophil numbers
   more cells but less able to respond
   reduced chemotaxis, phagocytosis and respiratory burst
   increased peroxidase and elastase activity

Question 12

Smokers are less likely to have

Answer 12

Successful response to vaccination

• Antibody to Hong Kong A2 Flu 1968 lower in smokers
• Adverse effect of smoking on hepatitis B vaccination