Hypersensitivity Flashcards
What is hypersensitivity?
state of altered reactivity in which the body reacts with an exaggerated immune response to a foreign agent
What type is allergy?
hypersensitivity reaction (type 1)
What is an allergen?
antigen that causes an allergic reaction
What is type 1 hypersensitivity and what are examples?
IgE mediated via mast cells and basophils
atopy, anaphylaxis
What is type 2 hypersensitivity and what are examples?
cytotoxic responses via NK cells, complement and CD8+ T cell
haemolytic anaemia
What is type 3 hypersensitivity and what are examples?
immune responses complex via complement and neutrophils
serum sickness
What is type 4 hypersensitivity and what are examples?
cell mediated responses via T cells and macrophages
sarcoidosis
tuberculous (TB)
crohns
If there is a genetic predisposition for allergy what is this called?
atopy
What can the allergic reaction lead to?
anaphylaxis
What can allergens be?
proteins and haptens
What are haptens?
any small molecule that can be recognised by a specific antibody but cannot elicit an immune response
To elicit an immune response, what must a hapten do?
must be chemically linked to a protein molecule (carrier) to elicit antibody or/and T cell responses
When are IgE producing B cells activated?
during first exposure (sensitisation)
Where does IgE bind?
to Fc receptor on mast cells or CD63 on basophils
What does second exposure in IgE cause?
binds rapidly and causes immediate degranulation
What T cell causes proliferation of IgE?
TH2
What are the main roles of histamine?
- Immune cell recruitment
- Neurotransmitter
- Vasodilator
- Endothelial constriction
- Bronchoconstrictor
- Increase vessel permeability
What are examples of cutaneous atopy (localised) type 1 hypersensitivity?
– allergic rhinitis (hay fever)
– atopic dermatitis (allergic eczema)
– asthma (lower respiratory tract)
What is systemic anaphylaxis (systemic)?
– Anaphylactic shock throughout body
– Arises from mast cell degranulation
– Anaphylatoxins also produced by complement cascade (can be type II/III)
What are tests that can be done to identify an allergy?
skin prick/patch test (for skin allergies)
blood test for IgE levels
food challenges
What are drugs used for allergy and how do they work?
– Anti-histamines – compete with histamine for receptors
– Hydrocortisone – block histamine synthesis
– Cromoglycate – stabilises mast cells stops histamine release
– Epinephrine – best immediate treatment for anaphylactic shock reverses effects of granules (vasoconstriction, relaxes muscles)
What are immunological treatments?
– Hypo- or de- sensitisation
– repeat injections of allergen – IgE to IgG production
How do anti histamines work?
– compete with histamine for receptors (found on multiple cell types)
* Histamine receptors have basal activity
* Can be inverse agonists or antagonists
How does epinephrine work?
- increases peripheral vascular resistance
- improves blood pressure
- reverses peripheral vasodilation
- causes bronchodilation
- reduces inflammatory mediator release
How is complement activated in type 2 hypersensitivity?
by IgG or IgM binding to an antigenic cell (cell surface auto-antigens or haptens/allergens
What are cells lysed by in type 2 hypersensitivity?
– Membrane attack complex formation (complement)
– Antibody dependent cell mediated cytotoxicity (natural killer cells or CD8+ T cells)
What are examples of type 2 hypersensitivity?
- Transfusion of mismatched blood type
- Autoimmune hemolytic anaemia
What does type 3 hypersensitivity involve?
reactions against soluble antigens circulating in serum.
What do antibody-antigen immune complexes deposited in organs in type 3 hypersensitivity reactions lead to?
– Complement activation
– Neutrophil recruitment
– Inflammation-mediated damage
What are examples of type 3 hypersensitivity?
– Arthus reaction
– Serum sickness
– Oral erythema multiforme (EM)
What is Arthus reaction?
hypersensitivity reaction where antibody-antigen complexes are localised (e.g blood vessel walls)
What can Arthus’s reaction arise from?
injected particles (booster vaccines)
inhaled or ingested allergens
What is serum sickness?
systemic form of Arthus reaction
complexes lodge in many different tissues
What is oral erythema multiforme characterised by?
crusty blistering of oral mucosa
What is oral erythema multiforme caused by?
deposition of immune complexes (IgM immune complexes) in the microvasculature of the oral mucous membrane
What can oral erythema multiforme arise from?
acute inflammatory response to HSV
hypersensitivity to drugs e.g Trimethoprimsulfamethoxazole
What is trimethoprimsulfamethoxazole administered for?
to treat urinary or lower respiratory tract infections.
What’s type 4 hypersensitivity?
T cell-mediated hypersensitivity (no antibodies)
What is type 4 hypersensitivity sometimes called?
Sometimes called delayed hypersensitivity as takes time to recruit T cells (adaptive immune response)
What cells does type 4 hypersensitivity involve?
CD4+ T cells (inflammation induced damage via macrophages)
CD8+ T cells (direct damage of cells – cytotoxicity)
What are examples of type 4 hypersensitivity?
- Contact dermatitis
- Tissue graft rejection
- Response to intracellular pathogens (e.g., TB) – characterised by the formation of granulomas in lung tissue.
- Oral diseases – Orofacial granulomatous (OFG)
What happens in contact dermatitis?
Localized T cell reaction at site of antigen exposure
