Organ-specific immunity: LUNG Flashcards
What type of branching system does the lungs have?
Dichotomous
What does the respiratory unit consist of?
The respiratory bronchioles and alveolar ducts
What do the conducting airways consist of?
Trachea, segmental bronchi and nonrespiratory bronchioles
What is found in the submucosa of the bronchus?
Cartilage and glands
What type of epithelium is that of the bronchus?
Pseudostratified
What is BALT?
Bronchus-associated lymphoid tissue
Does BALT have germinal centers?
Yes
What is the difference between BALT and lymph nodes?
LNs are more well defined and have a capsule with afferent and efferent lymphatic vessels for fluid circulation
What are club cells?
Clara cells. They are nonciliated bronchiolar secretory cells that secrete surfactants, and are progenitors for other cells
Is the beating of cilia ATP dependent?
Yes
What causes ciliary dyskinesia?
Disorder of motor proteins within cilia
What causes cystic fibrosis?
Mutations that affect chloride ion channels, preventing them from getting to the cell surface, leading to thick sticky buildup and flattening of cilia
What does ciliary dyskinesia lead to?
Mucus buildup with dirt and bateria
What influences mucus production?
DNA of damaged cells
What is a risk factor for tumorlets?
Chronic or repeated inflammation, causing consistent increase in neuroendocrine bundles aka hyperplasia
What is metaplasia?
A change of one cellular phenotype to another
What is the CTFR?
Ion transporter that regulates mucus viscosity
What does surfactant do?
Lower surface tension to be able to breathe more easily
Why is the pleura being so thin important?
Negative pressure between the lung and the thorax
Why is pulmonary infection the most common type of infection?
Exposure/interface with the environment
What is one problem with histological diagnosis of viral pneumonia?
Limited morphological specificity
What is a typical infection dynamic of viral pneumonia?
Usually self-limiting, but dominated by secondary bacterial infection in severe cases
What group is most likely to get ill from CMV infection?
Immunocompromised people
What is the definition of sarcoidosis?
A granulomatous disorder of unknown cause affecting multple organs
What organ is mostly involved in sarcoidosis?
Lungs, but generally more often organs more exposed to the air
How often do sarcoidosis patients develop progressive disease?
1/3 of patients
What surrounds granulomas?
T cells
What is the epidemiological pattern of sarcoidosis?
High rate in scandinavia but low morbidity, lower rates in other places but worse prognosis
What is the prevalence of chronic development of sarcoidosis in non-LS patients?
50%, about 20% with fibrosis
What are triggers of sarcoidosis?
Anorganic exposure, antigen exposure
What drives a granuloma?
Ongoing cytokine production by T helper cells around a trigger
What type of Th cells are present in pulmonary sarcoidosis?
Th17.1 cells
What is a biomarker of patients who develop chronic sarcoidosis?
Higher Th17.1 proportion to other Th cells
What is CTLA4?
A co-inhibitory receptor with higher affinity for CD80/CD86 than CD28
What is the CTLA4 expression level in memory Th cells in sarcoidosis, and what type of Th cells?
Reduced, Tregs and Th17
What does an increase in Th17 with reduced CTLA4 expression do?
Enhanced pro-inflammatory activity
What is double trouble in sarcoidosis?
Reduced expression of CTLA4 in Tregs (less inhibition) and Th17 (enhanced pro-inflammatory response)
What is a very pro-fibrotic cytokine?
TGFß
What drug classes are associated with sarcoid-like reaction?
Checkpoint inhibitors
What does JAK inhibition do?
Targets multiple cytokines involved in sarcoidosis, since JAK is a kinase in many pathways involved with cytokine signaling
What is the most prominent type of asthma?
Type 2 asthma
What are two ways to treat asthma?
Corticosteroids and Bronchodilators (ß2-agonists)
What do corticosteroids target?
Almost every immune cell
What do bronchodilators target?
Smooth muscle cells of the airway walls
What are two down sides to corticosteroid use against asthma?
Can cause severe side effects, and sensitivity and response is highly dependent on disease phenotype
What causes disease exacerbations in asthma?
Respiratory viral infections
What is a doenside of ß2 agonist use?
It only targets one symptom and does not treat the inflammation
What happens to tissues in chronic asthma?
Irreversible tissue remodelling, goblet cell hyperplasia
What causes the rapid constriction of the airway in asthma?
Mast cell degranulation (histamine)
What time of onset of asthma is Th2-associated and which is non-Th2 associated?
Childhood is Th2 (T2 high), usually allergy driven.
Adult is non-Th2 (T2 low), obesity and smoking associated, the later neutrophilic.
What cytokines and adaptive and innate cells does T2 high asthma involve?
IL-4, IL-5, IL-13 and IL-9, Th2 and ILC2 and honestly almost every immune cell, even B cells
What does IL-5 lead to?
Tissue eosinophilia
What does IL-4 lead to?
IgE
What do Th17 cytokines lead to in asthma?
T2 low asthma -> neutrophil recruitment
What type of asthma is characterized by neutrophilic inflammation and involved IFNy and IL-17?
T2 low
What cells are involved in T2 low asthma?
Th1, Th17, macrophages and ILC1
What type of asthma is characterized by eosinophilic inflammation, type 2 cytokines and allergen-specific B cells and IgE?
T2 high
What are alarmins?
Innate cytokines produced by epithelial cells that affect DCs and activate ILCs
What do dendritic cells do in T2 high asthma?
Take up allergen, migrate to LN, active naive T cells, which proliferate and differentiate into Th2 cells.
What are the two ways type 2 cytokine production is induced in T2 high asthma?
DCs to Th2 and alarmins to ILC2
Where are neuroendocrine cells mostly found?
Bronchioles
Where are goblet cells mainly found?
Trachea and bronchi, a bit in bronchioles
Where are submucosal glands found?
Trachea and bronchi
Where are club cells found?
Trachea, bronchi and bronchioles
What do ILC2 cells respond to?
alarmins produced by the epithelium
What cells do ILC2s interact with?
Almost everything you can think of
What is IL-13 essential for?
DC activation and migration in protease-induced allergic airway inflammation
What is a marker for activated ILC2s?
CD-45RO
What is high levels of CD-45RO+ ILC2 associated with?
Asthma severity and unresponsiveness to corticosteroids
What happens with chromatin in asthma patients?
It is open at genes encoding for ILC2
What is the cytokine production pattern of CD8 T cells in severe asthma patients?
Type 2 cytokine production by CD8 T cells is highest in severe asthma patients
