Lung infection and immunity

Question 1

What are the mechanical defences against lung infection?

Answer 1

URtract filtration
Mucociliary clearance
Coughing

Question 2

What are the local defences in lungs against infection?

Answer 2

Antiproteases and alveolar macrophages

Question 3

What is BALT?

Answer 3

(Bronchus Associated Lymphoid Tissue): samples antigens inhaled through nose and produces antibodies against these

Question 4

What is muco-ciliary clearance?

Answer 4

Cilia in the airways beat metachronally to waft mucous containing microbes towards the throat (9 microtubule pairs with dynein arms that have ATPase, providing the energy to slide over each other, using the central pair as an axis to move against)

Question 5

What is aquired Pathogenic damage?

Answer 5

Viral infections can lead to destruction of the cilia and tight junctions between epithelial cells, before opportunistic bacteria invade; cilia must regrow, taking weeks, and can regrow as useless compound cilia

Question 6

What are Microtubule abnormalities (congenital)?

Answer 6

Abnormal microtubules can lead to non-functional cilia and dextrocardia because these guide cells during embryogenesis (so if dextrocardia identified, check cilia function)

Question 7

What are Dynein arm defects (congenital)?

Answer 7

Lack of outer dynein arm prevents the cilia from moving even if present - stopping mucociliary clearance

Question 8

What is Primary ciliary dyskinesia (congenital)?

Answer 8

Lack of nasal nitric oxide appears to cause malfunctioning cilia

Question 9

What is acute pneumonia?

Answer 9

Commonly caused by Streptococcus pneumoniae, which leads to coughing, sputum, fever and dyspnoea because the alveoli become filled with pus, meaning the lung becomes solid

Question 10

What pain is associated with acute pneumonia?

Answer 10

Peripheral inflammation leads to stabbing pleuritic chest pain

Question 11

What is Bronchiectasis?

Answer 11

Chronic pneumonia:
Airways become scarred, widened and inflamed with thick mucous that the patient will struggle to clear; pockets of mucous form and harbour bacteria that can multiply without clearance leading to chronic infection

Question 12

What is the difference in ability to clear infections between acute and chronic pneumonia?

Answer 12

Acute: Airways not scarred and some effort can be made to clear infections

Chronic: Ability to clear mucous chronically damages, so cannot clear infections (easily)

Question 13

How can Bronchiectasis be managed?

Answer 13

Physio to empty the phlegm can prevent bacteria pooling and limit infection/inflammation

Question 14

What are acute and chronic pneumonia caused by?

Answer 14

Acute: Strep p.
Chronic: Bronchiectasis

Question 15

What is a chronic infection?

Answer 15

Neutrophils secrete proteases to destroy microbes during inflammation and infection, and normally this is balanced by anti-proteases in the airways; during chronic inflammation, the number of neutrophils is so large that the anti-proteases are overwhelmed leading to increased free proteases causing damage to the airway epithelia (which in turn makes it easier to be infected, creating a vicious cycle)

Question 16

What is hypersensitivity?

Answer 16

Exaggerated response to foreign substance; can be immunological or not.

Question 17

What is non-immunological hypersensitivity due to?

Answer 17

Can be due to intolerance, enzyme deficiency or pharmacologically based.

Question 18

What is Atopy?

Answer 18

Hereditary predisposition to produce IgE antibodies to common allergies, e.g. Rhinitis and Asthma
Reaction to substance in a different part of the body (atopic)

Question 19

What are hypersensitivities in different parts of the lungs called?

Answer 19

URT: Allergic rhinitis
Bronchi: Asthma
Alveoli: Allergic alveolitis

Question 20

Describe the steps in allergic rhinitis:

4

Answer 20

1. Allergens pass over epithelium in the airways and are captured by dendritic cells
2. Dendritic cells migrate to lymph nodes and stimulate TH cells to differentiate to TfH (using IL4) and TH2 cells (using IL9) that activate B-cells and mast cells respectively
3. TfH cells stimulate B-cells to become plasma cells that secrete allergen specific IgE antibodies that bind to FcE receptors on mast cells
4. When the allergen cross links IgE antibodies on mast cells, degranulation occurs leading to histamine release

Question 21

Describe the steps in Extrinsic allergic alveolitis:

3

Answer 21

1. Small allergenic particles penetrate distal airways ant enter alveoli, then interstitium
2. Particles are captured by antibodies in the interstitium to form antigen-antibody complexes
3. Complement and immunological cascades are triggered and lymphocytes are recruited

Question 22

What are the epidemiologies of allergic rhinitis and asthma?

Answer 22

Allergic rhinitis affects up to 25% of the population and asthma approx. 10%, yet the conditions are very heterogeneous and phenotypes divided by control/severity

Question 23

What is allergic rhinitis also known as…..

Answer 23

Hayfever.

Question 24

What are the aetiologies of lung hypersensitivity responses?

Answer 24

Food allergies are present from birth but chronic exposure over several seasons is needed to develop allergic rhinitis; common allergens include dust mites, pets, cockroaches, tree pollen and grass pollen

Question 25

What is the immunotherapy mechanism for treating lung hypersensitivity responses?

Answer 25

Subcutaneous/sublingual exposure to traces of the allergen leads to desensitisation because TH cells become Tregs that inhibit TfH cells, stopping the producting of IgE antibodies; they can also cause B-cells to become Bregs that inhibit B-cells or become plasma cells that produce IgG/A antibodies that compete for allergen binding with IgE, reducing the hypersensitivity response