Lecture 8: Pulmonary Defense Mechanisms

Question 1

Pulmonary defense system can lead to ______ or ______

Answer 1

Recovery from disease; tissue damage (due to chronic atopic response/inflammation loop)

Question 2

What protects at the airways level?

Answer 2

Anatomical structure, mucus, cilia, IgA, innate immune cells

Question 3

What protects at the alveolar level?

Answer 3

Alveolar macrophages, Type II alveolar cells, surfactant, opsonins, complement, neutrophils, eosinophils

Question 4

What is the role of mucus and angulation in airways?

Answer 4

Traps pathogen

Angulation slows pathogen entry

Question 5

What are the steps of the cough reflex?

Answer 5

Deep inspiration > shut off glottis > increase thoracic pressure > expel air out/cough (basically an dramatic exhale)

Question 6

What is the function of airways epithelium?

Answer 6

Have cilia, adhesion molecules and TLRs
Release stuff that kill microbes
Translocate igA across airway lumen

Question 7

How does mucociliary clearance work?

Answer 7

Cilia is on the sol/aqueous layer and moves in a coordinated way to push mucus up and trigger cough reflex for pathogen expulsion

Question 8

In the absence of infection, what are immune cells doing in the airways?

Answer 8

• Tregs release IL-10 & TGF (anti-inflammation) > induces tolerance so you don’t attack everything that enters
• Dendritic cells sample the lumen and present to macrophages to detect pathogen presence

Question 9

IN the alveoli, what serves as the first line of defense?

Answer 9

Alveolar macrophages > tolerant and self renewing

Question 10

How does surfactant contribute to immunity?

Answer 10

Has SPA and D proteins that bind various pathogens. Also Acts as opsonins (defense) that does not cause inflammation (tolerance)

Question 11

In the presence of pathogen, what happens to immune cells in the airway?

Answer 11

IL-1 and TNF activated > P&E selectins, integrins activated > recruitment of leukocytes to enter area of infection

Question 12

Acute inflammation:
What molecules act as “first responders” (act in minutes)
What molecules follow later (in days)

Answer 12

Neutrophils (responds to IL-8, LFA1-ICAM1 binding on endothelium)
Macrophages (responds to CCL2 via receptor CCR2, binds to VLCAM1 on endothelium)

Question 13

What makes up the inflammatory exudates?

Answer 13

Clotting proteins
Complement
Kinin (vasodilates)
Fibrinolytic protein (lyses clots)

Question 14

How does chronic inflammatory response result in COPD?

Answer 14

Dysregulation of the inflammatory loop (doesn’t stop) continues the inflmmation. Overtime more cells go to area, more mucus secreted, tissue remodeling = fibrosis + emphysema = COPD

Question 15

What causes Type 1 hypersensitivities?

Answer 15

IgE cross linking leading to mast cell degranulation

Question 16

What is the acute atopic response and what happens during this?

What happens if there is a dysregulation of the acute atopic response?

Answer 16

Exaggerated response to pathogen. Recruitment of IL4 (recruit TH2), IL5 (recruits eosinophils), histamine (+vasodilation), leukotrienes & prostaglandins (+mucus secretion and bronchospasms) are released that end up damaging the tissue

-Upregulation of the inflammation cascade > keeps going leading to tissue damage instead of recovery

Question 17

What happens during the late phase chronic atopic response?

Answer 17

more immune cells come, more mast cells, eosinophils release helminth defense mechanisms that damage alveoli (causes CHES)

Question 18

How are leukotrienes and prostaglandins related to the development of asthma?

Answer 18

If the inflammation loop continues, overtime these remodel the airway (more fibroblasts, collagen and goblet cell deposition) = constrict the airway = asthma

Question 19

What is the main treatment for asthma?

Answer 19

Steroids (reduces inflammation)

Anti-leukotrienes (reduces mucus secretion)

Question 20

How does immune defense cause COPD?

Answer 20

if inflammation becomes chronic: TH17 > increase IL-17 & IL-22 > increase IL-8, G/GM-CSF > increase Neutrophil and macrophage recruitment > damage to alveolar walls that can eventually lead to fibrosis and emphysema

Question 21

Ventilator Associated Lung Injury

Answer 21

Hyperoxygenation > stress alveolar walls > increase free radicals > neutrophil recruitment > NETs > clotting proteins

Question 22

What characterizes VALI (vaping associated lung injury)?

Answer 22

• comes with ARDS (acute respiratory distress syndrome)

- bilateral infiltrates on CXR but no signs of infection

Question 23

What is the pathological mechanism of VALI?

How is this treated?

Answer 23

• Vaping > inhale THC with Vit. E acetate/essential oil exposure > lungs coated with lipids > foam cells in airway
• steroids and antimicrobial stuff

Question 24

Inflammation in Asthma vs. COPD
Triggers?
Reversible?
Consequences?

Answer 24

• allergens; smoking
• yes; no
• Bronchoconstriction/AHR; small airway narrowing and alveolar destruction