Hypersensitivity Flashcards
What is hypersensitivity? (1)
Harmful over reaction to non-self innocuous antigens
What is type 1 hypersensitivity? (3)
Atopic diseases caused by individual tendency to mount over zealous IgE responses
IgE-mediated degranulation of mast cells
Degranulation has various effects - increase in mucus production, vascular leakage etc
Immediate (within 30 mins)
What is type 2 hypersensitivity? (3)
Cytotoxic reaction (complement lysis/ADCC)
e.g. drug allergy
IgG/IgM mediated
Takes days
What is type 3 hypersensitivity? (3)
Immune complex reaction (complement activation)
IGg mediated
e.g. allergic vasculitis
6-8 hours
What is type 4 hypersensitivity? (3)
T-cell mediated, delayed type hypersensitivity
e.g. allergic contact eczema
48-72 hours
Organ manifestation of type I-allergic diseases (4)
Skin mucosa - 45%
Respiratory tract - 25%
Gastrointestinal tract - 20%
Cardiovascular system - 10%
How is type 1 hypersensitivity diagnosed (2)
Skin prick test - inject small amounts of allergens into skin and wait for histamine mediated response
In vitro - ELISA used to look for levels of IgE in the blood
Why are allergies on the increase? (2)
Hygiene hypothesis - exposed to less harmful pathogens, change to a clean environment in developed countries skews the immune response to a Th2 response
Counter regulation hypothesis - do not produce T regulatory cells due to living in a clean environment
Which hypothesis is more accurate: hygiene hypothesis or counter regulation? (1)
Counter regualtion
What are the causes of type 1 hypersensitivity? (2)
Genetic susceptibility
Environment
What are the genetic factors responsible for type 1 hypersensitivity? (4)
Genes triggering the immune response or directing CD4 TH cell differentiation
Genes regulating TH2 cell differentiation and effector afunction
Genes expressed in epithelial cells
Genes identified by positional cloning
What is affected by allergic Rhinitis and what are the symptoms? (5)
Mediated by antihistamines
Upper airways
- Nasal itch
- Sneeze
- Rhinorhoea
- Nasal obstruction
What is affected by asthma and what are the symptoms? (6)
Lower airways
- Bronchoconstriction
- Mucus hypersecretion
- Wheeze
- Breathlessness
- Cough
How to prove if it is a TH2 driven disease? (3)
Animal experiment - remove a gene and generate a knockout mice
Remove transcript factor for a particular T helper cell (TH1) - T bet 1
Produce more TH2 response
Leads to tissue remodelling - fibrosis
What is Anaphylaxis? (4)
Direct allergen injected into circulation
Activate mast cells and cause vascular leakage
Catastrophic lowering of blood pressure, airway constriction, swelling of epiglottis
What can be used to treat anaphylaxis? (1)
Epinephrine relaxes bronchiole smooth muscle
What are eosinophils? (2)
Normally kill parasites via reacting towards opsonised parasites
However large amounts of IL5/Il3 in allergy cause degranulation
Non-IgE allergic diseases-Type III (5)
Antibodies floating around
Antigen/allergen binds to it
Complement fixation
Produce C5a - anaphylatoxin
Cause degranulation of mast cells and recruitment of macrophage and neutrophils
Coeliac disease (3)
Microvilli destroyed
Lymphoid cells - important for reacting quickly against antigens - activated by dendritic cells
dendrite cells present antigen
T cells become activated and destroy mucosal surface
How does cellular destruction occur in coeliac disease? (4)
Peptides produced by gluten protein
Dendritic cell present on MHC class two cell
T cell activated and cause damage to mucosal layer by apoptotic ligands
ligands interact with mucosal cell and induce apoptosis
Mechanisms of treatments for allergic disease (5)
General anti-inflammatory effects
Induction of regulatory T cells
Inhibit effects of mediators on specific receptors
Inhibit synthesis of specific mediators
Bind to IgE Fc region and prevent IgE binding to Fc receptor on mast cells
Autoantibody target for autoimmune haemolytic anaemia (1)
Red blood cells
Example of type 2 disease (4)
Autoimmune haemolytic anaemia
Goodpasture Syndrome
Graves disease
Immune thrombocytopenia
Myasthenia gravis
Autoantibody target for goodpasture syndrome (1)
Glomerular basement membrane
Autoantibody target for graves disease (1)
Thyroid stimulating hormone receptor
Autoantibody target for immune thrombocytopenia (1)
Platelets
Autoantibody target for myasthenia gravis (1)
Muscle acetylcholine receptor
What kind of diseases do type 4 hypersensitive cause? (1)
Occupational diseases
