Hypersensitivity Flashcards
Examples of innate response in lung
Sputum
Cilia
Examples of adaptive response on lung
Pus
Swelling
Granuloma
Type 1 hypersensitivity mediators
IgE antibodies
Type 1 hypersensitivity timing
Immediate- within 1 hour
Type 1 hypersensitivity examples
Anaphylaxis
Hay fever
Atopy
Type II hypersensitivity mediators
Cytotoxic
Autoimmune- Antibodies bound to cell antigen
IgG/M binds self antigens on host cells
Type II hypersensitivity timings
Hours to days
Type II hypersensitivity examples
Transfusion reactions
Goodpastures (anti GBM disease)
HDFN
Mycoplasma pneumonia (RBC antigen)
Type III hypersensitivity mediators
Deposition of immune complexes
Type III hypersensitivity timing
Typically 7-21 days
Type III hypersensitivity examples
Hypersensitivity pneumonitis / allergic alveolitis eg farmers/ hot tub lung
Lupus
Post streptococcal glomerulonephritis
Rheumatoid arthritis
Type IV hypersensitivity mediators
T-cells
Type IV hypersensitivity timing
Days to weeks or months
Type IV hypersensitivity examples
Granulomatous disease: Tuberculosis, sarcoidosis and dermatitis
Stevens-Johnson syndrome
Type I
Antigen interacts with IgE bound to mast cells or basophils
Degranulation of mediators lead to local effects
Histamine the predominant mediator
Type I treatment
Steriods
Adrenaline (0.5 mg or auto injection in community intramuscularly)
Antihistamine
Tryptase measurements
Observation (second peak may occur circa 12 hours)
Anaphylaxis
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.
Type II
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
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
Diagnosis of GBM
requires high degree of clinical suspicion
GBM antibodies in serum or on biopsy (usually of kidney)
Treatment of GBM
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)
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
Type III
Antigen-immunoglobulin complexes are formed on exposure to the allergen
These are deposited in tissues and cause local activation of complement and neutrophil attraction
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
Treatment by removal of antigen +/- immunosuppression
Type IV
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
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
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
Consequences of T-cell hyperactivity
Diabetes
Thyroid disease
Hepatitis
Nephritis
Myositis
Any –itis!
Life threatening pneumonitis
-MUST STOP DRUG
-Steroids may be helpful
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
How many types of hypersensitivity are there
4
Type I hypersensitivity mechanism
Antigen exposure —> Th2 release IL-4 —>B cell release IgM —> become IgE—-> activates FcER1 on mast cells —> allergen causes IgE cross-linking —> degranulation- histamine release
Type III hypersensitivity mechanism
Antigen-IgG complexes precipitate- complement activation and neutrophil attraction
Can’t be cleared by macrophages
Type IV hypersensitivity mechanism
Th release cytokines and macrophages become giant cells—> granulomar around pathogens
Anaphylaxis
Biphasic response
Cytokines released activate granulocytes —> release of newly synthesised mediators from mast cells
Systemic effects of anaphylaxis
Bronchoconstriction
Hypotension (due to vasodilation)
Angioedema (swelling)
Urticaria (itchy rash)
Mechanism of type 1 hypersensitivity
Basophils and mast cells
Sensitising agents elicit IgE antibody response
IgE binds to mast cells and basophils causing degranulation and the release of chemical mediators histamine, prostaglandins and leukotrienes
Results in vasodilation and bronchospasm
Cough receptors (pulmonary irritant receptors) are protective of the lungs. Which of the following best describes the purpose of coughing?
move material from the vocal cords to the pharynx
