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Module 2 > Inflammatory Cells in the Airway > Flashcards

Inflammatory Cells in the Airway Flashcards

1
Q

Describe the structure of the respiratory tract

A

NALT

Trachea

BALT

Bronchiole

Alveoli

NALT = Nasal Associated Lymphoid Tissue; BALT = Bronchus Associated Lypmhoid Tissue

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2
Q

Describe the types of cells found in and around NALT

A

Epithelial cells

M Cells

Goble tcells

Intraepithelial Lymphocytes

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3
Q

What do mature B-cells predominantly express

A

IgA

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4
Q

Where is BALT usually found and what cells are involved?

A

Lower airways at bronchiole branches

Germinal centre consisting of B-cell follicle and T-cell area interspersed with macrophages and dendritic cells

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5
Q

Compare the overall structure of NALT and BALT

A

NALT are more defined areas whereas BALT are more diffused.

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6
Q

There is a school of thought that respiratory disease occurs due to disrupted lung _____ (ie immune response vs _____ _____). Some challenges to maintenance of homeostasis include:

  • Air pressure
  • Endogenous _____ flora in lower airways
  • Inhaled _____, particulate matter and pollution

Key point: Lung immunity is a balance between maintaining homeostasis and mounting an appropriate immune response to threat

A

There is a school of thought that respiratory disease occurs due to disrupted lung homeostasis (ie immune response vs gas exchange). Some challenges to maintenance of homeostasis include:

  • Air pressure
  • Endogenous microbial flora in lower airways
  • Inhaled antigens, particulate matter and pollution

Key point: Lung immunity is a balance between maintaining homeostasis and mounting an appropriate immune response to threat

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7
Q

Describe some features of the airway epithelium that are first-line in preventing an immune response (5)

A
  • Ciliated epithelium
  • Mucus and glycocalyx
  • Tight Junctions
  • Rapid epithelial cell turnover
  • Microflora
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8
Q

Name some cells found in the large airways (conducting zone) (4)

A
  • Ciliated epithelial cells
  • Goblet Cells
  • Basal Cells
  • Neuoendocrine cells - samples for oxygen
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9
Q

Name some cells found in the small airways (3)

A
  1. Ciliated Epithelial Cells
  2. Club cells - secrete glycosaminoglycans and solution similar to surfactant
  3. Basal Cells
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10
Q

Name some cells found in the alveoli (lower airways)

A

Type I Alveolar Epithelial Cells

Type II Alveolar Epithelial Cells

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11
Q

Where is there more mucus secretion: upper or lower airways

A

Upper airways

Lower airways need less so that gas exchange is not hindered

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12
Q

Describe the function of cilia and mucus

A

Mucociliary Clearance

Ciliated epithelial cells transport mucus upwards and outwards to expell pathogens

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13
Q

What is the function of IgA when it is secreted into the mucosa

A

IgA can opsonise bacteria

Aggregation of bacteria

More phagocytosis and easier mucociliary clearance

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14
Q

Describe the structure of IgA

A
  • Can form dimers
    • J chain
    • Secretory component
  • J chain binds to IgA receptor on epithelial cells
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15
Q

How does IgA get from the lamina propria to the airway lumen

A

Trancytosis

IgA released by Plasma B cells

Dimerised with J chain

J Chain binds to IgA receptor

Endocytosis and movement of the endosome to the apical side

Secretion of IgA with a secretory component

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16
Q

Initial colonisation of airways by alveolar macrophages occurs in the first few days of birth and is dependent on fetal _____. These differentiate into macrophage subtypes depending on the environment they are in - they are referred to as _____-_____ macrophages.

A

Initial colonisation of airways by alveolar macrophages occurs in the first few days of birth and is dependent on fetal monocytes. These differentiate into macrophage subtypes depending on the environment they are in - they are referred to as tissue-resident macrophages.

17
Q

Tissue resident macrophages are involved in normal physiology as well as pathology. Give some examples of pathology.

A

Microglia - neurodegeneration

Osteoclast/blast - osteoporosis

Atherosclerosis

Kupffer cells - fibrosis

18
Q

Tissue resident macrophages are replenished throughout life through in situ _____ and self-renewal. Exposure to envrionmental factors (fibrosis, pollutants) lead to release of monocytes from the _____ _____ - these then differentiate into _____ (Ly6c+) and _____-_____ (Ly6c-). Ly6c+ differentiate into tissue resident macrophages. These cells are more _____ as they are dervied from cells produced in response to _____.

A

Tissue resident macrophages are replenished throughout life through in situ proliferation and self-renewal. Exposure to envrionmental factors (fibrosis, pollutants) lead to release of monocytes from the bone marrow - these then differentiate into circulatory (Ly6c+) and non-circulatory (Ly6c-) monocytes. Ly6c+ differentiate into tissue resident macrophages. These cells are more inflammatory as they are dervied from cells produced in response to stress.

19
Q

As we age, there is depletion of our _____-derived tissue resident macrophages. These are replensihed by _____ _____-derived monocytes, which are pro-inflammatory.

A

As we age, there is depletion of our fetal-derived tissue resident macrophages. These are replensihed by bone marrow-derived monocytes, which are pro-inflammatory.

20
Q

What are the two ‘general’ phenotypes of macrophages

A

M1 - pro-inflammatory

M2 - Tissue-healing

In reality, macrophages express same receptors but in different ratios - no distinct receptor expression

21
Q

Name some proteins produced by M2 macrophages which are involved in tissue healing

A

IL-4

IL-10

TGF-B

IGF-1

MMP-9

Arginase -> polyamines and collagen

22
Q

Name some proteins produced by M1 macrophages that are involved in inflammation

A

TNF-a

IL-6

IL-1

IFN

CXCL 9, 10, 11

23
Q

Name surface markers found on alveolar macrophages (4)

A

CD11c+

CD200R

CD206

SIGLEC-F

SIGLEC-F = Sialic Acid-Binding Immunoglobulin-like Lectin F

24
Q

Describe the process of macrophage phagocytosis

A
  1. Phagocytosis of pathogen
  2. Formation of phagosome
  3. Lysosome and phagosome fuse to make phagolysosome
  4. Pathogen degraded into fragments
  5. Antigens presented on APC surface (MHC)
  6. Leftover fragment exocytosed
25
Q

Alveolar macrophages have poor _____ _____ ability and produce _____ levels of ROS. They are naturally _____ under steady state.

A

Alveolar macrophages have poor antigen presenting ability and produce low levels of ROS. They are naturally hyporesponsive under steady state.

26
Q

Neutrophils are continuously generated in the bone marrow from myeloid precursors. Name the upstream signalling that leads to neutrophil release from bone marrow

A

Macrophage release IL-23

Th17 matures and releases IL-17A

Stimulates fibroblasts to release G-CSF

Causes release of neutrophils from bone marrow

27
Q

What two transcription factors control maturation of neutrophils

A

PU.1

C/EBP

CCAAT-enhancer-binding proteins

28
Q

Name the 6 stages of neutrophil development

A

Myeloblast

Promyelocyte

Myelocyte

Metamyelocyte

Band

Neutrophil

29
Q

Outline the process of neutrophil recruitment from the blood stream (5)

A
  1. Free circulating Neutrophil
  2. Rolling
    1. Tethering
    2. Slow Rolling
  3. Adhesion
    1. Full Arrest
    2. Firm Adhesion
  4. Crawling
  5. Transmigration
    1. Paracellular
    2. Transcellular
30
Q

Describe the process of tethering and rolling with regards to adhesion molecules involved

A

Tethers bind to endothelial P-selectin via its ligand PSGL1

PSGL1 forms patches along the whole projection that attach and pull apart sequentially - step-wise peeling of slings

Deceleration from neutrophil LFA1 to endothelial ICAM2

PSGL1 = P-selectin glycoprotein ligand 1; LFA1 = Lymphocyte function-associated antigen 1; ICAM2 = intercellular adhesion molecule 2

31
Q

Neutrophils can be short- and ‘longer’-lived. Explain the relevance as to why neutrophils can be both.

A

Short-lived

  • Limit potential to cause damage
    • Secondary necrosis
  • Die through apoptosis to protect surrounding tissue

Long-lived

  • Extended life span to ensure pathogens are cleared
  • Enables orchestration/regulation of other aspects of inflammatory response
32
Q

How can neutrophils kill pathogens (bacteria)

A
  1. ROS
    1. NADPH oxygenase-dependent mechanism (NOX)
  2. Anti-bacterial proteins
    1. Cathepsins
    2. Defensins
    3. Lactoferrin
    4. Lysosyme
  3. NETs
    1. Genetic material trapping pathogens
33
Q

NETs are composed of _____ and granule proteins (serine proteases, neutrophil elastase). They trap and kill extracellular pathogens. The neutrophils sense the _____ of the pathogen and release NETs if they are too big.

A

NETs are composed of chromatin and granule proteins (serine proteases, neutrophil elastase). They trap and kill extracellular pathogens. The neutrophils sense the size of the pathogen and release NETs if they are too big.

34
Q

Neutrophils don’t just kill pathogens, they also have _____ activity, producing pro-inflmmatory, anti-inflammatory, immunoregulatory, angiogenic and fibrogenic cytokines

A

Neutrophils don’t just kill pathogens, they also have biosynthetic activity, producing pro-inflmmatory, anti-inflammatory, immunoregulatory, angiogenic and fibrogenic cytokines

35
Q

What do neutrophils produce to activate NK cells during infection

A

IL-12 (DC), IL-18 (neutrophils)

Stimulates NK cell IFN-γ produciton

36
Q

Neutrophils can present antigens to _____ cells, promoting their maturation and capacity to mediate T cell proliferation and polarisation. Neutrophils also release chemokines to promote T cell (_____ and _____) recruitment. Neutrophils can also facilitate T cell-independent anitbody response by marginal zone B cells

A

Neutrophils can present antigens to dendritic cells, promoting their maturation and capacity to mediate T cell proliferation and polarisation. Neutrophils also release chemokines to promote T cell (Th1 and Th17) recruitment. Neutrophils can also facilitate T cell-independent anitbody response by marginal zone B cells

37
Q

Neutrophils are also _____-_____, producing _____ and pro-resolving lipid mediators. They can also negatigvely regulate T cell function.

A

Neutrophils are also anti-inflammatory, producing IL-10 and pro-resolving lipid mediators. They can also negatigvely regulate T cell function.

Module 2 (18 decks)

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