11. Allergy: Immune Misbehaviour

Question 1

What is allergy?

Answer 1

Inappropriate immunity

Question 2

What are the 4 main types of hypersensitivity?

Answer 2

An immune response to the wrong stimulus, for the wrong amounts or for a right stimulus in the wrong place.

Four categories but some may go between categories

I: IgE-mediated mast cell degranulation (most allergies - asthma etc)

II: Cytotoxic antibody against cell surface antigens (transfusion reactions, transplant rejection)

III: Immune complex mediated (e.g. SLE, serum sickness)

IV: Delayed type (DTH)(T-cell mediated)

Question 3

What is the allergy march?

Answer 3

Tendency if you have one allergy you will have other allergies

Question 4

How much IgE is present in serum?

Answer 4

100ng/ml - compared to IgG of 15mg/ml

2.5day half life

Question 5

Where is most IgE present?

Answer 5

Not in the circulation - goes into connective tissue where it is picked up by mast cells

Question 6

Where is IgE amounts elevated?

Answer 6

Parasitic diseases - clears parasitic worm infections (e.g. schistosomiasis)

Hyper-IgE syndrome - immunodeficiency disease w/ defective IFNgamma production, up regulating IL-4 which causes B cells to class switch to produce IgE cells

Allergy

Question 7

What cytokines promote IgE class switching and which inhibit?

Answer 7

Promote: IL-4 and IL-13
Inhibit: Gamma interferon (IFNgamma) from Th1 cells

Question 8

How does IgE bind to antigen in allergy?

Answer 8

IgE binds to high affinity Fc epsilon R1 on surface of mast cells - picks up IgE and binds to Fc part, if an allergen/antigen comes along that that IgE is specific for then linking together of two IgE antibodies by antigen - as these are bound to Fc epsilon R1 receptor they become cross-linked which causes a signalling cascade resulting in mast cell degranulation and inflammatory mediators released (histamine, serotonin, newly synthesised stuff too: TNF, prostaglandins, leukotrienes)

Different IgEs can bind to different epitopes on the same allergen/antigen

Question 9

How many house mites are present in an average mattress? What cause the allergic response?

Answer 9

200 million

House mite faeces, Der p1 mite allergen on faeces

Question 10

What is another name for Type I hypersensitivity? What occurs?

Answer 10

Atopy

Very rapid response followed by a late phase response

This results in recruiting of CD4+ helper T cells, monocytes, eosinophils

Question 11

Is there an ‘allergy gene’?

Answer 11

No, combination of many differing genes and environmental factors

Question 12

Which gene products influence susceptibility to asthma?

Answer 12

IL-13, IL-4, IL-4 receptor alpha chain, prostaglandin D synthase, TNF

Question 13

Is allergy actually increasing? Why?

Answer 13

Yes (not apparent increase, genuine increase), may be due to: Hygiene, barrier function (soap and shit)

Question 14

What occurs in the Hygiene hypothesis?

Answer 14

Higher amount of Th2 cells (produce IL-4, IL-13 for IgE class switching) due to lack of microbial stimulant when young

Question 15

What occurs in the barrier function hypothesis?

Answer 15

Washing damages skin barriers and diesel etc damage mucosal surfaces

Question 16

How may the environment cause allergies?

Answer 16

disruption of mucosal surfaces, antigen

Question 17

How do you treat allergen?

Answer 17

1. Avoid allergen exposure
2. Pharmacotherapy - corticosteroids, sodium chromoglycate, anti-histamines, montelukast - anti-inflammatories etc not specific
3. Immunotherapy - give incredibly small amounts of allergen to person increasing allergen amount over a period of time

Question 18

What is SLIT?

Answer 18

Sub lingual immunotherapy - less time, fewer side effects than regular immunotherapy

Question 19

What is omalizumab?

Answer 19

An anti IgE antibody which recognises IgE and clears it, also reduces amount of Fc epsilon R1 due to feedback mechanism (more IgE=more Fc epsilon R1)

Question 20

How does Type II hypersensitivity occur?

Answer 20

IgG binds to antigens on surface of cell, along comes Killer cell (cells that participate in Antibody dependent cellular cytotoxcitiy - only need Fc receptor) which kills cell

Question 21

What happens in haemolytic disease?

Answer 21

Mother lacks rhesus D, baby has rhesus D, during childbirth mother makes anti-D (anti rhesus D) IgG’s when blood and shit get everywhere - this is not a problem though as mother and baby are separated.

Becomes problematic after first pregnancy due to sensitisation, stimulates memory cells which can cause haemolytic disease in newborns.

This is solved with rhesus D prophylaxis - mothers given IgG anti to wipe up all IgG anti-D

Question 22

What is type III hypersensitivity?

Answer 22

Deposition of Immune complexes into places with limited space (e.g. kidney, skin) and cause inflammation - results in platelet aggregation and macrophage activation (and loads of other stuff which damages tissues) - basically sets the whole shebang off (IgE mediated response=inflammation)

SLE (systemic lupus erythematous) - build up in places

Serum sickness

something else

Question 23

How is type IV different to the other types? Give examples

Answer 23

Mediated by T cells not antibody, much slower reaction (T cells have to proliferate and differentiate)

e.g. tuberculin skin reaction, contact dermatitis to nickel/poison ivy

Question 24

How does Type IV fuck shit up?

Answer 24

Sensitised T cells start to secrete cytokines activation eosinophils/macrophages. Eosinophils cause tissue damage. Macrophages enlarge and become giant cells caused by macrophage fusion or appear as epitheliod cells which combined form granulomas and cause damage.

Question 25

What are innate hypersensitivity reactions?

Answer 25

Hypersensitivity based on innate response

e.g. infection with staphylococcus aureus which can provoke toxic shock syndrome