Immunology of Interstitial Lung Diseases Flashcards
Immunology of Interstitial Lung Diseases
- 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
–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
–Alveolar macrophages
–Immunoglobulins, opsonins, and surfactants
–Lymphocyte-mediated immunity
–Neutrophils and eosinophils
Interstitial and Inflammatory Lung Diseases (ILD)
- Idiopathic interstitial pneumonias
- Connective tissue diseases
- Systemic sarcoidosis
- Hypersensitivity pneumonitis
- Eosinophilic lung disease
Diagnostic morphologic changes in BAL fluids
Normal:
Primarily alveolar
macrophages
Diagnostic morphologic changes in BAL fluids
Smoker with
interstitial lung
disease
many
carbonaceous
macrophages
Diagnostic morphologic changes in BAL fluids
Sarcoidosis:
increased numbers
of lymphocytes: CD4
alveolitis
BAL from a Scleroderma Patient
Typical bronchoalveolar lavage from a patient with systemic sclerosis illustrating neutrophils and eosinophils
Classification of Idiopathic Interstitial Pneumonias
IPF = Idiopathic pulmonary fibrosis, NSIP = Non-specific interstitial pneumonia, COP =
Cryptogenic organizing pneumonia, AIP = Acute interstitial pneumonia, DIP =
Desquamative interstitial pneumonia, LIP = lymphoid interstitial pneumonia, RBILD =
Respiratory bronchiolitis-associated interstitial lung disease
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
•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
Events in the Development of IPF
Vasodilation
Coagulation
Oxidative stress
Vascular remodeling
Increased expression: TGF-β TNF-α PDGF Injury, failed repair, fibrosis with activated myofibroblasts and fibroblastic foci
Evidence for the Role of Cellular and Humoral Immunity in IPF
- Involvement of CD4+ T cells (activated phenotype)
- Biased T cell receptor Vβrepertories (BAL and peripheral)
- Presence of autoantibodies in some studies with IPF patients
- Evidence of lymphoid neogenesis without organized structure
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 *MUC5Bpromoter polymorphism and pulmonary fibrosis. N Engl J Med 2011; 364: 1503-12.
Connective Tissue Diseases
- Rheumatoid arthritis (RA)
- Systemic lupus erythematosus (SLE)
- Sjögren syndrome
- Systemic sclerosis (SSc)
- Pulmonary manifestations include ILD
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
Relevant proteins
TNF-α
IL-7
MMP-12
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
Immunology Associated with HP
- Prior sensitization is necessary
- Not associated with IgE or eosinophils
- Higher prevalence in non-smokers (80-95%)
- > 40% lymphocytes suggestive of HP; higher percentage of neutrophils and degranulated macrophages
- Cell-mediated immune process
- Tx with corticosteroids aids recovery initially, long-term outcome is unaffected
Immunology Associated with HP
•Cell-mediated immune process
–TGF-β, IL-1, IL-12, TNF-α
–IL-2, IFN-
–IL-6, IL-17, IL-22
airway epithelium
toll like receptors when activated they secrete cytokines and defensins
alveolar macros
eat
Lymphocyte-mediated immunity
Neutrophils and eosinophils
eosiniphilic lung disease when they get out of control
BALT and GALT
t and b cells are activated in lymph nodes
dendritic cells pick up antigen and go to lymph node and then t and b cells are activated
t and b cells traffic back to where they antigen was found
Inflammatory Response in Sarcoidosis
predominant th1 response the dendritic cell is presentin the antigen to the cd4 th1 cell on class 2 molecules the th1 cells have cytokines as ifn y and the dendritic ell relase il2 il18, tnf a il7 and mmp 12 and ifny
there is proliferation and activation of the tcells with tnf a and there is persistent inflammation in alveolar space with no resolution so you get alveolitis which leads to ild
IL-2, IFN-gamma
th1 cd4
IL-6, IL-17, IL-22
th17
th1
inflammation
th2
fibrotic
Eosinophilic Lung Diseases
predominance of eosinophils
Simple Pulmonary Eosinophilia
Etiology -
Duration of symptoms -
Respiratory Failure -
Blood Eosinophls -
BAL findings -
Dehst Radiographic -
Pleural Effusions -
Treament -
Clinical Relapse -
Etiology - idiopathic drugs parasites
Duration of symptoms - 1-2 weeks
Respiratory Failure - never
Blood Eosinophls - increased
BAL findings - eosinophils
Dehst Radiographic - transient opacities
Pleural Effusions - rare
Treament - unnecessary
Clinical Relapse - rare
Chronic Eosinophilic Pneumonia
Etiology -
Duration of symptoms -
Respiratory Failure -
Blood Eosinophls -
BAL findings -
Dehst Radiographic -
Pleural Effusions -
Treament -
Clinical Relapse -
Etiology - idiopathic
Duration of symptoms - several weeks to months
Respiratory Failure - very rare
Blood Eosinophls - increased
BAL findings - eosinophils
Dehst Radiographic - peripheral opacities
Pleural Effusions - rare
Treament - several years
Clinical Relapse - frequent
Acute Eosinophilic pneumonia
Etiology -
Duration of symptoms -
Respiratory Failure -
Blood Eosinophls -
BAL findings -
Dehst Radiographic -
Pleural Effusions -
Treament -
Clinical Relapse -
Etiology - idiopathic tobacco smoke drugs
Duration of symptoms - 1-5 days
Respiratory Failure - frequent
Blood Eosinophls - normal
BAL findings - eosinophils lymphocytes and neutrophils
Dehst Radiographic - diffuse opacities kerley b lines
Pleural Effusions - frequent
Treament - 2-12 weeks
Clinical Relapse - rare
