Allergic Diseases

Question 1

Allergy

Answer 1

Over reaction to harmless antigens

Question 2

Different types of hypersensitivity

Answer 2

I
II
III
IV

Question 3

Type I hypersensitivity

Answer 3

30 minutes

IgE mediated due to a soluble antigen, immediate, mast cell induced

Question 4

What does Type I hypersensitivity cause?

Answer 4

Allergic rhinitis, allergic asthma

Question 5

Properties of allergens

Answer 5

Mucosal exposure
Low dose
Small
Soluble
Long lasting in the environment
Promote a Th2 response
Often proteases (can break down tight junctions)

Question 6

Dust mites

Answer 6

Derp 1 is a protease in dust mite faeces (mites aren’t allergenic)
cleaves occludin in the tight junctions and can enter the mucosa
Taken up by DCs
TH2 priming leading to B cells, produce Derp1 IgE antibodies
IgE binds to FceRI receptor on mast cells - mast cell degranulate
Activates PAR receptors and cleaves IL-33

Question 7

Allergy leads to

Answer 7

Increased fluid secretion
Increased blood flow
Systemic anaphylaxis
Acute uticaria

Question 8

Asthma

Answer 8

IgE (Type I hypersensitivity mediated)
Rhinitis is the upper airways and asthma is the lower airways
Can lead to chronic remodelling of the lungs and fibrosis causing epithelial shedding

Treating acute asthma with Salbutimol to relax bronchioles
Treating chronic asthma with blue inhaler (Salbutimol) and brown inhaler (anti-inflammation steroids)

Question 9

Anaphylaxis

Answer 9

Vascular leakage
Swelling of the epiglottis
Drop in blood pressure
Cardiac arrest

Epinephrine relaxes smooth muscle

Question 10

Eosinophil role in allergy

Answer 10

Kill parasites by reacting towards opsonised parasites, has physiological function which explains allergy symptoms e.g fluid secretion to rid of helminth

Question 11

type 2 hypersensitivity

Answer 11

cytotoxic reactions, drug allergy
IgG mediated destruction of platelets/blood cells
complement mediated - lysis of host cells
ADCC
takes days
graves disease, haemolytic disease of newborns (Thrombocytopenia), haemolytic anaemia

Question 12

type 3 hypersensitivity

Answer 12

immune complex reaction - antigen binds IgG
complement activation, immune complex attracts neutrophils, release lytic enzymes, ROS
immune complex deposition on vessel walls
6-8 hours
serum sickness, arthritis

Question 13

type 4 hypersensitivity

Answer 13

48-72 hours
T cell mediated, delayed
allergen presented by DC, TH1 cell produces IFNy, CTL kill cells
tissue destruction
allergic contact dermititis - poison ivy proteins react with haptens - become immunogenic
bind MHC

coeliac disease - have antibodies against transglutamidase enzyme
have different HLA MHC allele
Intolerance: HLA-DQ2 MHC binds derivatised a-gliadin promoting T cells to destroy small intestine cells

Question 14

IgE

Answer 14

Atopic = IgE overexpression (atopic diseases from over-zealous IgE response)

binds to Fc receptor FcRI on mast cells
when allergen binds IgE, mast cell degranulates, releases histamine

Question 15

mast cell

Answer 15

degranulates
provides CD40-CD40L activation and secretes IL-4 to stimulate B cells to secrete more IgE
granules:
histamine, lipid mediators and enzyme
role is to increase blood flow, increase fluid secretion, increase mucous

Question 16

histamine

Answer 16

increases vascular permeability
smooth muscle contraction
anticoagulation
vascular leakage

Question 17

lipid mediators

Answer 17

prostaglandin
attract monocytes, neutrophils - inflammation
platelet activating factor

Question 18

enzymes

Answer 18

proteases

Question 19

gene defects highlighting mast cell importance

Answer 19

NLP3 mutant - no inflammasome
Hives due to over reaction of GPCR-EMR2 - important in mechanical stress sensing, but overly sensitive mutant induces mast cell degranulation

Question 20

Diagnosing allergies

Answer 20

In Vivo
- physiological evidence and skin prick test (injecting allergens into skin and looking for reaction)

In Vitro

• IgE assay to determine if patient is atopic
• Specific IgE tests to find specific allergens they bind to

Question 21

Treating allergies

Answer 21

• Antihistamines
• Corticosteroids (anti-inflammatory, brown inhaler)
• Desensitization therapy to block Th2 response
• Anti-IgE antibodies

Question 22

Cause of Type 1 hypersensitivity

Answer 22

Genetic susceptibility
- Atopic or not?

Environment

• early exposure to ubiquitous microorganisms; helminth infection; Hep A virus
• Commensal microbiota composition
• More hygiene = Atopic (less = non-atopic)

Question 23

Atopic Dermatitis (Eczema)

Answer 23

Chronic IgE-mediated inflammation causes keratinocyte apoptosis and barrier defects:

• leaky skin binds keratin fibres together
• allows allergens to reach DCs and antigens enter circulation