Immunology of Interstitial Lung Diseases Flashcards
Pulmonary Defense Mechanisms
- The lung is continuously exposed to the outside environment
- Defense mechanisms are necessary to ensure efficient gas exchange and prevent infection
- Removal mechanisms are aimed at minimizing inflammation
Lung defense can be divided into two locations
- Upper airways and bronchi
- Host defenses in alveolar spaces
Lung defense can be divided into two locations
Upper airways and bronchi
•Upper airways and bronchi
–Anatomic barriers
–Cough
–Mucociliary apparatus
–Airway epithelium
–Secretory IgA
–Dendritic cells, lymphocytes, neutrophils
Lung defense can be divided into two locations
Host defenses in alveolar spaces
•Host defenses in alveolar spaces
–Alveolar macrophages
–Immunoglobulins, opsonins, and surfactants
–Lymphocyte-mediated immunity
–Neutrophils and eosinophils
Scanning Electron Micrograph of Cilia
Overview of the Immune Cells in the Pulmonary Immune System
BALT and GALT
Immunology of Interstitial Lung Disease- Objectives
- Given a case presentation, identify the specific ILD.
- For each ILD listed in this presentation describe the associated immune response when known.
- Contrast the characteristic immune responses for IPF, sarcoidosis, and HP.
Interstitial and Inflammatory Lung Diseases (ILD)
- Idiopathic interstitial pneumonias
- Connective tissue diseases
- Systemic sarcoidosis
- Hypersensitivity pneumonitis
- Eosinophilic lung disease
BAL Apparatus
Pulmonary Diseases
BAL from a Scleroderma Patient
Classification of Idiopathic Interstitial Pneumonias
Idiopathic Interstitial Pneumonias
- Heterogeneous group with similar clinical findings and fibrosing in nature
- BAL findings are used to exclude infection, tumor, asbestosis, or other specific diseases
- Effectiveness of corticosteroids depends on the disease
–In idiopathic pulmonary fibrosis (IPF) use of corticosteroids is not indicated
–Nonspecific interstitial pneumonia (NSIP) has a more favorable response to corticosteroids
SEM of Transection of Pulmonary Capillary
Alv: alveolus
EP: alveolar epithelium
IN: interstitial space
BM: basement membrane
EN: capillary endothelial cell
C: capillary
FB: fibroblast
Events in the Development of IPF
TGF-β: normal action is cell-type and context-dependent and includes anti-inflammatory and tissue repair promotion. TGF-β is also anti-proliferative and thought to promote epithelial-mesenchymal transition. Chronic expression of TGF-β has been shown to play a role in tissue fibrosis. In IPF the origin of TGF-β is postulated to be alveolar macrophages.
Source of myofibroblasts: epithelial-mesenchymal transition, mesothelial-mesenchymal transition, local mesenchymal cells, and circulating progenitor cells- all are considered to be a potential source but more research is needed to definitely show the source of increased myofibroblasts in the lungs of IPF patients
Mediators of Fibrosis: Inulin-like growth factor binding protein (IGFBP)5 has been shown to be associated with increased fibrosis. Additionally increased expression of the vasoconstrictors endothelin 1 (ET-1 and angiotensin II has been associated with increased fibroblast activation. Research literature indicates ACE inhibitors are protective against radiation-induced lung fibrosis.
Evidence for the Role of Cellular and Humoral Immunity in IPF
- Involvement of CD4+ T cells (activated phenotype)
- Biased T cell receptor Vβ repertories (BAL and peripheral)
- Presence of autoantibodies in some studies with IPF patients
- Evidence of lymphoid neogenesis without organized structure
Connective Tissue Diseases
- Rheumatoid arthritis (RA)
- Systemic lupus erythematosus (SLE)
- Sjögren syndrome
- Systemic sclerosis (SSc)
- Pulmonary manifestations include ILD
- Mechanism?
Genetic Contribution to IPF
- Wang Y, Kuan PJ, Xing C, et. al. Genetic defects in surfactant protein A2 are associated with pulmonary fibrosis and lung caner. Am J Hum Genet 2009; 84: 52-9.
- Nogee LM, Dunbar AE III, Wert SE, Askin F, Hamvas A, Whitsett JA. A mutation in the surfactant protein C gene associated with familial interstitial lung disease. N Engl J Med 2001; 344: 573-9.
- Armanios MY, Chen JJ, Cogan JD, et al. Telomerase mutations in families with idiopathic pulmonary fibrosis. N Engl J Med 2007; 356: 1317-26.
- Seibold MA, Wise AL, Speer MC, et. al. A common MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med 2011; 364: 1503-12.
Percentage of Subjects with ILD and RA- Correlation to Smoking
Systemic Sarcoidosis
- Multisystem granulomatous
- Noncaseating epithelioid granulomas
- Depression of DTH responses
- Interstitial pneumonitis and granulomatous formation can progress to fibrosis with loss of alveolar and bronchial tissue and vascular surface area
Inflammatory Response in Sarcoidosis
Persistent Granulomatous Inflammation
- Persistence of antigen
- Failure of the immune system to halt inflammatory processes
Hypersensitivity Pneumonitis (HP)
- Group of lung diseases caused by inhalation of exogenous antigenic molecules (usually organic)
- Transient fever, hypoxemia, myalgias, arthralgias, dyspnea, cough 2-9 hr after exposure
- Symptoms resolve without treatment provided there is no re-exposure to antigen
