Host defense mechanism of the lungs

Question 1

What are some of the mechanisms that exist to prevent excessive inflammation on the lungs?

Answer 1

Decreased expression of pattern recognition receptors, surfactant proteins which modulate the immune response, and “don’t eat me” molecules, most prominently CD200

Question 2

What are the claudins implicated in maintaining respiratory epithelium tight and adherens junctions?

Answer 2

Cld3, cld4, and cld18.

Question 3

What are some of the innate defense substances secreted by respiratory epithelia?

Answer 3

Beta-defensins, surfactant proteins, mucins, lactoferrin, and lysozymes.

Question 4

What does the presence of sialic acid on mucins allow them to do?

Answer 4

Sialic acid on glycans bind soluble effector molecules (such as IgA and beta-defensins).

Question 5

What are the most common mucins in the airways?

Answer 5

MUC5A and MUC5B. Deficiencies in either have been implicated in bacterial infections.

Question 6

What is primary ciliary dyskinesia (PCD)?

Answer 6

A collection of clinical presentations associated with cilia motility dysfunction.

Question 7

What class of innate defense molecules do the surfactant proteins SP-A and SP-D belong to?

Answer 7

They are collectins, just like C1q and MBL from the complement cascade.

Question 8

What is tubular myelin?

Answer 8

Lattice-like arrays of intersecting membranes that serve as an extracellular reservoir for surfactant proteins and lipids.

Question 9

What is required for the formation of tubular myelin?

Answer 9

SP-A and SP-B are required for the formation of tubular myelin.

Question 10

What are some examples of substances hosted within tubular myelin?

Answer 10

SP-B and SP-C (required for sufactant function), as well as lysozymes and other innate defense molecules.

Question 11

How can commensal organisms influence respiratory immunity?

Answer 11

The types and abundance of bacterial and fungal species can deferentially influence immune responses triggered by pathogens.

Question 12

How does the respiratory tract respond to commensal organisms?

Answer 12

Inflammation in response to these organisms is tightly controlled, and a basal level of activation (through PRR stimulation) is maintained on the epithelia.

Question 13

What are some cell types in the respiratory tract that express PRRs?

Answer 13

Conducting airway cells and both type I and II alveolar cells express many TLRs and NLRs (Nod1 and Nod2).

Question 14

Where are dendritic cells (DC) located in the respiratory epithelium?

Answer 14

On the basolateral side.

Question 15

What are the three subsets of lung dendritic cells?

Answer 15

CD11c high CD103+, CD11c high CD11b+, and CD11c intermediate PDCA-1 high.

Question 16

What do CD103+ (CD11c high) dendritic cells assist with?

Answer 16

Anti-viral responses of CD8 cells. They posses very efficient MHC loading machinery and cross-presentation capabilities.

Question 17

What do CD11b+ (CD11c high) dendritic cells assist with?

Answer 17

They induce central memory CD8 and CD4 T cells.

Question 18

What are CD11c intermediate (PDCA-1 high) dendritic cells?

Answer 18

They are plasmacytoid DC that produce large amounts of type I interferons (anti-viral). They also help to maintain tolerance to harmless antigens.

Question 19

What are the three types of lung macrophages?

Answer 19

Bronchial, interstitial, and alveolar.

Question 20

How can alveolar macrophages induce tolerance?

Answer 20

Alveolar macrophages can inhibit inflammatory responses by inhibiting DC mediated T cell activation, producing TGF-beta, and generating other cytokines involved in T-reg differentiation.

Question 21

How do alveolar epithelial cells (AEC) assist alveolar macrophages with maintaining tolerogenicity?

Answer 21

They produce IL-10, and activate inactive TGF-beta produced by alveolar macrophages. Alveolar epithelia also express CD200, which interacts with CD200R to inhibit IL-2 secretion and promote anti-inflammatory cytokine production (IL-10, ect).

Question 22

How does infection override the inhibitory responses in the lungs?

Answer 22

The negative signals of the inhibitory receptors are overridden during infection through the activation/ligation of many PRRs (TLRs, NLRs, scavenger receptors)

Question 23

How are alveolar macrophages affected during infection?

Answer 23

During infection, alveolar macrophages are signaled to up-regulate potent phagocytic activity. This is promoted by SP-A and SP-D.

Question 24

Where are virus-specific B cell responses generated in the respiratory tract?

Answer 24

The regional draining lymph nodes or the MALT of the bronchi or nose.

Question 25

What is the dominant antibody isotype in the respiratory tract?

Answer 25

IgG (surprisingly not dimeric IgA).

Question 26

Where else is IgG the prominent Ab isotype in mucosal secretions?

Answer 26

Both female and male urogenitary tracts.

Question 27

Can all antibody isotypes be found to some extent in mucosal secretions?

Answer 27

Yes. For example, IgE can be transported across epithelial cells as well through the FCeRIII receptor.

Question 28

What cells determine the outcome of B cell humoral responses?

Answer 28

Tfh cells. They express CXCR5 and produce IL-21.

Question 29

What is a unique subset of memory T cells that can ensure rapid responses to reinfection?

Answer 29

Resident memory T cells (Trm). They are CD69+ (stay in the LN) cells that are restricted to certain tissue types, and they can quickly exhibit effector functions for rapid responses.

Question 30

Where do resident memory T cells reside?

Answer 30

They reside in mucosal lymphocyte clusters (MLCs)

Question 31

As a review, what are the surface markers of central and effector memory T cells?

Answer 31

Central memory cells are CD62 high (enter lymphatics) while effector memory cells are CD62 low (stay in periphery).