Hypersensitivity Flashcards
Give examples of extrinsic and intrinsic antigens which cause hypersensitivity.
Extrinsic antigens:
- non-infectious substances
- infectious microbes —> over-activation of immune response —> septic shock (esp. Gram-ve bacteria)
- drugs
Intrinsic antigens:
- infectious microbes —> mimic host cells so immune response damages microbes and host cells
- self-antigens
Give some examples of specific infections which drive hypersensitivity reactions against self-antigens.
Rheumatic heart disease affects:
- Strep. pyogenes AND
- antigen in cardiac muscle —> endocarditis
Guillain-Barré syndrome (usually self-limiting - 8-9months) affects:
- Campylobacter jejuni AND
- myelin-associated gangliosides
Type 1 diabetes affects:
- Coxsackieviruses AND
- pancreatic islet cells
What is the pathophysiology of autoimmune diseases caused by hypersensitivity to self-antigens? What are some associated risk factors?
Immune response (antibody and cell-mediated) against self-antigens/pathogens that lead to tissue damage or disturbed physiological function
Presence of autoantibodies is normal (only an autoimmune disease when they cause a pathological response)
Rare in childhood; peak years between puberty and retirement age
Hormonal factors - females affected more
Genetic factors (HLA)
Environmental factors e.g. exposure to smoke, solvents, etc.
What are the features of type I hypersensitivity reactions? Give some examples of conditions.
PATHOPHYSIOLOGY:
- immediate (less than 30min)
- caused by environmental non-infectious antigens
- affects individuals predisposed to hypersensitivity
- IgE mediated
- soluble antigens
- cause mast cell activation
CONDITIONS:
Systemic anaphylaxis:
- common allergens = drugs, serum, venoms, peanuts
- IV or PO route of entry
- causes oedema (increased vascular permeability) —> tracheal occlusion; circulatory collapse —> death
Acute urticaria:
- common allergens: animal hair, insect bites, skin prick tests
- route of entry is through skin
- causes a local increase in blood flow and vascular permeability ——> wheal and flare reaction
Allergic rhinitis (hayfever):
- common allergens: pollens, dust mite faeces
- route of entry is inhalation
- causes irritation and oedema of nasal mucosa
Asthma:
- common allergens: cat dander, pollens, dust mite faeces
- route of entry is inhalation
- causes bronchoconstriction, increased mucus production, and airway inflammation
Food allergy:
- common allergens: nuts, shellfish, milk, eggs, fish
- PO route of entry
- causes vomiting, diarrhoea, pruritis, urticaria, and anaphylaxis
What is the mechanism of the treatment for anaphylaxis?
IM adrenaline
Inhibits mast cell activation
Reverses peripheral vasodilatation —> alleviates hypotension
Reduces oedema
Reverses airway obstruction/bronchospasm
Increases force of contraction of the heart
note: reactivation may occur (multiple doses required)
What are some of the features of type II hypersensitivity reactions? Give some examples of conditions.
PATHOPHYSIOLOGY:
- 5-12hrs
- caused by response to infection or autoantigens
- IgG/IgM-mediated
- cell surface receptors and cell/matrix associated antigens
- antibody-dependent activation of complement —> opsonisation, chemotaxis, cell death
- antibody-dependent cell-mediated cytotoxicity
CONDITIONS:
Graves’ disease = autoantibody against TSH
Myasthenia gravis = autoantibody against AChR
Pernicious anaemia = autoantibody against intrinsic factor/gastric parietal cells
Goodpasture’s syndrome = anti-GBM autoantibodies and IgA deposition in collagen of alveolar and glomerular basement membranes
Transfusion reactions
Rhesus haemolytic anaemia
Autoimmune haemolytic anaemia
Idiopathic thrombocytopenic purpura
Define hypersensitivity. What are the different phases?
Antigen-specific immune responses that are either inappropriate or excessive and result in harm to the host
- Sensitisation phase = first encounter with antigen
- Effector phase = clinical pathology upon re-exposure to the same antigen
What is rhesus haemolytic anaemia? How is it treated?
Rh-ve mother carrying Rh+ve foetus becomes sensitised and produces Rh-ve antibodies after delivery
If carrying another Rh+ve foetus, the anti-Rh antibodies will cross the placenta and damage the foetal RBCs
Prevent by giving IgG anti-RhD during first pregnancy/within 72hrs of delivery —> prevents recognition of Rh+ve antibodies —> prevents development of anti-RhD antigens
What are the causes of autoimmune haemolytic anaemia? How is it diagnosed?
Causes:
- idiopathic
- infections e.g. EBV, Mycoplasma
- autoimmune disorders e.g. SLE
- lymphoproliferative disorders
Diagnosis:
- direct Coombs test = blood samples from patient (have antigens on surface of RBCs) —> incubate with anti-human antibodies (Coombs reagant) —> RBCs agglutinate (antibodies form cross-links)
- indirect Coombs test = add patient antibodies to donor blood sample —> form antibody-antigen complexes —> RBCs agglutinate (antibodies form cross-links)
What are the features of type III hypersensitivity reactions? Give some examples of conditions.
PATHOPHYSIOLOGY:
- 3-8hrs
- caused by response to infection or autoantigens
- IgG/IgM-mediated
- soluble antigens (exogenous or endogenous) form circulating immune complexes
- non organ-specific
- tissue damage due to deposition (difficult to opsonise) —> complement activation, platelet aggregation, chemotaxis
CONDITIONS:
Rheumatoid arthritis: anti-Rheumatoid factor IgG in 75%
Glomerulonephritis: caused by bacterial endocarditis, hepatitis B
SLE: have anti-nuclear antibodies (ANA; sensitive but non-specific) and anti-dsSNA antibodies (highly specific)
What are the features of rheumatoid arthritis? What are some poor prognostic factors?
Articular and extra-articular features
Episodes of inflammation/remission
Poor prognostic factors:
- younger than 30yrs
- high titre of rheumatoid factor
- female
- joint erosions
How is SLE diagnosed?
More common in women
~40%-60% have cardiac, resp., renal, joint, and neurological features
Often have repeated miscarriages
DIAGNOSIS:
- skin criteria e.g. malar/butterfly rash
- systemic criteria e.g. kidney, arthritis
- presence of anti-nuclear and anti-dsDNA antibodies
What are some of the features of type IV hypersensitivity reactions? Give some examples of conditions.
PATHOPHYSIOLOGY:
- 24-48hrs
- caused by environmental infectious agents and self-antigens
- cell-mediated =
Th1 = macrophage activation; involved in contact dermatitis, tuberculin reaction
Th2 = IgE production, eosinophil activation, mastocytosis; involved in chronic asthma and chronic allergic rhinitis
Natural killer cells = cell-associated antigens, cytotoxicity; associated with contact dermatitis
CONDITIONS:
Granulomatous e.g. TB, tuberculoid leprosy, schistosomiasis, sarcoidosis
Type 1 diabetes mellitus
Hashimoto’s thyroiditis (thyroid peroxidase)
Rheumatoid arthritis (IgG)
Coeliac disease (anti-reticulin antibodies and Howell-Jolly bodies)
What are some of the therapeutic options for treating type 4 hypersensitivity reactions?
Replacement of function
Immunosuppression
Monoclonal antibodies (including anti-TNF-alpha) e.g. infliximab, adalimumab
High dose IV Ig (prevents opsonisation —> prevents recognition by immune system)
Splenectomy
Plasmapheresis
What antibiotics need to be avoided in penicillin allergy?
- co-amoxiclav (Augmentin - amoxicillin + clavulanic acid )
- amoxicillin
- flucloxacillin
- temocillin
- ampicillin
- benzylpenicillin (penicillin G)
- co-fluampicil
- phenoxymethylpenicillin (penicillin V)
- piperacillin
- Tazocin (piperacillin + tazobactam)
- pivmecillinam
- ticarcillin
- Timentin (ticarcillin + tazobactam)
Avoid/use with caution:
- cephalosporins
- carbapenems
