Pulmonary Defense Mechanisms

Question 1

True or False: The lung is the largest epithelial surface in the body

Answer 1

True

Question 2

Chronic disease states can happen due to two general things. What are they?

Answer 2

1. Infection overwhelms the system (e.g. tuberculosis) 2. Pathologic responses are over exuberant and impair rather than protect the host.

Question 3

What are the 3 pulmonary defense mechanisms?

Answer 3

1. Configuration of the nasopharynx and serial branching of the airways allows for particle deposition proximal to more vulnerable alveolar structures. 2. Mucociliary clearance and cough 3. Alveolar clearance (macrophages and immune response)

Question 4

Mucus is hydrated by ____ ____

Answer 4

epithelial fluid

Question 5

What are constituents of airway epithelial fluid that help with defense, maintanance of structure and function?

Answer 5

1. Antimicrobial peptides and proteins (e.g. B-defensins, cathelicidin, lysozyme, and lactoferrin)
2. Antioxidants (glutathione)
3. Antiproteases
4. IgA
5. Decreased pH

Question 6

____ of mucus plays an important role in the pathophysiologic characteristics of various chronic airway diseases

Answer 6

Hypersecretion

Question 7

What are 3 things that can reduce ciliary function?

Answer 7

1. air pollution
2. viral infection
3. smoking

Question 8

What is the genetic disorder associated with abnormal ciliary function?

Answer 8

Primary ciliary dyskinesia (immotile ciliary syndrome)

• autosomal recessive
• due to defects in dynein arms (a motor control protein that helps with cytoskeleton movement of cilia)
• these patients have sinusitis, bronchiectasis, situs inversus (mirrored organs), and pneumonia
• Kartagener’s syndrome which is a combination of situs inversus, chronic sinusitis, and bronchiectasis.

Question 9

True or False: The hydration of mucus is very important.

Answer 9

True. CF patients are unable to properly hydrate their mucus so it gets thick and difficult to move.

Question 10

What is a common feature of cystic fibrosis, chronic bronchitis, and asthma?

A. Dysfunctional cilia

B. Increased mucus secretion

C. Defects in ion transport

D. Caused by smoking

Answer 10

B. Increased mucus secretion

Question 11

What do dendritic cells do in the defense mechanism?

Answer 11

They traffic inhaled particles to local lymph nodes to promote tolerance to common antigens

Question 12

What’s the cell breakdown in a normal person’s alveolar air spaces?

Answer 12

Macrophages (90-95%)

Lymphocytes (less than 5%)

Eosinophils (less than 1 %)

Neutrophils (less than 1 %)

Question 13

Smokers have a dramatic ____ in the number of alveolar macrophages

Answer 13

Increase

Question 14

Which of the following is the predominant cell type in the bronchoalveolar lavage of normal subjects?

A. lymphocytes

B. macrophages

C. neutrophils

D. eosinophils

Answer 14

B) Macrophages

Question 15

In the absence of PAMPS, what happens to inhaled particles?

Answer 15

Particles are taken in by dendritic cells and taken to local lymph nodes to promote tolerance to common antigens. In the alveolar spaces, macrophages take up the inhaled particles to try to maintain an anti-inflammatory state.

Question 16

How is inflammation suppressed in the absence of PAMPs?

Answer 16

Inflammation is suppressed through the tonic signaling of resident alveolar macrophages via SIRPalpha (signal inhibitory regulatory protein).

Surfactant proteins A and D (a.k.a. collectins) bind to SIRPalpha which blocks downstream signaling cascade of inflammation.

Question 17

What are secreted pattern recognition receptors?

Answer 17

They serve as bridges between PAMPs and their specific receptors.

This includes collectins (SP-A, SP-D), complement (recognizes Fc region on IgG and IgM antibodies–promotes opsonization of microbes), and pentraxins (c-reactive protein, serum amyloid)

Question 18

What are cellular pattern recognition receptors? Name 3 categories

Answer 18

These sense PAMPs in extracellular, endosomal, and cytoplasmic compartments.

1. Toll-like receptors (Expressed on epithelial cells, macrophages, PMNs and dendritic cells)
2. Scavenger receptors (CD36, CD206)
3. C-type lectin receptors (recognize high density carbohydrate based PAMPs)

Question 19

What happens when PAMPs are present in inhaled material?

Answer 19

• Activation of innate immunity
• Stimulation of epithelial cells to express chemokines, cytokines, and lipid mediators
• Recruitment of neutrophils
• Dendritic cells traffic to lymph nodes and stimulate T-cell proliferation
• Alveolar macrophages initiate inflammation

Question 20

What do SP-A and SP-D in presence of PAMPs?

Answer 20

Instead of being bound to the inhibitory proteins, SP-A and SP-D are secreted and bind to microbial PAMPs leading to opsonization and phagocytosis by alveolar macrophages and dendritic cells. They also initiate the inflammatory response.

Question 21

What is a common chemotactic factor that attracts neutrophils?

Answer 21

IL-8

Question 22

In an inflammatory response, how are neutrophils attracted to the lung?

Answer 22

Alveolar macrophages and epithelium release IL-8 which recruits neutrophils.

Question 23

What do neutrophils do once they arrive in the lung?

Answer 23

They ingest bacteria and fungi that have been opsonized by complement. They kill by oxidant production, microbial-cidal proteins, and extracellular traps

Question 24

Macrophages perform many different roles in pulmonary defense. Name 4 roles

Answer 24

1. Suppression of pro-inflammatory adaptive immune responses (when no PAMPs are around)
2. Clearance of particles, pathogens, apoptotic cells, and cellular debris
3. Elicit an inflammatory response when appropriate (presence of PAMPs)
4. Induction of tissue repair

Question 25

True or False: You are born with resident macrophages in your lung that developed from the yolk sac and liver.

Answer 25

True. During inflammation, the level of resident macrophages remains steady while the number of macrophages increases and decreases based on the monocytes being recruited to enter from the blood stream (bone marrow macrophages)

Question 26

Inflammation in the lungs is started by ___ macrophages

Answer 26

Resident. They release IL-8 and other stuff to recruit the bone-marrow macrophages.

Question 27

True or False: During an inflammatory response, monocytes turn into different kinds of macrophages depending on the kind of chemotactic factors present.

Answer 27

True

Question 28

\_\_\_\_ programmed macrophages can generate inflammation that can be harmful. Name 3 diseases that these macrophages are present in.

Answer 28

alternatively 1. Sarcoidosis 2. lung cancer 3. pulmonary fibrosis

Question 29

What 3 things happen in resolution of defense?

Answer 29

1. Removal of the foreign agent 2. Reversal of the inflammatory process (e.g. the inflammatory mediators) 3. Removal of the inflammatory cells and debris

Question 30

What are the 4 outcomes of resolution?

Answer 30

Resolution - migration, replication, and differentiation of parenchymal cells on a msotly intact matrix framework. Destruction - irreparable tissue damage (leaving open space) Scarring - fibroblast accumulation and deposition of collagen with permanently impaired tissue structure and function Chronic inflammation

Question 31

What cell type initiated the adaptive immune response and what happens in the adaptive immune response?

Answer 31

Dendritic cells initiate the adaptive immune response when the sense PAMPs. Adaptive immune response: B and T cells Provides antigen specificity Upon re-exposure, immunological memory allows for a more rapid and augmented secondary immune response.

Question 32

What are 3 things that can alter defense responses?

Answer 32

1. Cigarette smoking (increased alveolar macrophages) 2. Alcoholism (decreased mucociliary clearance, impaired epithelial cell macrophage and T cell functions) 3. Air polution