7.3 Mechanisms of Lung Inflammation Flashcards
What are the four broad classes of substances/factors that can damage the lungs
- Microbes
- Foreign bodies
- Cell stress
- Allergens
Give some examples of types of extracellular microbes that can damage the lungs
- Bacteria
- Fungi
- Parasites
Give some examples of types of intracellular microbes that can damage the lungs
- Viruses
- Tuberculosis
A pathogen has breached the epithelial lining of the lungs. What are the types of cells that will try and defend the body, and are they adaptive or innate?
Cells such as
- Dendritic cells
- Phagocytes
- NK cells
Will come into action. They are innate.
What are defensins? Where in the barrier of the respiratory system are they located?
They are proteins located in the mucous layer of the respiratory tract. Their role is to attack and neutralise pathogens within the mucus layer
Which histological layer of the respiratory tissue do innate immune cells reside in?
Lamina propria
How do phagocytes call for backup from the adaptive immune system?
By secreting cytokines
What type(s) of innate lymphoid cells are involved in infective inflammation?
Type 1 and 3
What type(s) of innate lymphoid cells are involved in allergy?
Type 2
What are the four main pillars of innate immunity of the lungs?
- Phagocytes
- Dendritic cells
- Innate lymphoid cells
- Cytokines
How can pathogens evade the immune system of the lungs in individuals with intact immunity?
- Adherence to epithelial cells (in the case of viruses: adhering and replicating)
- Toxin release (impairs cilia function)
Describe three mechanisms by which respiratory immune defenses can be compromised
- Defective mucus (such as in CF)
- Damaged cilia (such as in smokers)
- Defects in immune cells (such as in HIV)
Outline the defences of the respiratory systyem against infection (total overview)
- Barrier: epithelial cells, with mucus and defensins in the mucus. Cilia escalate trapped pathogens up to be coughed out or swallowed
- Innate: in lamina propria, we have dendritic cells, phagocytes, innate lymphoid cells and cytokines
- Adaptive: B and T cells as usual
Broadly, what type of receptor to innate immune cells rely on to detect extracellular and intracellular pathogens?
Pattern recognition receptors
What pro-inflammatory cytokines do innate immune cells release upon recognition of a threat
- IL-6
- TNF alpha
How can acute lung inflammation lead to oedema
- Release of inflammatory mediators
- Vasodilation and increased vascular permeability of nearby capillaries
- Fluid leaks into capillaries
What is it called when fluid acutely leaks into the alveoli?
Acute respiratory distress syndrome
How is acute lung inflammation resolved after it has served its purpose?
- Cells have short half lives, and most naturally die
- Some macrophages stick around and remove alveolar debris
- Lymphatics reabsorb fluid
- Macrophages also release TNF beta to stimulate fibroblast activity (in severe cases)
- Type 2 pneumocytes proliferate to restore alveolar lining
Describe the cellular response to intracellular pathogens such as tuberculosis. How does this lead to granuloma formation?
- Pathogen is within phagocytes such as macrophages
- CD4+ T cells secrete inflammatory mediators that cause macrophages to releases reactive nitrogen intermediates and kill the pathogen
- CD8+ T cells then kill the macrophages
- Granuloma forms around necrotic cell; innermost layer is epithelial cells, surrounded by B and T cells
How can tuberculosis lead to type 4 hypersensitibity?
- After granuloma formation, T cell activity remains elevated
- Over time, this leads to a type 4 hypersensitivity reaction as a consequence of primary infection
In healthy respiratory surfaces, what is the pH range of mucus? Why?
- 5.5-6.7 (somewhat acidic)
- This creates an environment that is not conducive to bacterial growth
What are pattern recognition receptors, what is the name of the substances they detect, and what are these substances?
- Pattern recognition receptors detect Pathogen-Associated Molecular Patterns (PAMPs)
- PAMPs are nucleic acids that signal some form of infection (non-specific)
What are the two kinds of pattern recognition receptors?
- Toll Like Receptors (TLR)
- Cytosolic receptors
How can PRRs differentiate native mRNA from pathogen mRNA?
Our mRNA: methyl group at 5’ end
Foreign: no methyl cap
In what instances would cytosolic receptors interpret cytoplasmic dsRNA as a PAMP?
- All of them
- That doesn’t usually happen
Under what instances would cytosolic receptors interpret dsDNA in the cytoplasm as a PAMP
- Every instance
- This does not usually occur
Are extracellular TLRs often used to detect viral infections?
- no
- Viruses are intracellular pathogens; thus, we usually rely on endosomal TLRs to detect viral infection
At which point in DNA is it usually methylated?
CpG (Cytosine phosphate Guanine)
Name a condition which can be result in inherited mechanical compromise of the immune system
Cystic fibrosis
List some acquired conditions/substances that can lead to mechanical compromise of the respiratory immune system
- COPD
- Ethanol
- Tobacco smoke
What is the main cause of disorders of phagocytosis?
Neutropaenia (death of neutrophils)
What characterises disorders of humoral immunity?
- Decreased antibody levels
- Inability to form new antibodies
What two types of drugs can cause disorders of humoral immunity?
- Corticosteroid therapy
- Antimetabolite use
What diseases can cause disorders of cellular immunity?
- Hodgkin’s disease
- HIV/AIDS
Which age group is most susceptible to pneumonia?
Children under the age of 5
