Lecture 25: Allergy, hypersensitivity and review.

Question 1

What are the major types of type one allergies?

Answer 1

• Asthma
• Allergic rhinitis (seasonal hay fever)
• Dermatitis
• Eczma
• Gluten and peanuts

[Just know a few]

Anaphylaxis is a serious complication

Question 2

What are the four classifications of hypersensitivity?

Answer 2

Type 1 - Atopic (immediate)
Type 2 - Complement mediated (medium)
Type 3 - Serum sickness (medium)
Type 4 - Delayed type (Slow response)

Question 3

Describe the type 1 atopic allergy reaction:

Answer 3

Resting mast cell can become activated and released factors such as:

• Histamine
• Luekotrienes
• Prostaglandins
• Free radicals
• Substance P

Question 4

What sorts of things can initiate a type one atopic allergy?

Answer 4

Pollen grain -rhinitis
dust mite - dust allergy
peanuts - anaphylaxis
Bee venom - Anaphylaxis

Question 5

Describe how type 1-atopic allergy occurs:

Answer 5

Fc(epsilom) receptor on mast cells has very high affinity towards IgE:Antigen complexes

When IgE binds large complex antigens i.e pollen it triggers local mast cells to rupture and empty their granules.

Powerful inflammatory mediators are released causing an allergic reaction. This causes immediate type (type 1) hypersensitivity.

Question 6

What does type 2 hypersensitivity involve?

Answer 6

FcR, complement and neutrophils

Question 7

Describe type 2 hypersensitivity:

Answer 7

Neutrophils have an FcR (Fc receptor, for the Fc region on antibodies) and C3 receptor (compliment receptor).

In type 2 hypersensitivity there is an antibody for example (but not exclusively) Anti-RhD (auto-antibody against rhesus factor on blood cells).

The neutrophil binds the anti-rhd which has bound RBC. However, RBC are too big to phagocytose so they end up releasing their lysosomes and forming wholes in the membranes of RBC leading to acute haemolytic aneamia and newborns are very sick.

Question 8

What is the mechanism of rhesus anaemia?

Answer 8

In pregnant mothers they can be RHD negative but their babies can be RHD positive because dads. The mother can produce anti-RHD IgG antibodies. These facilitate the type 2 hypersensitivity reaciton

Question 9

How can allergies be treated?

Answer 9

Desensitisation

Question 10

Describe desensitisation:

Answer 10

Works in about 50% patients

• Skin pricks to identify allergens
• Increased dose of allergen every 12-24 weeks to increase high affinity IgG that competes with IgE stopping the hypersensitivity reaction.

Question 11

What are monoclonal antibodies?

Answer 11

The sequestering of specific antibodies to use in treatments i.e anti-TNF (antibodies) use in rheumatoid arthritis to use the immune system to lower the levels of TNF reducing the pathology of rheumatoid athritis

Question 12

How are monoclonal antibodies made?

Answer 12

• Immunise antigen into the mouse
• Boost this with another dose (second exposure = larger response)
• Isolate the splenocytes (contains B lymphocytes)
• Fuse these with PEG to produce a hybridoma (immortalised fused B lymphocytes i.e they continuously divided)
• ELISA screen (to ensure its exactly whats wanted)
• Isolate the monoclonal antibodies

Question 13

What are the pros of using monoclonal antibodies?

Answer 13

• Highly specific for the intended target so no ‘off target effects
• Can be tailor-made with just the right affinity
• Humanised so they stay in the blood stream for months
• no adverse reactions or toxicity to the antibody
• Can be modified to be ‘bispecific’ for even greater potency

Question 14

What are the cons to monoclonal antibodies?

Answer 14

• Expensive to develop and make commercially

- Side effect of their function can be serious

Question 15

Summarise type one hypersensitivity reactions:

Answer 15

• Immediate
• Mediated by IgE and mast cells with high affinity FcR
• Allergen triggers mast cell degranulation and toxic chemicals induce a local inflammatory response
• Histamine is main culprit (antihistamines inhibit)
• Anaphahylaxis is serious complications when mast cell activation occurs throughout entire body.

Question 16

What is the hygiene hypothesis?

Answer 16

Argues that children are not challegened appropriately with old germs and develop an imbalanced Th2 mediated antibody response with fewer regulatory T cells.

Partly proven but the use of parasitic worms to treat autoimmune diseases of the gut.

Question 17

What is the TH1 and TH2 paradigm?

Answer 17

Th1 and Th2 paradigm is used to explain why allergies and autoimmune diseases are more prevalent in industrialised countries.

Th1 (CD4 subtype) is promoted following intracellular pathogen infection, this assists in an environment to kill intracellular pathogens

Th2 (CD4 subtype also) is promoted to control parasite infections and promote tissue repair during the resolution phase after an infection.

An imbalance can result in an exaggerated response to pathogens i.e allergies. (Th1 favoured)