Pulmonary Defense Mechanisms Flashcards
What are the three main defense mechanisms?
1) Configuration of naropharynx and airway branching
2) Mucociliary clearance and cough
3) Alveolar clearance
How does airway configuration protect the system?
Promotes particle deposition proximally before vulnerable alveolar structures.
What is seen as harmful by the innate immune system?
Any large particle
What is airway epithelial fluid?
Antimicrobial peptides and proteins, antioxidants, antiproteases, IgA, low pH.
*Hypersecretion in disease states
What factors impair cilia?
Air pollution, viral infection, cigarette smoke, genetic conditions (Kartageners-primary ciliary dyskinesia)
What factors does the immune system use to determine what particles could be harmful?
Size and physiochemical property discrimination
PAMPs
Recognition by dendritic cells
Macrophages- bronchoalveolar lavage
What is done with harmless particles?
Removed by mucociliary escalator
What is done with harmful particles?
Recognized by dendritic cells and trafficked to lymph node. DCs are primary when no PAMPs are present.
How is inflammation suppressed?
Macrophages via SIRP-alpha, binds to SP-A and SP-D.
What receptors actually recognize microbes?
Secreted pattern recognition receptors (SPRRs) and cellular pattern recognition receptors (CPRRs)
SPRRs bridge PAMPs and specific receptors (SP-A, SP-D, complement, CRP, amyloid)
CPRRs sense PAMPs in extracellular, endosomal, and cytoplasmic compartments.
What changes occur when a PAMP is present?
Epithelial cells express chemokines to recruit neutrophils. DCs stimulate T cell proliferation and macrophages induce inflammation from SP-A and SP-D binding. Neutrophils injest pathogens.
What are the two functions of macrophages in the lungs?
1) Suppress pro-inflammatory adaptive response when not appropriate and induce repair instead
2) Generate harmful inflammation that leads to fibrosis
