Pulmonary Defence Mechanisms Flashcards
What are the non specific mechanisms in the airways
Cough reflex
Mucosa traps and cilia sweeps
Antimicrobial proteins such as lysozyme
Alveolar macrophage
Functions of pulmonary macrophages
• Pulmonary homoeostasis
• Removal of cellular debris
• Immune surveillance
• Microbial clearance
• Responses to infection
• Resolution of inflammation
What does ontogeny mean
Origination and development of
2 types of Pulmonary macrophages and role
Alveolar macrophages - found in lumen of alveolus, directly exposed to air, phagocytosis of particles and catabolise surfactant to prevent collapse CD11C receptor
Interstitial macrophages - found in interstitium, remodel tissue, antigen present and prevent airway allergy CD11B receptor
What are the macrophages response to pulmonary diseases
Explain these Immune complex-mediated lung injury types
(A) Normal airways
(B) Antigen inhaled in the lung is bound by its antibody. C1q binds to antibody and activates complement cascade
(C)Lung injury can also initiate inflammation by complement activation through synthesis of complement proteins from alveolar macrophages or airway epithelium
(D)Lung inflammation is exacerbated by complement
proteins that act as chemoattractants for
neutrophils
The role of pulmonary surfactant
• Reduces the surface tension at the air–liquid interface within the alveoli of the lung
• Maintains the fluid balance in the lung, especially across the alveolar-capillary membrane
• Transports mucus and inhaled particles, impeding their adhesion in the upper airways
• Aids pulmonary innate immune response, establishes a local barrier against infection
What are the 2 groups of proteins in surfactant
Hydrophilic SP-A and SP-D
Hydrophobic SP-B and SP-C
What are the roles of SP-A and SP-D
Both SP-A and SP-D recognise, bind and clear pathogens enhancing their phagocytosis by innate immune cells such as alveolar macrophages and neutrophils
Roles of SP-B and SP-C
• SP-B and SP-C contribute to the mechanical stability of the interfacial films
• Are directly involved in the interfacial adsorption of surface-
active molecules into the air–liquid interface
• Deficiencies in, or the lack of surfactant proteins, produce severe dysfunctions in the respiratory process
• Surfactant degradation or inactivation may contribute to enhanced susceptibility to lung inflammation and infection
SP-B is especially important as total deficiency leads to death after birth
Lung epithelial lining fluid is rich is antimicrobial peptide which is important in…
Providing antiviral, antibacterial and antifungal properties
It is involved in opsonisation of bacteria and viruses by macrophages
What is the anti microbial bacteria killing mechanisms
Types of Anti microbial proteins and their mechanism of action
Lactoferin
SLPI
Lysozyme
Human defensins
Lactoferin - By binding to iron, it limits the amount of free iron for microbe growth. Inhibits biofilm formation Destabilise the outer membrane of gram-negative bacteria by binding to it.
Secretory leucoprotease inhibitor (SLPI) - Defense against destruction of pulmonary tissues by Antiviral neutrophil elastase released during degranulation at infection site. Inhibits viral DNA synthesis.
Lysozyme - Targets bacteria peptidoglycan cell wall.
Defensins - Disruption of the microbial cell membrane and metabolic disruption.
What is alpha-1 antitrypsin
• Protease inhibitor that protects lung tissues from enzymes of inflammatory cells • 0.9–2.3 g/L in blood, but the concentration can rise upon acute inflammation
• Produced in the liver and bone marrow by lymphocytic and monocytic cells in lymphoid tissue
• Dampens the effect of phagocytic enzyme elastase, reducing the damage to the surrounding lung
• Neutrophil elastase breaks down harmful bacteria, but it is potentially damaging to lungs elastin if exposed, degrading the elasticity of the lungs, which results in respiratory complications such as COPD
What conditions can arise of alpha-1 antitrypsin
• Chronic obstructive
pulmonary disease
(COPD)
• Emphysema
Most common immunoglobulin in secretions
IgA
• Forms antigen-antibody complexes
and is involved in opsonisation
• Neutralisation of pathogens by
binding to viral surface proteins that
are essential for entry of the virus into
host cells
How do T cells in COPD and cystic fibrosis lead to parenchymal lung damage
In COPD or cystic fibrosis, lung epithelial cells have reduced anion transport (Cl− and HCO3−), leading to reduced airway surface liquid (ASL) volume and reduced antimicrobial activity. This can result in persistent inflammation and chronic T cell activation and proliferation, leading to parenchymal lung damage.
