Immunology - Hypersensitivity Reactions Flashcards
What are hypersensitivity reactions?
Immune response that results in bystander damage to self, usually an exaggeration of normal immune response
What are the four types of hypersensitivity reactions?
Type I - immediate hypersensitivity
Type II - direct cell killing
Type III - immune complex mediated
Type IV - delayed type hypersensitivity
Define allergy
IgE-mediated antibody response to external allergen
(Type I hypersensitivity)
How quickly do type I hypersensitivity reactions occur?
minutes to 1-2 hours
What may affect the threshold for allergic reaction?
cofactors such as exercise, alcohol and infection
What are specific features of allergic disease?
asthma
urticaria
angioedema
allergic rhinitis
allergic conjunctivitis
diarrhoea and vomiting
anaphylaxis
Which cells are involved in allergy?
B lymphoctes - recognise antigen, produce IgE
T lymphocytes - helper for B cells
Mast cells - release vasoactive substances
Which substances are preformed in mast cells?
histamine
tryptase
heparin
Which substances do mast cells synthesize on demand?
leukotrienes
prostaglandins
cytokines (including IL4, TNF)
What is the function of mast cells?
defense against parasites
wound healing
What role do mast cells play in the inflammatory cascade?
increase blood flow
increase vascular permeability
contraction of smooth muscle
increase secretions at mucosal surface
How long do hives normally last?
appear within 1 hour
last 2-6 hours, occasionally 24 hours.
What is angioedema?
Self-limited, localised swelling of subcutaneous tissues or mucous membranes
non-pitting oedema
often without clear demarkation
generally not itchy
What are the clinical features of anaphylaxis?
Angioedema of lips and mucous membranes
Laryngeal obstruction, stridor
Hypotension
Wheeze
Itch of palms, soles of feet, genitalia
Flushing
Urticaria
Oral itching
Vomiting, diarrhoea, abdominal pain
Loss of consciousness
Death
What are non allergic causes of mast cell degranulation?
Drugs: morphine & other opiates; aspirin and NSAIDS
Thyroid disease
Idiopathic
Physical urticaria - pressure & heat
What is Samter’s triad?
Asthma
Nasal Polyps
Severe end of aspirin sensitivity spectrum
What are the general features of allergic reaction?
Reaction occurs quickly
Responses are often consistent
Often associated with more than one organ system
What are the investigations for allergy?
Skin prick tests
Quantitive IgE to putative allergen
Challenge test
What investigation would you perform during an acute anaphylactic episode?
Serum mast cell typtase levels - evidence of mast cell degranulation
What drugs need to be stopped for skin prick tests?
Antihistamines for 48 hours
How does the sensitivity and specificity of IgE RAST test compare with that of skin prick testing?
70-70%
What are common causes of elevated total IgE?
Allergic disorders
Vasculitis
Lymphoma
Drugs
What are the pitfalls of measuring total IgE in allergy?
Many other causes of elevated IgE
Significant allergic disease can exist in absence of elevated IgE
When does tryptase reach its peak concentration during anaphylaxis? When does it return to baseline?
Peak 1-2 hours
Baseline 6 hours
How do adrenalin injection pens work in anaphylaxis?
β2-adrenoreceptors
Constrict arterial smooth muscle - increases blood pressure, reduces vascular leakage
Dilates bronchial smooth muscle
What is immunotherapy?
Controlled exposure to increasing amounts of allergen
What are the risks of immunotherapy?
Anaphylaxis
What are the key features of Type II hypersensitivity reactions?
Antibody to cell surface antigens
resulting in
activation of complement
antibody mediated phagocytosis
What type of hypersensitivity reactions are transfusion reactions?
Type II
Anti-blood group antibodies bind to surface of circulating donor erythrocytes
What are the features of immediate haemolytic transfusion reaction?
Overwhelming systemic response occuring after only 1ml blood transfused
Pyrexia and rigors
tachycardia/tachypnoea
hypotension/dizziness
headaches, chest or lumbar pain
May be fatal
Give some examples of Type II hypersensitivity.
Transfusion reactions
Autoimmune haemolytic anaemia
Idiopathic thrombocytopaenic purpura
Goodpasture’s syndrome (kidney)
Myasthenia gravis (nervous system)
Guillan Barre (nervous system)
Grave’s disease (TSH receptor - hyperthyroidism)
Pemphigus vulgaris (skin)
What is the management for type II hypersensitivity?
Plasmapheresis
(limited by rebound antibody production)
Immunosuppression
(switch of B cell production of antibody)
What causes Type III hypersensitvity reactions?
Deposition of antigen-antibody immune complexes in small vessels causing complement activation and infiltration of macrophages and neutrophils
What are the clinical features of acute hypersensitivity pneumonitis (type III)?
wheezing and malaise, 4-8 hours after exposure
Dry cough, pyrexia, breathlessness
Examination often normal
Cell accumulation and inflammation within alveoli
What type of hypersensitivity reaction is Systemic Lupus Erythematous?
Systemic Type III
Antibodies produced against contents of cell nuclei
Immune complexes deposited in small vessels in skin, joints, kidneys
Complement activation, recruitement of immune cells.
How are Type III hypersensitivity reactions diagnosed?
Specific IgG to putative antigen
Complement
How are Type III hypersensitivity reactions managed?
Avoidance
Corticosteroids to reduce inflammation
Immunosuppression to decrease antibody production
What are the anti-inflammatory effects of corticosteroids?
Inhibits Phospholipase A2 - blocks formation of inflammatory mediators:
Prostaglandin formation
Platelet Activating Factor
Arachidonic Acid
What is the effect of corticosteroids on phagocytes?
Decreased expression of adhesion molecules on endothelium - transient increase in neutrophil counts because they don’t leave the bloodstream for the tissues
Decreased release of proteolytic enzymes
What are the effects of corticosteroids on the number of circulating lymphocytes?
Decreased numbers of lymphocytes because:
lymphocytes are sequestered in lymphoid tissue and spleen
high dose is cytotoxic to lymphocytes
How is the function of lymphocytes blocked by corticosteroids?
Inhibition of cytokine expression
Inhibiting of antigen-induced T cell proliferation
Decreased antibody production by plasma cells
What are the metabolic side effects of corticosteroids?
diabetes
central obesity
protein catabolism (muscle wasting)
lipid abnormalities
adrenal suppression
What are the non-metabolic effects of corticosteroids?
Cataracts
Glaucoma
Peptic ulceration
Pancreatitis
Osteoporosis
Hirsutism
Acne
Moon face
How is Type IV hypersensitivity mediated?
T cells
Primed T cells are produced by initial sensitization to antigen
Subsequent exposure activates previously primed T cells causing
recruitment of macrophages, lymphocytes, neutrophils
Inflammatory cascade
Granuloma
Give examples of autoimmune Type IV hypersensitivity reactions.
Type I diabetes
Psoriasis
Rheumatoid Arthritis
Give examples of non-autoimmune Type IV hypersensitivity.
Nickel hypersensitivity
Tuberculosis
Leprosy
Sarcoidosis
Cellular rejection of solid organ transplant
What is characteristic of sarcoidosis?
Granuloma formation
Multi system disease
How is sarcoidosis managed?
Watchful waiting - many patient have spontaneous remission
NSAIDS (acute onset)
Systemic corticosteroids
Which occupational diseases are characterised by Type IV hypersensitivity and granuloma formation?
Beryllosis
Silicosis
Other dust diseases
What type of hypersensitivity reaction is the chronic stage of hypersensitivity pneumonitis?
Type IV
