7 - Pulmonary Defense Mechanisms

Question 1

The lung is continuously exposed to the outside environment. Defense mechanisms are necessary to ensure efficient _______ _______ and prevent ________.

Answer 1

Gas exchange

Infection

Question 2

Lung defense can be divided into two locations, which are…

Answer 2

Upper airways and bronchi

Alveolar spaces

Question 3

The first defense of the upper airways and bronchi is the removal of particulate matter. Describe which sizes of particulate matter are removed where.

Answer 3

Particle size > 10 um = Removed by tonsils and adenoids

Particle size 2-10 um = Removed by mucokinesis and coughing

Particle size <2 um = Makes it to lungs

Question 4

What are the steps of the cough reflex?

Answer 4

1) Deep inspiration
2) Trapping of air by shutting off its exit (glottis in the case of cough)
3) Initiation of expiratory effort, raising the intrathoracic pressure
4) Buildup of pressure
5) Sudden release of the trapped air at high pressure

***Cough can be triggered by chemicals, mechanical stimulation, inflammation, or be voluntary

Question 5

This has a barrier function and a defense function. It releases bacteriostatic molecules and regulates an immune response containing receptors and producing cytokines. Supports microbiome.

Answer 5

Airway Epithelium

Question 6

Airway epithelium translocates…

Answer 6

IgA

Question 7

Particles larger than 2-3 um and smaller than 10 um are deposited on the mucus of the upper airways. The mucus contains defense molecules…

Answer 7

IgA
Lysozyme
Lactoferrin
Peroxidases

Question 8

What is the mucus blanket composed of?

Answer 8

Sol Layer – aqueous

Mucus Layer

Question 9

Cilia move through the Sol Layer striking the Mucus Layer above and propel it forward (mucus elevator). This is called _________ __________. This mechanism is altered in disease states such as asthma, chronic bronchitis, and cystic fibrosis.

Answer 9

Mucociliary Clearance

Question 10

These are the first line of defense in the alveoli. They are tissue residents, and are long-lived and self-renewing.

Answer 10

Alveolar (Airway) Macrophages

Question 11

These proteins are synthesized by Type II Alveolar and Clara cells. They bind to a wide range of pathogens, suppress microbial growth, damage bacterial membranes, and modulate macrophage phagocytosis.

Answer 11

Surfactant Protein A (SP-A)

Surfactant Protein D (SP-D)

Question 12

What is the acute immune response?

Answer 12

– Activation of immune response by exogenous triggers

– Influx of inflammatory cells from capillaries into air spaces

– Deployment of neutrophil nets

Question 13

______ and ______ increase expression of P & E Selectins on endothelium (1-2 hours), binds, detaches, binds, “rolling” of leukocyte. End result is the leukocytes slow down.

Answer 13

IL-1

TNF

Question 14

Slowing down of leukocytes allows cells to respond to chemokines in the area that are produced in response to ______ and ______. Chemokines increase affinity and clustering of integrins for ligand binding. The leukocytes firmly attach, cytoskeleton reorganizes and they flatten on endothelium.

Answer 14

TNF

IL-1

Question 15

This occurs when plasma proteins come in intimate contact with the damaged area. Due to inflammatory exudate.

Answer 15

Edema

Question 16

What are the proteins in the inflammatory exudate?

Answer 16

Clotting Proteins
Complement
Kinin Cascade
Fibrinolytic Protein

Question 17

These proteins form blood clots to prevent further loss of blood.

Answer 17

Clotting Proteins

Question 18

These proteins stimulate immune responses and destroy bacteria.

Answer 18

Complement

Question 19

These proteins cause vasodilation and increase the permeability of blood vessels and stimulate pain receptors.

Answer 19

Kinin Cascade

Question 20

This protein degrades the clot when the wound has healed.

Answer 20

Fibrinolytic Protein

Question 21

A chronic inflammatory response develops over time due to infiltration of activated ________ and ________. There is mucus hypersecretion and substantial remodeling of tissue leading to fibrosis.

Answer 21

T Cells

M1 Macrophages

Question 22

What can occur in an early phase (immediate) acute atopic response?

Answer 22

In minutes:

• • Cross-linking of mIgE
• • Degranulation of Mast cells
• • Sneezing, pruritus, rhinorrhea, congestion
• • Preformed Mast cell cytokines and inflammatory proteins recruit inflammatory cells to the area

Question 23

What can occur in late phase chronic atopic response?

Answer 23

Hours 4-12:

– Influx and activation of eosinophils, neutrophils, basophils, and lymphocytes (Th2)

– 10-fold increase in Mast cells present in area

– Increased expression of Fce receptors

– Systemic symptoms: fatigue, myalgias, asthma

Question 24

In chronic asthma related airway remodeling, these induce bronchospasm, vascular permeability, and mucus production.

Answer 24

Leukotrienes C4, D4, and E4

Question 25

In chronic asthma related airway remodeling, these induce bronchospasm and vasodilation.

Answer 25

Prostaglandins D2, E2, and F2

Question 26

In chronic asthma related airway remodeling, the recruitment of smooth muscle cells and fibroblasts lead to deposit of _________ in the submucosa.

Answer 26

Collagen

Question 27

There is _______ mediated inflammation in COPD. These cytokines induce IL-8 and G/GM-CSF secretion from airway epithelial cells (IL-17, IL-22).

Answer 27

Th17

Question 28

In COPD there is recruitment of large population of inflammatory…

Answer 28

Macrophages and Neutrophils

Question 29

Is Asthma or COPD being described?

• • Allergens
• • Epithelial cells
• • Mast cells
• • CD4+ cell (Th2)
• • Eosinophil
• • Bronchoconstriction

Answer 29

Asthma

Question 30

Is Asthma or COPD being described?

• • Cigarette Smoke
• • Alveolar Macrophages
• • Epithelial cells
• • CD8+ cell (Tc1)
• • Neutrophils
• • Th17
• • Small airway narrowing and alveolar destruction

Answer 30

COPD

Question 31

What type of lung injury is being described?

Physical Damage:

• • Over-inflation
• • Mechanical stress

Biodamage:

• • Hyper-oxygenation
• • Free radical production
• • Influx of neutrophils into tissue from activation of endothelium
• • Neutrophil netosis leading to platelet activation and clot formation

Answer 31

Ventilator Associated Lung Injury

Question 32

This type of injury is present with ARDS and has bilateral infiltrates on CXR. There is absence of infection. If vaping was used within last 90 days then there is no other plausible cause.

Answer 32

Vaping Associated Lung Injury (VALI)

Question 33

This type of pneumonia is caused by inhalation/aspiration of lipids. It is usually very rare. There can be a dramatic increase due to vaping CBD/THC and the use of essential oils in large quantities.

Answer 33

Lipoid Pneumonia