Allergy and the immune response

Question 1

Define: allergic response

Answer 1

Allergic reactions occur when an individual who has produced IgE antibody in response to an innocuous antigen, or allergen subsequently encounters the same allergen
Innocuous = non harmful antigen = dust, food allergen, medications

Question 2

Why are IgE response the most beneficial?

Answer 2

They are particularly beneficial in developing countries, because they can provide immunity against parasitic infections
- IgE mounts a greater response compared to IgG but having both against an infection is even more beneficial

Question 3

What is atopy and how many people suffer?

Answer 3

Atopy: genetic tendency to develop an allergic such as eczema - typically a heightened immune response to common allergens

In US and Europe almost half of the population have responses to one or more environmental allergens

Question 4

What is a type 1 hypersensitivity reaction?

Answer 4

IgE is the immune reactant and is produced by plasma cells - binds to FcR and cross links them on the mast cells
Soluble antigen
Effector mechanism - mast cells
Examples of reaction: allergic rhinitis, asthma, systemic anaphylaxis

lifespan in the serum is increased from days to months

Question 5

What is a type 2 hypersensitivity reaction?

Answer 5

Immune reactant: IgG
Antigen:
1) cell or matrix associated antigen
2) cell surface receptor

Effector mechanism:

1) complement , FCR+ cells (phagocytes, NK cells)
2) Antibody alters signalling

Examples:

1) drug allergies - penicillin
2) chronic urticaria (antibody against FCR1 alpha)

Question 6

What is a type 3 hypersensitivity reaction?

Answer 6

Immune reactant: IgG
Antigen:
soluble antigen

Effector mechanism:
complement phagocytosis (opsonisation) 

Examples:
serum sickness, Arthus reactions

Question 7

What is a type 4 hypersensitivity reaction?

Answer 7

Delayed type
Immune reactant: Th1
Antigen: soluble antigen
Effector mechanism: Macrophage activation
Examples: contact dermatitis, tuberculin reaction

Immune reactant: Th2
Antigen: Soluble antigen
Effector mechanism: IgE production, eosinophil activation and mastocytosis
Examples: chronic asthma, chronic allergic rhinitis

Immune reactant: CTL
Antigen: cell associated antigen
Effector mechanism: cytotoxicity
Examples: contact dermatitis

Question 8

Define: atopy

Answer 8

predisposition to allergic disease, due to high IgE and/or eosinophil levels

Question 9

What makes an allergen?

Answer 9

Protein- activate Th2 cells which drives IgE
Enzyme action- proteases are often allergens
Low dose- Favours IL-4/IL-13 which activates T cells to produce IgE (whereas high doses tend to induce IgG responses)
Low molecular weight- soluble in mucosa
Stable- can survive in desiccated particle
Can bind MHC - contains peptides that can activate T cells

Question 10

What cells initiate an allergic response?

Answer 10

DCs in the much initiate an allergic response

1) stimulates naive T cells
2) IL-4 released to induce Th2 cells
3) Th2 cells release more IL-4 which stimulates B cells to release IgE. They also release IL-3, IL-4, IL-5, IL-9, IL-13 which stimulates more Th2 cells, eosinophils, basophils

Question 11

What is sensitisation?

Answer 11

Repeated allergen exposure can cause sensitisation

Question 12

What do polymorphisms in the genes, MHC II, IL-4 and Fcepsilon R1 predispose people to?

Answer 12

Autoimmune responses

Question 13

What happens in IgE mediated reactions?

Answer 13

IgE binds Fcepsilon Receptor 1 on mast cells, activates eosinophils and basophils
Causes degranulation
Releases mediators - histamine

Question 14

What responses occur during systemic anaphylaxis?

Answer 14

Oedema
Increased vascular permeability 
Laryngeal oedema 
Circulatory collapse - hypotension 
Death

Question 15

What responses occur during acute urticaria?

Answer 15

Local increase in blood flow and vascular permeability

Oedema

Question 16

What responses occur during seasonal rhinoconjunctivitis (hay fever)?

Answer 16

Oedema of conjunctivitis and nasal mucosa

Sneezing

Question 17

What responses occur during asthma?

Answer 17

Bronchial constriction
Increased production of mucus
Airway inflammation

Question 18

What responses occur during food allergy?

Answer 18

Vomitting 
Diarrhoea
Pruritis
Urticaria
Anaphylaxis

Question 19

What are some of the mediators released during an allergic response?

Answer 19

Histamine
Cytokines - IL-1, IL-6, TNF-alpha
Leukotrienes, prostaglandins
Th2 cytokines - IL-4, 5, 13, GM-CSF

Question 20

What are the effects of histamine?

Answer 20

Smooth muscle constriction 
Bronchiole constriction 
Intestinal constriction (cramps, diarrhoea)
Vasodilation, swelling
Enzyme activation to break extracellular matrix and eosinophils

Question 21

What is the danger of a pre-existing IgE response to an allergen?

Answer 21

Can induce mast cell activation immediately

Question 22

What is the role of cytokines in terms of antibody production?

Answer 22

Different cytokines induce /inhibit class switching to different isotopes of antibodies

Question 23

Does environmental pollution increase allergies?

Answer 23

Huge amounts of pollution demonstrated greater lung injury in children but it didn’t demonstrate increased allergic responses

Question 24

When do allergies to food allergens occur?

Answer 24

They can develop at any age

Question 25

Are people predisposed to allergies?

Answer 25

Genetic polymorphisms - some people are predisposed to allergies such as hay fever and asthma which do appear to run in families

Question 26

What are the drug treatments for allergies?

Answer 26

Non-steroidal anti-inflammatories
Antihistamine
Steroids
Theophylline or epinephrine - prolongs or increases cAMP levels in mast cells, which inhibits degranulation

Question 27

What is immunotherapy in the treatment of allergies?

Answer 27

Desensitisation (skew to IgG)

Question 28

What is a blood transfusion reaction?

Answer 28

Type 2 reaction 
Acute <24 Hours 
- haemolytic
- febrile non-haemolytic
- urticaria 
- anaphylactic 

Delayed >24 hours

• haemolytic
• post transfusion purpura
• graft vs host disease

IgM ab in serum bind to Ags in RBCs from donor
= killing of RBCs via complement or antibody dependent cellular cytotoxicity

Question 29

What is immune complex disease?

Answer 29

IgG Abs bind allergens and form immune complexes (ICs)
- multiple ICs can get deposited onto the vasculature (vasculitis), joints (arthritis), kidney (glomerulonephritis), causing damage and inflammation

Phagocytes recognise ICs and engulf them- in case of phagocytosis dysfunction, can activate complement anaphylatoxins C3a, C4a and C5a

Question 30

What is delayed type hypersensitivity (DTH)?

Answer 30

> 24 hours

• Th1 cells can activate macrophages which cause tissue damage and granulomas in prolonged inflammation
• Th1 memory cells are activated and produce cytokines e.g IFN-gamma, TNF-alpha and beta which cause tissue destruction, inflammation
• IL-2 activates Th1 cells and CTLs
• chemokine recruit macrophages
• IL-3, GM-CSF for increase monocyte/macrophages

Question 31

What is contact dermatitis?

Answer 31

Infection or chronic exposure to antigen can cause this
- Dry skin: high water evaporation, mortar between cells is weak, skin flakes
- inflammation: inflammatory ells arrive leading to redness and swelling
both these effects lead to itchiness

Question 32

What is granuloma formation?

Answer 32

T cells surround infected or activated macrophages, trapping them and inducing the formation of multinucleate giant cells which cause tissue injury

Question 33

What does “ABCD” in hypersensitivity reactions mean?

Answer 33

Type 1: Allergic, Anaphylaxis and Atopy
Type 2: antiBody
Type 3: Immune Complex
Type 4: Delayed

Question 34

What does biphasic reaction mean?

Answer 34

once someone has had an allergic reaction they should be watched for 72 hours afterwards, as even once they have recovered from the first attack, they could undergo a second immune response

1 in 5 patients undergo biphasic reactions