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what are the physical, chemical, humoral and cellular defences of the innate immunity of respiratory tract?
- phsical: nasal turbinates, hair, mucociliary escalator
- chemical: defensins, surfactant
- humoral: complement
- cellular: neutrophila, macrophage, eosinophils, mast cells
which Ab is predominantly secreted in the PROXIMAL airway?
which T cell subset is predominant in the PROXIMAL airway?
which Ab is predominantly secreted in the DISTAL airway?
give an example of a PRIMARY immunodeficiency
give an example of a SECONDARY immunodeficiency
related to underlying disease e.g. HIV or postBM transplant
what is the commonest innate immunodeficiency of the lung? and how does it cause immunodeficiency?
cigarette smoking: paralyses mucociliary escalator
why do ex-smokers initially suffer increased cough?
no mucociliary escalator
what is primary ciliary dyskinesia? what are consequences? (2)
- rare genetic condition affecting ciliary function
- leading to reps infection and INFERTILITY
how do patients with Ab deficiency present?
infection of sino-pulmonary tract (strep pneum, h.infl)
is 2ry Ab deficiency common or rare?
what can cause secondary Ab defiency?
- IgG loss: kidneys (nephrotic syndrome), gut (protein losing gut enteropathy, skin (massive burns)
- IgG impaired production: systemic illness malabsorption, sepsis
- IgG suppression of production: BM failure e.g. in leukaemia
give an example of primary Ab deficiency?
what is the commonest severe antibody deficiency in adults?
common variable immunodeficiency
in adults what is the commonest cause of cellular immunodeficiency?
secondary to HIV get low CD4 levels - permit opportunistic infection with fungi PCP or CMV
what is type1 hypersensitivity reaction and give an e.g.?
IgE mediated, allergic diseases, atopy..
what is type2 hypersensitivity reaction and give an e.g.?
direct antibody mediated eg Goodpasture's syndrome, M.Gravis (antiAChR Ab)
what is type3 hypersensitivity reaction and give an e.g.?
immune complex mediated e.g. hypersensitivity pneumonitis, EAA - get an Ab against an inhaled substance, SLE
what is type4 hypersensitivity? e.g.?
- cell mediated, delayed type
- sarcoidosis, TB, asbestos
what are the 2 Inx for allergy?
- 1. skin prick test: allergen introduced and reaction (wheal and flare) inspected after 15 mins. NB if already taking anti-histamines this test wouldn't work
- 2. Antigen specific IgE test by ELISA (still called RAST radioallergosorbant)
what is the action of the Th2 cytokine IL-5?
which Th2 cytokines provoke mucus hypersecretion and SM contraction and more Ab prod?
what component of BM are Goodpastures Ab directed to?
give 2 symptoms of Goodpastures
- renal failure
- pulmonary haemorrhage - smokers
what is farmer's lung?
- hypersensitivity pneumonitis. type 3 hypersensitivity (immune complex)
- inhale Ag e.g. mouldy hay - develop IgG Ab
- on re-exposure the formation of Ag-Ab complexes leads to acute pneumonitis:
- cough, fever, SOB
- illness subsides over DAYS if antigen is removed
what is the lab test for farmer's lung
measure precipitating antibodies against antigens e.g. mould
give 2 examples of small vessel vasculitis
- Churg Strauss disease
- Wegener's granulomatosis
give 2 examples of medium vessel vasculitis
Kawasaki, polyarteritis nodosa
give 2 examples of large vessel vasculitis
giant cell arteritis (aka temporal arteritis), Takayasu's arteritis
what are the general Ix done in systemic vasculitis?
- urinalysis - protein/blood
- urea & creatinine - renal failure
- CRP/ESR - monitor response to Rx
- Blood cultures - exclude endocarditis
- cryoglobulings - Ig precipitated by cold - deposit in fingers - vasculitis
- Transfer factor - increased in pulmonary haemorrhage (NB decreased in COPD)
- autoimmune serology: antiBM, pANCA
- lung and renal imaging
what situation may transfer factor be increased in?
what does pANCA mean? and which antibodies and diseases is it assoc. with?
- peripheral antineutrophil cytoplasmic antibody
- antibodies: MPO (myeloperoxidase)
- disease: microscopic polyangiitis, Churg Strauss syndrome, PSC
what does cANCA mean? which antibodies and disease is it assoc. with?
- cytoplasmic antineutrophil cytomasmic antibodies
- antibodies: PR3 (proteinase 3)
- disease: Wegener's granulomatosis (90% sensitivity)
if ANA is positive, what will the lab go on to test?
- dsDNA: lupus
- AB against ENA (extractable nuclear antigens) e.g. Ro=lupus/Sjorens; La=lupus; Sm=lupus, RNP=mixed CT diseaes; Scl70=systemic sclerosis; Jo1=polymyositis
what is Churg Strauss also known as? and what is it linked to? which Ab?
- eosinophilic vasculitis
- linked to atopy and asthma
- pANCA/MPO positive
where do you get symptoms in Churg Strauss?
- lower and upper resp tract
- peripheral neuropathy: inflam of epineural vessels - leading to mononeuritis multiplex
- skin: rash
what is the difference between cause and symptoms Goodpastures and Wegeners granulomatosis?
- Goodpastures syndrome: type2 hypersensitivity, direct Ab mediated, Ab against type4collagen of BM of lung and glomerular. get renal failure and pulmonary haemorrhage due to capillarities
- Wegeners granulomatosis: necrotising small vessel vasculitis. affects upper and lower resp tract, skin and kidneys.
- nasal inflam - collapsed nasal bridge
- sinus involvement - perforate palate or orbital plate
- lung - cavitiating lesions on CXR so confuse with TB and lung cancer
- 90% cANCA/PR3+
what is the difference between empyema and abscess?
- empyema: collection of pus in a PRE-EXISTING anatomical cavity eg pleural cavity
- abscess: collection of pus in a NEWLY FORMED cavity
give 3 examples of inorganic pneumoconiosis?
- coal dust: anthracosis
- silica: silicosis
what can inorganic pneumoconiosis present as?
- often clinically insig
- or direct interstitial fibrosis and bad resp compromise
what is pathology of inorganic pneumoconiosis?
inflam in interstitial, pleural effusions and fibrotic nodules
what is the syndrome when inorganic pneumoconiosis are assoc. with RA?
name 2 types of organic pneumoconiosis and their causative agent and general pathology?
- farmers' lung: actinomycetes in mouldy hay (fungal derived bacteria)
- bird fanciers' lung: animal proteins from faeces (birds)
- aka EAA/hypersensitivity pneumonitis
- sensitisation to organic inhaled allergen
what is the initial and later type of hypersens in organic pneumoconiosis?
- initial: type 3 immune complexes
- later: type 4 cell mediated response with granulomatous inflame
what 2 values are raised in sarcoidosis?
what is different to the granulomatous inflam in sarcoidosis compared to e.g. TB/wegeners?
- no necrosis in sarcoid
- just very round giant cells with epithelia cells around them
what is honeycomb lung? and what is it a feature of?
- idiopathic pulmonary fibrosis
- it is interstitial fibrosis leading to cystic air spaces
name 3 complications of interstitial lung diseases:
- resp failure type 1 (as restrictive)
- pulm hypertension
- cor pulmonale
which cells in the alveoli make surfactant?
type 2 pneumocytes
what are the complications of COPD?
- pneumonia (as inc mucus)
- pulm htn
- cor pulmonale
- respiratory failure type 2 (as obstructive)
- polycythaemia due to hypoxia
- pneumothorax: if the cystic spaces in the lung rupture then air into pleural space
how does the TLC differ in COPD from interstitial lung disease?
- COPD: TLC increased due to inc RV as there is inc airway resistance from obstruction
- interstitial lung disease: TLC decreased due to decreased lung COMPLIANCE
- NB diffusion capacity is reduced in both
what is the definition of chronic bronchitis? (6marks)
- clinical definition
- chronic sputum
- chronic cough
- on most days for 3 months a year
- for 2 consecutive years
- when not due to a specific disease e.g. TB
what is the definition of emphysema? 5 marks
- pathological definition
- abnormal permanent increase in the size of air spaces
- beyond terminal bronchiole
- with destruction of their walls
- but WITHOUT fibrosis
what is emphysema an imbalance of?
protease and antiprotease
what is the most common protease inhib?
alpha 1 antitrypsin
what 2 things do neutrophils release?
- oxygen free radicals
what 2 things inhibit alpha 1 antitrypsin?
- oxygen free rads (made by neutrophils)
- oxidants from cigarette smoke
what is the 2 main classification of emphysema, association, where located?
- Centriacinar: cigarette smoke, upper zones, increased protease 2ry to airway inflame
- Panacinar: alpha 1 antitrypsin deficiency, lower zones, decreased anti protease activity
what is the inheritance of alpha 1 antitrypsin and clinical sign?
- auto RECESSIVE
- Pi = protease inhibitor
- PiZZ (homozygous): emphysema before 40yo
- heterozygous: emphysema IF SMOKE
what is the most common type of asthma?
what is the difference between atopic and non-atopic asthma? (mechanism, triggers, age, sex, FH, tests)
- atopic (extrinsic): type1 hypersen, triggers are dust, pollen, animal dander, food, childhood, m>f, FH of atopy, skin prick test +ve wheal and flare to identify allergen
- non atopic (intrinsic): hyperactivity of airways, triggers: cold, stress, exercise, aspirin, viral, f>m, adult onset, no FH, skin prick test -ve
which drug can cause drug induced asthma?
what are the features of drug induced asthma?
nasal polyps, urticaria
how many phases contribute to the pathogenesis of asthma - airway obstruction?
- acute response(immediate): smooth muscle spasm, mucosal oedema
- late phase(12-24hrs): epithelial damage, inflame, mucus exudation
- chronic phase(with repitition): mucus gland hyperplasia, SM hypertrophy, bronchial BM thickening