Lecture 25: Allergy and hypersensitivity

Question 1

What are the 4 classifications of hypersensitivity?

Answer 1

Type I - atopic allergy (IgE mediated) (immediate)
Type II - complement mediated (medium)
Type III - serum sickness (medium)
Type IV - delayed type (slow)

Classed based on speed

Question 2

What cells are involved in atopic allergies?

Answer 2

Mast cells

Question 3

How do allergic responses occur?

Answer 3

Mast cells have Fce(epsilon)R (Fc) receptors that have a high affinity towards IgE-antigen complexes. When IgE binds to large complex antigens, local mast cells rupture and empty their granules (cytotoxins) causing local inflammatory response

Question 4

What is the role of mast cells in allergic response?

Answer 4

They have Fc receptors that cause the mast cells to rupture (mast cell degranulation) when bound to IgE-antigen complexes and release cytotoxins

Question 5

What substances are released from rupturing mast cells?

Answer 5

Histamine (main)
Leukotrienes
Prostaglandins
Free radicals
Substance P

Powerful inflammatory mediators

Question 6

What type of antibodies are involved in allergic reactions? What is their significance?

Answer 6

IgE class antibodies - these are known to bind to large pathogens that cannot be destroyed by phagocytosis or enter cells

Question 7

How does one become allergic to substances?

Answer 7

A B cell binds to the allergen (pathogen) and displays a peptide on its MHC causing binding to a CD4 molecule of a helper T lymphocyte

This helper T cell causes B cells to produce IgE antibodies (should normally form IgG)

IgE antibodies will form complexes with pathogen and bind to Fc receptor on mast cells causing allergic response

Question 8

What is type II hypersensitivity?

Answer 8

Auto phagocytosis in which the antibody receptor and the C3 receptor recognise somatic cells as foreign and bind to cells releasing enzymes causing breakdown of membrane of cells.

Involves antibody, complement and neutrophils

Question 9

What is rhesus anaemia?

Answer 9

Condition caused by blood group antigen RhD on the surface of RBCs. Maternal antibodies developed to fetal RhD causes lysis of newborn RBCs

Question 10

What is RhD?

Answer 10

A blood group antigen found on the surface of red blood cells

Question 11

How does RhD occur?

Answer 11

RhD occurs when the father is RhD+ and mother is RhD -
This means the mother will not have RhD antigens and the fetus will have RhD antigens as the allele from the father is dominant

As the fetus develops in the mother, the mother’s immune system will recognise these RhD antigens from the babies RBCs as non-self and form anti-RhD IgG antibodies

These anti-RhD IgG antibodies will cause the lysis of the fetal RBCs.

Question 12

How can allergies be treated via desensitsation?

Answer 12

Increasing doses of allergen are injected into patient in to areas where there IgG antibodies will be produced instead of IgE

The IgG antibodies will compete with IgE preventing IgE from forming complexes with pathogen and causing mast cells to rupture

Question 13

How are monoclonal antibodies formed?

Answer 13

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

Question 14

What are advantages of the use of monoclonal antibodies?

Answer 14

Highly specific for intended target

Can stay in bloodstream for months

Question 15

What are disadvantages of monoclonal antibodies?

Answer 15

Expensive to develop

Side effects can occur