Hypersensitivity And The Lung Flashcards
What does the immune system (cellular response) comprise of?
Phagocytes e.g. monocytes and neutrophils phagocytose (envelop the invader) and some present to other cells
Lymphocytes: make and release antibodies and kill diseased cells
What does the immune system (humoral response) comprise of?
Immunoglobulins
Complement (form membrane attack complex)
Cytokines (allow communication between leukocytes and tissue cells)
What are antibodies?
Produced by B-lymphocytes (plasma cells)
Neutralises or eliminates pathogens
May also cause disease…
What does IgM do?
IgM: Circulating tetramers made at the beginning of infection.
What does IgG do?
IgG: Monomer highly specific antibodies targeting single epitopes.
What does IgE do?
IgE: Likely to have developed in response to parasitic threats. Implicated in allergy, particularly alongside eosinophils
What does IgA do?
IgA: Expressed in mucosal tissue. Forms dimers. Protects the neonatal gut (expressed in breast milk)
What does IgD do?
IgD: Monomers, induction of antibodies in B cells, activates basophils and mast cells
What is the Gell and Coombs Classification?
Recognition of foreign antigen can cause collateral tissue damage
Conceptualised in the early 1960s
Imperfect classification, but still holds as description of pathology
Does not hold well for complex immune reactions
What happens in Type 1 hypersensitivity?
Antigen interacts with IgE bound to mast cells or basophils
Degranulation of mediators lead to local effects
Histamine the predominant mediator
What happens when someone has an anaphylaxis shock due to peanuts?
Sudden onset
Systemic degranulation of mast cells and histamine release
Skin, eyes, lips swelling, hypotension
Bronchospasm can result in airway occlusion and death if not quickly and accurately managed.
What is the management to anaphylaxis shock due to peanuts?
Adrenaline 0.5mg (1:1000) or auto injector in community intramuscularly
Steroids
Antihistamines
Observation (second peak may occur circa 12 hours)
Tryptase measurements
What happens in Type 2 hypersensitivity?
Antibodies reacting with antigenic determinants on the host cell membrane
Usually IgG or IgM
Outcome depends on whether complement is activated and if metabolism of cell is affected
What is Anti Glomerular Basement Membrane Disease?
Rare but deadly type II HS disease
Goodpasture syndrome = alveolar involvement
GBM is made of type IV collagen present in alveoli and kidneys (glomeruli)
Alpha 3 subunit becomes antigenic
What is the diagnosis for Anti Glomerular Basement Membrane Disease?
Diagnosis requires high degree of clinical suspicion
GBM antibodies in serum or on biopsy (usually of kidney)
What is the treatment for Anti Glomerular Basement Membrane Disease?
Treatment with plasmapheresis (removal of plasma from patient to extract offending Abs)
Immune suppression (cyclophosphamide, steroids, rituximab)
Supportive treatment of lungs (ventilation) and kidneys (haemodialysis / filtration)
What is Mycoplasma Pneumonia?
“Atypical” pneumonia
Cross reacting epitopes
Antibodies to M.Pneumonia also react to I antigen of red cells
Causes agglutination and haemolysis
Up to 50% of cases
What is Type 3 hypersensitivity?
Antigen-immunoglobulin complexes are formed on exposure to the allergen
These are deposited in tissues and cause local activation of complement and neutrophil attraction
What is Hypersensitivity pneumonitis?
Formerly “extrinsic allergic alveolitis” (EAA)
Immune complexes formed with a range of different antigens
Deposited in the acinar airways leading to inflammation acutely and scarring chronically
What is the treatment for Hypersensitivity pneumonitis?
Treatment by removal of antigen +/- immunosuppression
What is Type 4 hypersensitivity?
T-cell mediated, releasing IL2, IFᵧ and other cytokines
Requires primary sensitisation
Secondary reaction takes 2-3 days to develop
May result from normal immune reaction – if macrophages cannot destroy pathogen, they become giant cells and form granuloma
What is the Mantoux / Tuberculin skin test?
Subcutaneous injection of tuberculosis protein
Interpreted at 48-72 hours
Diameter of induration determines positivity
Positive only if exposed to TB of vaccine previously
What is Sarcoidosis?
Possibly reaction to mycobacteria
Multisystem disease causing granuloma
Eyes, skin, lungs, heart, nervous system…
80% regress spontaneously
Some require systemic treatment – steroids, methotrexate, others
What are consequences of T-cell hypersensitivity?
Diabetes
Thyroid disease
Hepatitis
Nephritis
Myositis
Any –itis!
Life threatening pneumonitis
MUST STOP DRUG
Steroids may be helpful
