Hypersensitivity Flashcards
What is an allergy?
IgE mediated antibody response to external antigen (allergen)
What are the clinical features of Type 1 allergic disease?
- quick after exposure to antigen (minutes-hours)
- site of contact related to
site of presentation - More than one organ system
- threshold influenced by other things (alcohol, excersise, infection)
Which vasoactive substance to mast cells synthesize on demand?
Leukotrienes
Prostaglandin
Cytokines: TNF & IL4
Why is there no allergic reaction the first time host exposed to allergen/antigen?
Because the allergen-specific IgE antibody is synthesized by B cells the first time.
Allergen is cleared before IgE binds to mast cells..
What is the role of mast cells in allergic reaction?
Body has previously been exposed to allergen and B cells have synthesize allergen-specific IgE antibodies…
Antigen binding to IgE COATED MAST CELLS stimulates:
Release of preformed vasoactive mediators
Increased transcription of leukotrienes and cytokines (IL4 & TNFa)
How does IgE bind to mast cells?
Via Fc receptors (bottom of Y bit)
What are the two types of asthma?
Intrinsic: “non-allergic” non IgE mediated
Extrinsic: IgE mediated, external allergen
Pathophysiology of asthma?
Mast cell degranulation results in
- Muscle spasm: broncoconstriction: wheeze
- Mucosal inflammation: mucosal oedema: sputum production
- Inflammatory cell (eosinophils & lymphocytes) infiltrates bronchioles: yellow sputum
What are some manifestations of allergic reactions?
Urticaria (wheals)
Angioedema (swelling of subcutaneous tissue)
Diarrhoea, vomiting
Anaphylaxis
What is anaphylaxis?
characterized by low blood pressure - type of hypovolemic shock
SOB, itchy rash, swollen tongue
What else (other than IgE) causes spontaneous mast cell degranulation?
Drugs (morphine, aspirin) - can induce asthma
Thyroid disease
Physical urticaria due to pressure or heat
How can you test for allergic disease?
- Skin prick
- Measure amount of IgE primed against allergen
- Supervised exposure to antigen
TRUE/FALSE
Skin testing is the “gold standard” to support a diagnosis of allergy
TRUE
What is skin prick test?
Expose patient to standardised solution of allergen extract through a skin prick to the forearm
Positive reaction = Local wheal and flare response
TRUE/FALSE
Corticosteroids do influence skin prick tests
FALSE
they do not
TRUE/FALSE
Antihistamines do not influence skin prick tests
FALSE
they do, should be discontinued 48hrs before testing
What are the pros of skin prick testing?
Cheap
Quick (15 minutes)
Unrivalled sensitivity for the majority of allergens, particularly aeroallergens
Patient can see the result
What are the cons of skin prick testing?
Requires experience for interpretation
Very rarely may induce anaphylaxis (1:3000)
TRUE/FALSE
Measuring total IgE is useful for diagnosing/investigating allergic disease
FALSE
There are many causes of raising total IgE e.g. vasculitis, drugs etc.
When should specific IgE tests be used (RAST)?
Skin test not available
75% specificity /sensitivity comp skin prick
What is the investigation used during acute anaphylactic episode?
Serum tryptase levels (tryptase product mast cell granules)
TRUE/FALSE
Rise in tryptase level only occurs in anaphylaxis, and not in local reactions
TRUE
Treatment anaphylaxis?
Adrenalin constrict arterial smooth muscle
dilates bronchial smooth muscle
Management IgE allergic disorders?
Trigger (history!) avoid allergen Block mast cell activation prevent effects mast cell activation Anti-inflammatory agents Manage anaphylaxis Immunottherapy
What is sodium cromoglycate?
Mast cell stabilizer, blocks mast cell activation
What are some drugs that block effects of mast cell activation?
Histamine receptor antagonist
Leukotriene receptor antagonist
TRUE/FALSE
Histamine receptor antagonists are used prophylactically and to control symptoms
TRUE
Step up treatment maximall y=
corticosteroids
Immunotherapy allergic disease?
Controlled exposure to increasing amounts of allergen
Subcutaneous injection of tiny amounts of allergen
Followed by gradual increase in dose
RISK IS ANAPHYLAXIS
Pathophysiology of Type II Hypersensitivity?
Antibody binds to CELL SURFACE antigen
IgG and IgM :Activation complement via classical pathway (cell lysis and release opsonins)
IgG: Summon NK cells
What do fragments of C3a and C5a do after activation of complement system?
Increase permeability of blood vessels - anaphylotoxins
What are the effects of antibody binding to cell membrane protein?
- complement activation and osmotic lysis of cell via Massive Attack Complex
- NK and eosinophil activation
- Antibody acts as opsonin - complement acts as opsonin2
- Phagocytosis of antigen +ve cells
What are transfusion reactions?
Antibodies binds to cells of transfused RBCs. Complement mediated lysis -pyrexia/rigors -tachycardia/pnoea -hypotension FATAL
TRUE FALSE
Immediate Haemolytic Transfusion Reaction begins after at least 50mls of blood is transfused
FALSE!
May begin after only 1 ml blood is transfused
Overwhelming systemic inflammatory response
What is Grave’s disease?
Antibodies bind to thyroid stimulating hormone RECEPTOR -> HYPERthyroidism
Popping eyes
TRUE/FALSE
Many type II hypersensitivity diseases are associated with Autoimmune disease
TRUE
TRUE/FALSE
Only mothers with mild or overt symptoms of autoimmune disease may pass on autoantibodies to neonatt
FALSE
mothers may have no symptoms
How can Type II Hypersensitivity be managed?
Plasmapheresis
Immunosuppression to switch off B cell production
What is plasmapheresis?
removal of pathogenic antibody, remove patient plasma and replace with someone else’s
Major disadvantage of plasmapheresis?
Rebound antibody production
What is the pathophysiology of Type 3 hypersensitivity reactions?
Antibody SOLUBLE in antigens due to EXCESS antigens
Forms small immune complexes which trapped in small blood vessels/joints/glomeruli
This activates complement and attracts neutrophils
- damage endothelial cells and basement membranes
TRUE/FALSE
Cheese worker’s lung due to mouldy cheese is a genuine Type III hypersensitivity
TRUE
Malt - mouldy maltings
Farmer’s lung - mouldy hay
Bird Fancier’s lung - avian excreta, feathers
Lung - accumulation and inflammation WITHIN alveoli
TRUE/FALSE
Acute hypersensitivity pneumonitis and chronic hypersensitivity pneumonitis have the same pathophysiology
FALSE
Acute is a Type III hypersensitivity
Chronic causes fibrosis
What are the features of acute hypersensitivity pneumonitis
Symptoms 4-8hrs after exposure Wheezing - inflammation terminal bronchi Malaise, pyrexia - systemic inflammation Dry cough, breathlessness - alveolitis, decreased efficiency of gas transfer Examination often normal
What is SLE
Systemic lupus erythematosus
T 3 hypersesntiivity
Antibodies against contents of cell nuclei
TRUE/FALSE
Immune complex deposition results in systemic small vessel vasculitis
TRUE Fever renal impairment vasculitic skin rash arthralgias
How to diagnose T 3 Hypersensitivity?
Test for presence of specific IgG antibodies that are reactive to putative antigen
For example: Anti-DNA binding antibodies (SLE), Antibodies to Aspergillus (Farmer’s lung)
How to manage T 3 Hypersensitivity?
(Avoidance) Decrease inflammation Corticosteroids Decrease production of antibody Immunosuppression
Type 4 hypersensitivity?
T CELL MEDIATED
Intial sensitization -> “primed” T effector cells
“DELAYED” hypersensitivity
How long does T cell sensitization take?
7-10 days
TRUE/FALSE
T cell sensitization results in dermatitis
FALSE
What are the consequences of TH1 cell activation?
- Chemotaxi = Macrophage recruitment site of antigen
- IFNy secretion = activates macrophages, releases TNFa
- TNFa secretion = Local tissue destruction
- Release GM- CSF(granulocyte-macrophage colony stimulating factor) stimulates maturation of neutrophils in bone marrow
Sarcoidosis is characterized by?
TYPE FOUR! T CELL MEDIATED = severe unknown antigen PERSISTANT STIMULATION Leads to TISSUE DAMAGE and FIBROSIS Leads to GRANULOMA formation
What is a granuloma?
organised collection of activated macrophages and lymphocytes
Management of sarcoidosis?
Watchful waiting many patients undergo spontaneous remission NSAIDS For acute onset of disease Systemic corticosteroids Block T cell activation Block macrophage activation
