Allergy Flashcards
What is hypersensitivity? (1)
Harmful over reaction of the immune to non-self innocuous antigens
What are the different types of allergic reactions? (4)
Type I
Type II
Type III
Type IV
What is type 1 hypersensitivity? (5)
30 mins - rapid onset
IgE-mediated, immediate type hypersensitivity
(IgE-mediated degranulation of mast cells)
(e.g. allergic rhinitis, allergic asthma, urticaria)
Against soluble antigens which are recognised by IgE molecules
Fc region of the antibody binds to Fc areas found the allergy molecule
What is type 2 hypersensitivity? (6)
Days
IgG mediated destruction of blood cells/platelets
Cytotoxic reaction (complement lysis/ADCC)
Autoimmune haemolytic anaemia, Haemolytic disease of the newborn Thrombocytopenia.
Blood transfusion mismatch
(e.g. drug allergy)
What is type 3 hypersensitivity? (3)
Delayed - 6-8 hours
Mediated by IgG molecules
Immune complex reaction- complement activation
(e.g. allergic vasculitis
What is type 4 hypersensitivity? (3)
48 – 72 h
T-cell mediated, delayed type hypersensitivity
Dendritic cells take up soluble antigen and present it to T cells which cause cytotoxicity
(e.g. allergic contact eczema)
Organ manifestation of type I-allergic diseases (4)
Skin/Mucosa - 45%
Cardiovascular system - 10%
Gastrointestinal tract - 20%
Respiratory tract - 25%
What are the general properties of allergens (7)
Small 15-40,000 Mw proteins
Soluble
Long lasting in environment
Low dose of allergen
Mucosal exposure
Often proteases
Most allergens promote a Th2/type-II immune response
What is an example of type 1 hypersensitivity? (1)
Dust allergens
What are atopic diseases? (1)
Too much IgE response - type 1
Protease-mediated Type-I-IgE hypersensitivity (10)
Tight junction destruction and Der p 1 enters submucosa
Interacts with dendritic cell
Dendritic cell up regulates costimulatory molecules and present to naive T cell
Activation via costimulatory molecule and secretion of TH2 cytokines (such as IL4) causes naive T cell to become a TH2 cell
TH2 interacts with B cell
Undergoes class switching to produce IgE
Plasma cells produce too much IgE
Interacts with mast cell
Mast cell interacts with allergen via the antibody causing a conformation change - IgE binds to FceRI receptor on mast cells
Mast cell degranulates pre form protein from cytosol into extracellular environment
Protease allergens can potentially activate PAR receptors, and cleave IL-33
What are the different types of IgE mediated diseases? (6)
LOOK AT LECTURE SLIDE FOR TABLE
Allergic Rhinitis / Asthma (6)
IgE mediated reaction to inhaled allergens
upper airways: rhinitis
* nasal itch
* sneeze
* rhinorhoea
* nasal obstruction
lower airways: asthma
bronchoconstriction, mucus hypersecretion
* wheeze,
* breathlessness,
* cough
TH2 skewed disease
What is the important transcription factor in TH1 immunity? (14
T-bet
No t-bet - no TH1 response - airway remodelling (hyperplasia/hypertrophy/collagen deposition/epithelial shredding) TH2 skew (too much TH2)
Urticaria/anaphylaxis (6)
Swelling and histamine driven process
Direct/rapid route in to blood stream (sting, ingestion)
Catastrophic lowering of blood pressure, airway constriction,
swelling of epiglottis
Epinephrine relaxes bronchiole smooth muscle
Route and dose greatly affects potential outcomes
Mainly IgE mediated
Mast cell importance in urticaria (4)
Primary gene defects highlight this
Cold induced urticaria- triggered by NLP3 mutants (activates the inflammasome)
Vibrational urticaria over activation of the GPCR- EMR2
Truncation of inhibitory region PLCG2 (phospholipase enzyme involved in signalling)
Overly sensitive mechanotransduction induces mast cell degranulation
Eosinophils (3)
Normally kill parasites via reacting towards opsonised parasites.
However large amounts of IL-5/IL-3 in allergy cause degranulation
Airway remodelling eventually
Describe diagnosis (3)
In vivo - doctors inject an allergen and wait for a reaction
In vitro - look for total-IgE through ELISA test or look for specific molecules IgE is binding to
Describe treatments (4)
Antihistamines - block histamine receptor
Lipoxygenase inhibitor - produce leukotrienes and prostaglandins
Corticosteroids for long term chronic asthma - suppress immune response and inflammation from occurring
Treg cells
Why is allergy on the increase? (5)
Hygiene hypothesis - don’t have much of a TH1 response
Change to a clean environment in developed countries skews the immune response to a Th2 response
Not quite correct
Counter regulation hypothesis is more accurate - lack of T reg cells
Cow shit, rotten vegetables, and worm parasites are good for you
What are the causes of type 1 hypersensitivity (2)
Genetic susceptibility
Environment
What are the genetic factors that trigger atopic diseases? (3)
Anything that skews TH1 response to TH2 response - increase in cytokines, defects in transcription factors
Atopic dermatitis (3)
Chronic inflammation (initiated via IgE), apoptosis of keratinocytes
Leaky skin (filaggrin defect) binds keratin fibres together (leaky skin-allergens)
Describe Type II Hypersensitivity: Antibody-mediated cytotoxicity (10)
Results when Ig or IgM bind to cell surface Ag
– Activating Complement
– Binding Fc receptors on Tc and NK cells cells promoting ADCC
* Both processes result in lysis of the Ab-coated cell
* Clinical examples of Type II responses include:
– Certain autoimmune diseases where Abs produced against membrane
Ag
* Grave’s Disease –thyroid hormone receptor
* Myasthenia Gravis –acetylcholine receptors
* Autoimmune hemolytic anemia – Ab’s produced vs RBC membrane Ag’s
– Hemolytic Disease of the Newborn
– Hyperacute graft rejection
* Blood Transfusion, Graft rejection
- Drug induced thrombocytopenia
Type III Hypersensitivity: Immune Complex-mediated cytotoxicity (7)
Caused by immune complex deposition in tissues
– Fc mediated
– Activates complement which attracts neutrophils and stimulates
mast cell degranulation
– Depending on location, rxn can be localized or systemic
* Most damage stems from activity of neutrophils
– Immune complexes can adhere to tissue making it difficult for
neutrophils to phagocytose
– Neutrophils continue releasing lytic enzymes, etc
Stages of delayed hypersensitivity (4)
APC take up antigens
Interact and activate T cells
TH1 cells activate immune response Cause inflammatory response and T cell mediated cell death
Give examples of type 4 hypersensitivity (3)
Insect venom
Tuberculosis tests
Coeliac disease (4)
T cell activation of things that are completely harmless/should be harmless in terms of gliding proteins found in gluten protein
MHC class 2 molecule present alpha-gliadin peptide molecule which activates T cell
T cells cause immune response and can cause destruction of gut lining
