immunologic lung diseases Flashcards
th2 cytokines
il-4,5,10,13
th1 cytokines
il-2, ifn-y
th1 role
killing microbes, autoimmunity, activate macrophages
th2 role
antibodies, extracellular parasites, allergy
th17 role
induction of inflammatory response, autoimmunity
treg role
dampening immune activation, tolerance
innate immunity immunologic lung diseases
pneumonia, ards
granulomatous immunologic lung disease
tb
sarcoid
egpa (esosinophilic granulomatosis with polyangitis)
autoimmune and vasculitis lung disease
gpa (granulomatosis with polyangitis)
sle
rheumatoid lung
anti-gbm disease
th-1 related lung diseases
hypersensitivity pneumonitis, copd
th-2 related lung diseases
allergic asthma, abpa (allergic bronchopulmonary aspergillosis)
extrinsic allergic alevolitis= ?
hypersensitivity pneumonitis
signs of hypersensitive pneumonitis?
cough, dyspnea, fever
most common causes of HP?
thermophilic actinomycetes, fungi, bird proteins
how do you diagnose hp?
ouchterlony test for igG directed against allergen
pathology of hp?
in a genetically susceptible host, antigen exposure activates the immune system, causing alveolitis, granulomatous inflammation, and fibrosis
cells involved in hp?
b cell (igG antibodies) and t cell mediated (th1, IFN-gamma)
clinical features of acute HP?
4-48 hrs: fever, chills, cough, hypoxemia, aches, tachypnea, fine rales
clinical features of subacute HP?
weeks-4 mo: dyspnea, cough, episodic flares, tachypnea, diffuse rales
clinical features of chronic HP?
4 mo-years: dyspnea, cough, fatigue, weight loss, +/- clubbing
hrct on acute hp?
ground glass infilatrates
hrct in subacute hp?
micronodules, air-trapping
hrct in chronic hp?
fibrosis, honeycombing, emphysema
prognosis in HP?
good for acute and subacute, chronic is poor
immunopathology of acute hp?
macrophage, lymphocyte response (th1) to antigen, immune complexes
immunopathology of subacute hp?
formation of GRANULOMAS and lymphoid follicles containing plasma cells, activated b cells
immunopathology of chronic hp?
lymphocytic infiltration, collagen formation, FIBROSIS, neutrophil-mediated air space destruction
bronchoalveolar lavage in HP?
inc. total cell count, increased T lymphocytes (more CD8/CD4)
diagnostic criteria for hypersensitivity penumonitis
- exposure to known antigen
- precipitating antibodies to antigen
- recurrent episodes
- inspiratory crackles on PE
- symptoms occur 4-8 hours after exposure
- weight loss
spirometry of HP?
restrictive patterns and reduced diffusion
management of hp?
trial of corticosteroids in acute phase; longer course at higher doses often necessary for subacute phase–efficacy not established
immunology of abpa?
th2 and eosinophils
what is allergic bronchopulmonary aspergillosis?
allergic inflammatory response to colonization by aspergillus and other fungi; characterized by asthma, pulmonary infiltrates, mucus plugging, proximal bronchiectasis
what is aspergillus?
ubiquitous fungus that grows in organic debris; hyphae branch at 45 degree angles, macrophages ingest and kill spores
normal response to aspergillus
macrophages ingest and kill spores, neutrophils bind to hyphae and damage cell walls with an oxidative burst
what happens in abpa?
virulence factors/mycotoxins cause th2 mediated inflammation
generation of eosinophil-rich mucoid impaction
activation of cd20 b cells which generate igE antibodies
criteria for diagnosis of abpa?
- asthma
- central bronchiectasis (inner 2/3 of chest CT)
- immediate cutaneous reactivity to aspergillus species
- total igE > 417
- elevated igE and or igG to A. fumigatus
non essential but supportive: infiltrtes on Cxr/ct; serum precipitating antibodies to Af, eosinophilia
lobe predominance in abpa?
upper lobe
spirometry in abpa?
obstructive; bd response in fewer than 1/2, air trapping, deification is reduced in minority (bronchiectasis)
drugs for abpa?
itraconazole (anti-fungal)
omalizumba (anti-igE–> use in CF patients where you can’t use steroids)
GPA stands for?
granulomatosis with polyangitis
what is vasculitis?
leukocytes in vessel wall with reactive damage to rural structures; loss of wall integrity leads to bleeding; compromise of lumen leads to ischemia and necrosis
gpa is an example of what kind of vasculitis?
small vessel that most commonly affects the upper airways, lower airways, and kidneys
upper airway disease in GPA:
sinus disease, epistaxis, septal perforation, subglottic stenosis
how do you diagnose gpa?
at least 2 of the following:
1) nasal or oral inflammation (painful or painless oral ulcers or purulent or bloody nasal discharge)
2) abnormal chest CT showing nodules, fixed infiltrates, or cavities
3) abnormal urinary sediment (microscopic hematuria with or without rbc casts)
4) granulomatous inflammation on biopsy of an artery or perivascular area
AND positive c-anca
what else is anca associated vasculitis?
gpa, mpa (microscopic polyangiitis), egpa (eosinophilic…), renal limited vasculatis
egpa is ____=anca?
perinuclear (p-anca)–> antibodies to strong cations (myeloperoxidase)
what is c-anca?
antibodies to neutral proteins or weak cations (proteinase 3)
immunopathogenesis of gpa?
activated Cd4 T cells; B cells, neutrophils
spirometry in gpa?
restrictive with reduced diffusion
