Lec 25 - Allergy and hypersensitivity

Question 1

What is allergic rhinitis?

Answer 1

Seasonal hayfever- out throat becomes scratchy and our nones are runny due to out nose, throat and upper respiratory tract undergoing an allergic response

Question 2

What are the four classes of hypersensitivity?

Answer 2

Type I = Atopic allergy (IgE mediated) immediate response
Type II = complement mediated - medium response
Type III = Serum sickness (immune complexes) medium response
Type IV = Delayed type (DTH) - Slow response

Question 3

Compare the quickness of the responses for Type I and Type IV hypersensitivity responses?

Answer 3

Type I response is within minutes,
Type IV can take between 48 and 72 hours

Question 4

What is the role of Mast cells in hypersensitivity/allergic responses?

Answer 4

When challenged, they release granules, which consist of very potent inflammatory mediators which immediately cause type I hypersensitivity

Question 5

Describe the process of a mast cell in hypersensitivity type I

Answer 5

IgE recognises antigens on the surface of parasites, which then attract the mast cells, which then bind the FC region of the IgE, which triggers the mast cell to burst open and degranulate, releasing the powerful inflammatory mediators

Question 6

Name the four most common things the IgE molecules will respond to (allergens)

Answer 6

Bee venom
Peanuts
Dust mites
Pollen

Question 7

Why do some people have allergies and some don’t?

Answer 7

Some people’s immune systems produce B cells instead of producing IgG, which is what you want.

Question 8

Describe the process of type I hypersensitivity

Answer 8

An allergen binds to a B cell receptor, which triggers a B T cell interaction, and the T cell interacts with the MHC on the B cell while the B cell is processing the allergen. T cell produces a cytokine called IL-4, which drives the B cell to use IgE over IgG. So we end up with B cells with IgE maturation and plasma cells. Plasma cells release IgE (in low levels but IgE is potent) that bind to Fc receptors for IgE on mast cells, which triggers degranulation

Question 9

What is a B cell receptor?

Answer 9

An antibody on the surface of a B cell - in this case IgM

Question 10

In type I hypersensitivity, which sub-subtype of T cells typically are involved?

Answer 10

Th1 or Th2 of CD4 helper cells

Question 11

Which Ig molecule typically acts as a B cell receptor in the process of type I hypersensitivity?

Answer 11

IgM

Question 12

What is type I hypersensitivity primarily driven by?

Answer 12

The high affinity that the Fc epsilon receptor on a mast cell has for IgE

Question 13

What are the 6 things a mast cell can stimulate by degranulising?

Answer 13

Smooth muscle
Blood vessels
Platelets
Mucous gland
sensory nerve endings
eosinophils

Question 14

What are the two surface toxin receptors on a neutrophil?

Answer 14

And Fc receptor (that binds to the back end of an Ig molecule)
The complement receptor (C3 receptor)

Question 15

What causes rhesus baby?

Answer 15

Caused by a blood group antigen RHD on the surface of red blood cells. Happens because the mother develops an antigen to the RHD antigen, and those antibodies with cause hemolytic anemia

Question 16

In order to prevent Rhesus baby, what RHD status should both the mother and father have?

Answer 16

The mother should be RHD- and the father should be RHD+

Question 17

Is rhesus baby a type of type I or type II hypersensitivity?

Answer 17

Type II

Question 18

How can we try and treat people with allergies?

Answer 18

Give them the allergen and increase the dosage over 12-24 weeks, and this drives the B cells to have a higher affinity towards IgG molecules over IgE. (works in 50% of patients)

Question 19

Describe the process of testing for tuberculosis and what type of hypersensitivity can it illicit?

Answer 19

Injection of small amount of protein PPD under the skin, wait 48-72 hours so hypersensitive response the kick in, and depending on the welt size we can see if the patient has TB or not. (if it exceeds a certain size, the patient either was or still is infected with TB)

Question 20

How are monoclonal antibodies formed?

Answer 20

An antigen is injected into mouse
More antigen is injected into mouse (boost)
The mouse is killed and splenocytes (cells filled with B cells) are extracted
Mouse myeloma (immortalised B cells) are also extracted
Hybridomas are formed between mouse B cells and myeloma forming immortalised fused B lymphocytes)
Mixing of these hybridomas with the antigens cause formation of monoclonal antibodies specific to a single antigen

Question 21

What are the advantages of monoclonal antibodies?

Answer 21

Highly specific for intended target
humanised so they can stay in the bloodstream for months
Tailor-made to just the right affinity
no adverse reactions to the antibody
can be bi-specific

Question 22

What are disadvantages of monoclonal antibodies?

Answer 22

Expensive to develop, side effects can occur