L5 - Hypersensitivity Flashcards
What is a type I allergic reaction?
IgE-mediated
30 mins
e.g. allergic asthma
What is type II allergic reaction?
Cytotoxic reaction
days
IgG-mediated
e.g. drug allergy
What is type III allergic reaction?
Immune complex reaction
6-8h
IgG-mediated
e.g. allergic vasculitis
What is type IV allergic reaction?
T-cell mediated
28-72h
Th1/Th2/CTL-mediated
e.g. allergic contact eczema
What are general properties of allergens?
small
soluble
proteases
long lasting
mostly promote type-II response
Descrive protease mediated Type-1-IgE hypersensitivity
enzyme: Der p 1
cleaves occludin in tight junction
enters mucosa
dendritic cel primes in lymph node
Plasma cell travels back to mucosa
produce Der p 1-specific IgE antibodies
Der p 1-specific IgE binds to mast cell
triggers mast cell degranulation
What allergic responses can mast cells mediate?
oedema swelling
peristalsis
snotty nose
increase blood flow
What are IgE-mediated diseases?
systemic anaphylaxis
acute urticaria
hay fever
asthma
food allergy
What is IgE mediated reaction to inhaled allergen in the UPPER AIRWAYS?
rhinitis
What is IgE mediated reaction to inhaled allergens in the LOWER AIRWAYS?
Asthma
What reponse is T-bet crucial for?
Th1
What happens when you create a T-bet knockout?
get a Th2 response (Th1 usually inhibits Th2 response)
What happens during urticaria/anaphylaxis?
MAJOR lowering of blood pressure
airway constriction
swelling epiglottis
What is vibrational urticaria?
overly sensitive mechanotransduction = mast cell DEGRANULATION
OVER ACTIVATION OF GPCR - EMR2
mutations make receptor susceptible to lose N-terminus
How can allergic reaction be diagnosed
In vivo
in vitro - specific IgE, ELISA
What did the IgE response originally evolve to do?
expel/destroy helminth/protozoal pathogens
Why is allergy on the increase?
Th1 inflammatory immune defects rising
changes to clean environment in developing countries skews immune response to Th2
What is atopic dermatitis?
chronic inflammation
apoptosis of keratinocytes
Leaky skin binds keratin fibres together
What is Type II hypersensitivity?
Ig or IgM bind to cell surface Ab:
- activating complement
- bind Fc receptors on Tc and Nk cells - promote ADCC
lysis of Ab-coated cell
What are clinical examples of Type II responses?
Grave’ disease
- thyroid
Myasthenia Gravis
- Ach receptors
haemolytic anaemia
What are Type III diseases?
IgG immune complex deposition on vessel walls = Arthus reaction
Immune complex-mediated cytotoxicity
MOST DAMAGE STEMS FROM ACTIVITY OF NEUTROPHILS - difficult for neutrophils to phagocytose, still release LYTIC ENZYMES
What is Type IV hypersensitivity?
delayed hypersensitivity
What is allergic contact dermatitis?
Th1 cell mediated
Mediated via lipid soluble urushiol oil haptens binding MHCI - poison ivy complex
What is Coeliac disease?
villous atrophy
crypt hyperplasia
What is the allele that 95% of coeliac patients have?
HLA-DQ2 class II MHC allele
binds a-gliadin
What cellular destruction occurs in coeliac disease?
peptides produced from gluten do not bind MHC class II
enzyme tTg modifies peptide so they bind
peptide binds & activates gluten-specific CD4 T cells
activated R cells kill mucosal epithelial cells - binds Fas & also secrete IFN-y
Why does the cellular destruction of coeliac disease not happen with multiple food proteins?
protease resistant peptides may cause increase in IL-15 - induces NKG2D-ligands
increase intraepithelial lymphocyte mediated killing
