Lung immunology

Question 1

what is allergy?

Answer 1

Allergy – exaggerated immunological response to a foreign substance (allergen) which is either inhaled, swallowed, injected, or comes in contact with skin/eye.

o Allergy is a MECHANISM, not a disease.

Question 2

what is hypersensitivity?

Answer 2

Hypersensitivity – exaggerated response

Question 3

define intolerance

Answer 3

Intolerance – inability to consume or absorb/metabolise nutrients.

Question 4

define atopy

Answer 4

Atopy is the hereditary predisposition to produce IgE
antibodies against common environmental allergens

The atopic diseases are allergic rhinitis, asthma and atopic eczema

Allergic tissue reactions (in atopic subjects) are characterised by infiltration of Th2 cells and eosinophils

Question 5

What can MPPtype2 cell differentiate into?

Answer 5

The MPPtype2 cell can then differentiate into either the mast cell, basophil or macrophage under influence by cytokines.

Question 6

What are IgE-mediated allergic reactions in the upper/lower airway?

Answer 6

Both systems can act in the chronic or acute pathways.
In the chronic pathway, CD4+ Th2 cells can stimulate:
o IL-4 —-IgE synthesis.

o IL-5 —Eosinophil development.

o IL-9 —-Mast cell development.

o IL-13 —-IgE synthesis and airway hyperresponsiveness.

Question 7

what atopic diseases are included and what are they characterised by?

Answer 7

Atopic diseases include:

o Allergic rhinitis.
o Asthma.
o Atopic eczema.

Atopic allergic reactions are characterised by infiltration of Th2 cells and eosinophils.

Question 8

what is allergic march

Answer 8

“Allergic March” describes the common progression from atopic dermatitis to allergic asthma (link has recently been found between the two).

Question 9

what does hay fever effect and what are some causes?

Answer 9

Allergic Rhino-conjunctivitis (seasonal and perennial) affects up to 17% of the population à THIS IS HAYFEVER.

• Allergens vary from grass pollens, tree pollens, weed pollens and fungal pollens (the levels of which vary from season to season).

Question 10

what affects asthma and what are some causes?

Answer 10

Asthma is a very heterogeneous disease (many phenotypes):
o Intermittent, mild, allergy frequently important.
o Persistent, manageable, allergy often important.
o Chronic/severe, infection (not allergy) important.
* Symptoms of asthma include cough, dyspnoea, wheezing, chest tightness and secretions (due to bronchoconstriction).

Question 11

what is anaphylaxis and what are the common symptoms?

Answer 11

General symptoms are displayed on the left.

• Causes include:
  o Drugs (e.g. penicillin).
  o Foods (e.g. nuts, milk, eggs fish etc.).
  o Insect stings and latex.
• Relief though epinephrine injections.
• There is an overlap of atopic diseases such as hay fever AND asthma.
  an acute allergic reaction to an antigen (e.g. a bee sting) to which the body has become hypersensitive

Question 12

what does extrinsic allergic alveolitis affect?

Answer 12

affects lower/distal airways.

Question 13

what is the EEA mechanism of action?

Answer 13

1. Small allergen particles enter the alveolus and pass into the interstitium.
2. Allergic responses occur when antibodies bind to the allergens and stimulate a DTH response.

Question 14

what are some reasons as to why allergies are on the increase?

Answer 14

Factors could be microbial:

o Water sanitation (less oro-faecal infections).
o Food quality (lack of fermenting bacteria).
o Poverty (high asthma rates in urban).
o Medical intervention.

• Factors could be non-microbial:

o Pollution (air, water, food).
o Diet and nutrition (lack of Vit-D, fish oil etc.).
o Obesity.
o Stress.
o Bad genes.

Question 15

what will happens with allergen-injection immunotherapy?

Answer 15

• Over a long period of time, levels of Th2 drop while levels of Th1 and TReg cells increase.
• This changes the profile of cytokines which reduces the allergic response

Question 16

What provides immunity against viruses, bacteria, fungi and protozoa?

Answer 16

Th1, Th17, TK cells, IgM, IgA and IgG antibodies

Question 17

What provides immunity against helminth and ectoparasites?

Answer 17

Th2, IgE, IgG1 antibodies and other leukocytes

• Parasitic helminths or allergens induce epithelial cells to produce cytokines to stimulate 3 populations of cells to produce more cytokines.
• These cytokine combinations stimulate eventual parasite expulsion

Question 18

What are the principles of treatment of allergic airway disease?

Answer 18

1. Allergen avoidance.
2. Anti-allergic medication.
3. Immunotherapy - desensitisation/hyposensitisation.
   (Allergen-injection Immunotherapy)

Question 19

What are the advantages and disadvantages of allergen-injection immunotherapy?

Answer 19

Advantages - effective, produces long-lasting immunity.

Disadvantages - occasional anaphylaxis, time-consuming, standardisation problems

Over a long period of time, levels of Th2 drop while levels of Th1 and TReg cells increase.
This changes the profile of cytokines which reduces the allergic response.
These ideas were brought in by Leonard Noon and John Freeman.

Question 20

What is SCIT?

Answer 20

SCIT - Specific immunotherapy by sub-Cutaneous Injection involves injections of increasing doses of allergen over a long period of time to desensitise - could shift Th2 to Th1 profiles.