Allergy, hypersensitivity and summary

Question 1

What is hypersensitivity?

Answer 1

Hypersensitivity refers to when your immune system reacts to substance strongly. Not all hypersensitivity is a true allergy.

Question 2

There are 4 classifications of hypersensitivity that defines the type of response you see in hypersensitive reactions. Name the 4 classifications.

Answer 2

1. Type I
   Atopic allergy
   (IgE mediated)
2. Type II
   - Immediate
   Complement
   mediated
   - Medium
3. Type III
   Serum sickness
   (Immune complexes)
   Medium
4. Type IV
   Delayed Type (DTH)
   Slow response

Question 3

List the 6 different types of type 1 allergy.

Answer 3

Asthma (1 in 6 New Zealanders)
* Allergic rhinitis (seasonal hay fever)
* Skin (dermatitis) Eczema, Urticaria (hives)
* Insect allergies (House dust mite, bee stings)
* Animal dander
* Drugs (penicillin)
* Large food proteins (gluten, peanut protein)
* Nickel (Metal induced contact dermatitis)
* Anaphylaxis – a serious complication

Question 4

Explain the process of 1. Type I
Atopic allergy.

Answer 4

In this process, mast cells get triggered by large pathogens such as parasites (that are too big to be engulfed by pathogens), the mast cell will react, then degranulation will occur. The antibody IgE will bind to the surface of the pathogen, the Fc region will bind to the FcεRI receptors on mast cells. This will trigger the mast cell,
rupture and empty their granules which contain histamine.

Question 5

What is so special about the FcεR binding to the Fc region on the IgE antibody?

Answer 5

The FcεR on mast cells has very high affinity towards IgE:antigen complexes, meaning binding strongly which means it sticks for a long time. But that is not so important. What is important is that IgE is now pre bound to the mast cell. So when you are exposed to it a second time, the reaction is much more faster and stronger as the mast cell is already sensitised.

Question 6

What does sensitised mean?

Answer 6

Sensitised refers to the immune system being previous exposed to the pathogen.

Question 7

When a mast cell degranulates, what substances does it release?

Answer 7

Histamine
Leukotrienes
Prostaglandins
Free radicals
Substance

Question 8

What triggers the type 1 hypersensitivity response?

Answer 8

Pollen grain – rhinitis
Dust mite – dust allergy
Peanuts - anaphylaxis
Bee venom - anaphylaxis

Question 9

What is Rh (Type 2)?

Answer 9

Rhesus factor (RhD) is an antigen
expressed on red blood cells. You are
either Rh+ (presence) or Rh- (absence). Sometimes mothers are born with Rh negative, meaning they don’t have it the protein.

Question 10

Describe Anti-RhD mediated haemolysis.

Answer 10

As the woman will give birth, the baby’s Rh positive blood cells will leak across the placenta into the mother’s bloodstream. The mother will sense this as foreign and makeanti-RhD IgG antibodies. The mother’s antibody will activate the complement system, which will result in the lysis of the RBC. It will also initiate FcR mediated phagocytic, destroying the RBCs.

Question 11

What happens when the phagocytes can’t engulf the RBC easily?

Answer 11

These phagocytes are called frustrated phagocytes which kill the RBCs. The process of the destruction of RBCs is Haemolysis.

Question 12

How to prevent haemolytic anaemia?

Answer 12

Inject the mother of anti-Rh globulin (RHOgam). This antibody will destroy any foetal RBCs in her blood, so that the mother’s antibody will not be able to create her own antibodies against the Rh+. That way, infuture pregnancies, shewon’t attacka Rh-positive baby’s red blood cells.

Question 13

What is type 4 hypersensitivity?

Answer 13

This is a delayed sensitivity mediated by T cells.

Question 14

What is an example of type 4 hypersensitivity?

Answer 14

The bacterium of TB. Basically you need to inject a small amount of PPD (Purified Protein Derivative) just under the skin. Wait 48/72 hours and the patient will have a lump on their arm. If there is a big bump, then there is active TB. This is because the T cells have reacted to it.

Question 15

Explain the concept of allergic desensitisation.

Answer 15

Desensitisation Therapy for Allergies is a way to reduce allergic response. When you have an allergic response, your immune system makes IgE antibodies, which stick to mast cells and cause allergic reaction. However, desensitisation occurs when you make the B cells generate and IgG response instead of IgE. Because of this, you will have enough IgG that will bind to the allergen, blocking the IgE to bind to it, reducing allgeries. Example would be scratch test. There must be high affinity of the IgG bIgG that competes with IgE.

Question 16

What are monoclonal antibodies (MAB)?

Answer 16

A lab-made antibody that is identical (all copies are the same) and are specific to one antigen.

Question 17

How to make a monoclonal antibody

Answer 17

1. Immunise the mouse with the antigen
2. Mouse starts producing antibodies to fight off the antigen
3. Spleen of the mouse is taken out and mushed up. You mix this with Mouse myeloma line. You also add this compound called Polyethylene Glycol
   (PEG)
4. This causes the membrane to diffuse and form the hybrid called hybridoma (genes from spleen + genes from myeloma line).
5. Take the hypridoma onto a ELISA screen where they grow rapidly.
6. And then When you add antibodies from a sample, if they bind the antigen, a color change occurs after adding a reagent. This color change shows that antibodies are present and reacting to the antigen.

Question 18

Where are mast cells located?

Answer 18

Skin

Question 19

What is Anaphylaxis?

Answer 19

Anaphylaxis is a serious complication when the mast cell activation occurs throughout the
body.