Hypersensitivity: Types

Type I - IgE mediated mast cell degranulation.

• On the surface of mast cells are Fc receptors that are specific for the IgE class of antibody.

• This is in fact the high affinity IgE receptor that’s called FcεR1.

• So this will bind IgE antibodies by the Fc region of the antibody; that’s why it’s called an Fc receptor.

• The problem arises, is if an antigen comes in which the IgE is specific for, and that antigen binds to the IgE.

• The IgE antibodies on the surface of the mast cell get linked together; we use the term cross-linked.

• If this substance is a completely innocuous substance, for example grass pollen, we refer to it as an allergen. I.e.
it’s going to generate allergy.

• The consequence of the IgE antibodies being linked together by the allergen is that the mast cells release their
granules, they degranulate.

Type II hypersensitivity - cytotoxic antibodies against cell surface antigen.

• Imagine a cell surface, with some antigens present on the cell surface, and antibodies are bound to those
antigens.

• Sometimes the antibodies can be directly toxic to the cell.

• However, in most cases, other components of the immune response are required in order for these antibodies to
actually damage the cell.

• So for example, the classical pathway of complement may become activated, leading to the production of the
membrane attack complex.

• Or killer cells, that is any cell that is able to participate in ADCC.

◦ So this term K-cell is used as a generic description of cells able to participate in ADCC.
◦ There’s only two things you need from a cell to do that:
‣ You need it to have an Fc receptor
‣ You need it to be able to produce toxic molecules.

• Or macrophages that again have Fc receptors on their surface and are able to attack the coated cell.

Type III hypersensitivity - immune complex mediated hypersensitivity.

• Immune complex, is simply an antibody bound to an antigen.

• In this situation, there is a binding to an inappropriate antigen or immune complexes are becoming trapped in
small tissue spaces in the body and causing pathology.

• For example, macrophages can become activated, complement can become activated.

• There will be recruitment of neutrophils if complement component C5a is generated, because that’s a very
potent chemotactic factor for neutrophils, and pathology will ensue.
Type IV hypersensitivity - delayed type hypersensitivity.

• It’s called delayed type hypersensitivity because it takes a little while to get going.

• The other three types, you can have antibody that's already present, and as soon as the antigen comes into the
body, the response will happen immediately.

• For T-cells, you need them to expand up in number, to proliferate, to differentiate, and to start secreting
cytokines.

• So typically, type IV hypersensitivity takes two or three days before you actually see any effects.

• There is recognition of peptide MHC Class II by the T-cell receptor on a T-cell that is going to mediate this
hypersensitivity reaction, most commonly by producing excessive amounts of cytokines.