Pulmonary Defense Mechanisms - Bowden Flashcards
immunological barriers at the upper airway
Anatomical barriers Cough Reflex Angulation Mucociliary apparatus airway epithelium IgA DC, N, lymphocytes
immunological barriers at the Alveolar spaces
Alveolar M (usually M2) Type 1 an dType 2 cells Clara cells (club cells) Surfactant Complement N and E
branching of the bronchi and the bronchioles causes what
more deposition of the substance
Cough Reflex
- deep inspiration
- glottis closes to trap air inside
- rise in intrathoracic P (while trying to expire)
- P buildup
- sudden release of trapped air at high P = COUGH
3 major functions of the epithelium
- barrier
- Defense towards pathogens : release of cytokines, bacteriostatic molecules
- Translocate IgA (which is in mucus and binds to pathogens)
Mucociliary Clearence
particles 2-3um to 10um get deposited in mucus (upper Airway)
Mucus has
1. IgA, lysozyme, lactoferrin, perioxidases
2. cilia on aqueous layer propelling stuff upward to be coughed or swallowed
mucus contanis what
- IgA, lysozyme, lactoferrin, perioxidases
2. cilia on aqueous layer propelling stuff upward to be
defected mucociliary clearance is present in what
Asthma
COPD
chronic bronchitis
cystic fibrosis
the airway normal has what immune cells present
Tregs (IL10, TGF-B)
DC (IL27, IL10, TGF-B)
M1 (IL10, TGF-B, IL27)
first immune cell to appear during any kind of respiratory condition
NEUTROPHILS (acute and fast and first)
what comes to the alveoli after the Neutrophil
what can they eventually do
M2 (TGF-B, IL10)
they can become smoke filled alveolar Macrophages (unable to digest what is inside) = scavenger cells
can also recruit M1
surfactant A and D function
from type 2 cells and club (Clara) cells
opsonize bacteria
activate macrophages for phagocytosis of BACTERIA
Alveolar macrophages activate what type of cells
FOX3P (Treg) cells
what is the first thing that happens during acute inflammatory response
IL1 and TNF cause IL8 to be secreted from endothelial cells + alveolar macrophages (some IL6)
this bring neutrophils
how does edema happen at the inflammatory site
plasma protiens brought into the contact of damaged area causes fluid buildup
what to the proteins at the site of damage activate
- Clotting factors : blood clot
- Complement : destroy bacteria
- Kinin cascade : vasodilation , increase permeability stimulate pain receptors
Fibroinolytic protein
degrades the blood clot when the wound is healed
Acute inflammatory response steps
- neutrophils recruited
- edema and vasodilation
- epithelium dies and sheds off
- only BM holds around alveoli
- NETs cast form neutrophils
acute inflammatory response what causes this and outcome
allergen of some sort or pathogen
if the allergen is effectively removed then all goes back to normal = fast recovery
Chronic Inflammatory response
what comes
what happens
chronic acute response causes this
- M1 and Th1, Th17, CTL come
- hypersecretion of mucus
- activate proteases
- tissue remodeling and can lead to fibrosis
ex of type 1 hypersensitivity in this lecture
Asthma
Early phase for Type 1 HS
what is brought
what happens
Acute Atopic response IgE MAST cell degranulation (IL4, IL5, Histamine) = sneezing , pruritis, rhinorrhea, congestion
Late phase for Type 1 HS
what is brought
what happens
after 4-12 hrs
N, E, B, Th2 cells*
MANY MORE MAST cells with Fce receptor
what do the eosinophils cause for chronic inflammatory response
local tissue damage and inflammation
fatigue, asthma, myalgias
what does the Eosinophils causes for remodeling
- LEUKOTRIENES C4, D4, E4 : bronchospasm, vascular permeability, mucus made
- PROSTAGLANDINS D2, E2, F2 : bronchospasm, vasodilation
= SM and fibroblasts come and deposit collagen and tissue damage
what do Th2 cells secrete for chronic inflammatory response
secretion of IL4, IL5, IL13
COPD cytokines involved
- TGF-B + IL6 causes the IL17, IL22 release
- IL17 causes
- IL8 secreted from epithelial cells
- causes N to come
- many M an dN try to get rid of the carbon smoked
smokers who dont get COPD or are immunosuppressent COPD pts with low Tregs have what kind of cells
anti-inflammatory :
TGF-B + IL2 —->
nTreg, Tr1, iTreg
SIMPLE COMPARISON BETWEEN ASTHMA AND COPD ASTHMA : 1st cells 2nd cells leading to
- Ep cells + mast cells (IL4, IL5, IL13), IgE
- Eosinophils + CD4+ Th2 cells , N
- Bronchoconstriction (and other stuff is chronic )
= reversible with inhaler)
SIMPLE COMPARISON BETWEEN ASTHMA AND COPD COPD : 1st cells 2nd cells leading to
- Avl M + Ep cells
- Neutrophils, CD8+cells
- small airway narrowing from mucus and deposition, alveolar destruction
Ventilator Associated Lung injury
happens from what
being on a ventilator causes lung damage due to
- over-inflation
- mechanical stress
- Hyper-oxygenation
- free radicals
- NEUTROPHILS COME **
Ventilator Associated Lung injury steps
- endothelium gets activated
- Neutrophils come
- Neutrophil NETs
- platelet activation
- blood clot formation
= thickening of BM and capillaries break
Vaping associated with lung injury
what is caused
what is seen
causes ARDS (Acute Respiratory Distress Syndrome)
Bilateral infiltrated on CXR
NO infection
Vaping associated with lung injury
HOW ARDS is caused
- inhlation of lipids and oils (VIT E is vaporized in the lungs to an oil
- causes lipid pneumonia
- Foam cells develop (M that take up many ipids and cant break them down)
other things causing lipid pneumonia
Essenial oils chronically used (petroleum)
Vicks, Olive oil, mineral oil
Lipid Pneumonia Tx
steroids
Antimicrobials (for secondary complications)
supportive care
