Pulmonary Defense Mechanisms

Question 1

What are the two divisions of lung defense?

Answer 1

upper airways and bronchi

alveolar spaces

Question 2

What are the defense mechanisms of the upper airway and bronchi?

Answer 2

Anatomic barriers

angulation

cough reflex

mucociliary apparatus

airway epithelium

secretory IgA

dendritic cells, lymphocytes, neutrophils

Question 3

What are the defense mechanisms of the alveolar spaces?

Answer 3

alveolar macrophages

type II alveolar cell

surfactants and opsonins

complement pathways

neutrophils and eosinophils

Question 4

What is the sequence of events for the cough reflex?

Answer 4

1. deep inspiration
2. trapping of air by shutting off its exit (glottis)
3. initiation of expiratory effort, raising intrathoracic pressure
4. build up of pressure
5. sudden release of trapped air at a high pressure

*TRIGGERED* by checmicals, mechanical stim, inflammation, or voluntary action

Question 5

What are the defense functions of the airway epithelium?

Answer 5

release bacteriostatic molecules

regulate immune response with receptors/cytokines

support microbiome

Epithelium also works as a barrier and can translocate IgA

Question 6

Describe mucociliary clearance

Answer 6

particles between 2-10um are deposited on the mucous membranes of the upper airway

mucous contains IgA, lysozyme, lactoferrin and peroxidases

the mucous membrane is two layers: sol (aq) and mucous

the cilia move through the sol layer striking the mucous layer above and propel the particles forward, geting them stuck in the mucous

* this process is altered in asthma, chronic bronchitits, and CF *

Question 7

What are some other immunological defenses in the airways?

Answer 7

lymphoctes (submucosal and intraepithelial)

Club cells (clara)

dendritic cells

cytokines

lots of Tregs

Question 8

what cell type is the first line of defense in the alveoli?

Answer 8

Macrophages

reside in tissue

long lived, self renewing

plastic responses-usually M2, help maintain tolerance

Question 9

What is the role of surfactant?

Answer 9

made by type II pneumocytes and Club cells, there is SP A and SP D that both bind and supress pathogens and microbial growth, damage bacterial mebranes, and modulate macrophage phagocytosis

Question 10

What immunoglobulins are present in the alveolar space?

What non-immune opsonins are present in the alveolar space?

Answer 10

IgA and IgG

surfactant, fibronectin, MBL, CRP

Question 11

How is tolerance maintained in the airway?

Answer 11

anti-inflammatory environment of the pulmonary tissues as well as support from the microbiome

Question 12

After inflammation of the pulmonary tissue, how is the tissue recovered?

Answer 12

activation of normal immune response and subsequent tissue repair by

1. cell proliferation and regeneration
2. revascularization
3. tissue remodeling

Question 13

What are the main events of an acute immune response in the lungs?

Answer 13

activation of immune responses by exogenous triggers

influx of inflammatory cells from capillaries into air spaces

deployment of neutrophil nets

recruitement of leukocytes

formation of exudate

Question 14

How are leukocytes recruited to the site of infection?

Answer 14

IL1 and TNF increase expression of P and E selectins on endothelium within the first 2 hours

these “roll” on the endothelium by binding and releasing continuously until the leukocytes slow down

once they slow down, they respond to chemokines in the area produced by TNF and IL1

chemokines increase affinity and clustering of integrins for ligand binding

leukocytes attach, flatten and squeeze through endothelium into tissue

Question 15

What chemokine/cytokines are involved in neutrophil recruitment in the first few hours?

What chemokine/cytokines are involved in macrophage recruitment in the first few days?

Answer 15

LFA1-ICAM1

IL8-IL8L

VLA4-VCAM1

CCR2-CCL2

Question 16

Formation of inflammatory exudate starts with

Answer 16

edema which brings plasma proteins into intimate contact with the damaged area

Question 17

proteins in the inflammatory exudate include

Answer 17

• clotting proteins: prevents further blood loss
• complement: destroys bacteria
• kinin: vasodilate, stimulates pain
• fibrinolytic protein: degrades clot after healing

Question 18

Over time, a chronic inflammatory response can be triggered by the following:

Answer 18

infiltration of activated T cells and M1 macrophages

mucus hypersecretion

substantial remodeling of tissues leading to fibrosis

Question 19

instead of the normal tissue recovery that was in a previous FC, during chronic inflammation, what happens?

Answer 19

dysregulation of the inflammatory cascade leading to tissue injury and disease

Question 20

Within minutes, what occurs in a type I hypersensitivty reaction?

Answer 20

cross linking of mIgE

degranulation of mast cells

sneezing, pruritis, rhinorrhea/congestion

preformed mast cell cytokines and inflammatory proteins recruit inflammatory cells to the area

Question 21

Within 4-12 hours, what occurs in the type I hypersensitivity respinse?

Answer 21

influx and activation of eosinophils, neutrophils, basophils and Th2 lymphocytes

10x increase in mast cells with increased Fce receptors

systemic sx of fatigue, myalgias, asthma

Question 22

What are eosinophils?

Answer 22

proinflammatory mediators

leading to local tissue damage, sinus infections

can cause chronic hyperplastic eosinophilic sinusitis

Question 23

How does airway remodeling occur in chronic asthma?

Answer 23

Leukotrienes C4, D4 and E4 induce bronchospams, vascular permeability and mucus production

Prostaglandins D2, E2, F2 induce bronchospasm and vasodilation

recruitment of Smooth Muscle cells and fibroblast lead to deposition of collagen in submucosa (leading to remodeling)

Question 24

treatment and MOA for anaphylaxis

Answer 24

Epinephrine

causes vascular smooth muscle cell contraction, increasing cardiac output to counter shock and inhibits bronchial smooth muscle cell contraciton

Question 25

What is the treatment and MOA for bronchial asthma?

Answer 25

corticosteroids, reduce inflammation

leukotriene antagonists: relax bronchial smooth muscle and reduce inflammation

phosphodiesterase inhibitors: relax bronchial smooth muscles

Question 26

What are the treatmetns and MOAs for various allergic diseases?

Answer 26

desensitization: may inhibit IgE production, or induce T cell tolerance

Anti-IgE ab: neutralizes and eliminates IgE

Antihistamines: block actions of histamines on vessels and SM. M.

Cromolyn: inhibits mast cell degranulation

Question 27

What is Th17 mediated inflammation in COPD?

Answer 27

Th17 cytokines induce IL8 and G/GM-CSF secretion from airway epithelial cells (IL 17 and 22)

this causes recruitment of large population of inflammatory macrophages and neutrophils

this causes small airway narrowing and alveolar destruction that is irreversible

Question 28

What is ventilatory associated lung disease?

Answer 28

iatrogenic

causes physical damage and biodamage

Physical: over inflation and mechanical stress

Biodamage: hyperoxygenation, free radicals, increase in neutrophils into tissues from endothelial activation, increased netosis leading to platelet activation and clotting

Question 29

Vaping associated lung injury

Answer 29

presents with ARDS

bilateral infiltrates on CXR

absence of infection

Vaping use within last 90 days

no other plausible cause

26 deaths and 1300 cases at end of 2019

Question 30

Lipoid PNA

Answer 30

PNA caused by inhalation/aspiration of lipids

usually rare

seen in increase due to vaping CBD/THC or vit. E acetate as well as from essential oils: vicks, castor oil, olive oil, mineral oil, petro jelly, lip gloss

tx: supportive, steroids, antimicrobials secondary to complication.