Hypersensitivity II

Second post on hypersensitivity! In this post, I will cover Types II, III and IV. (To learn about type I hypersensitivity, please see my first post on the topic.)

Type II Hypersensitivity

While Type I Hypersensitivity is IgE-mediated, type II hypersensitivity is IgG mediated. IgG reacts to the cell surface antigens of the target cell, attracting complement and NK cells, which result in inflammation and tissue injury. These reactions are a bit slower than Type I reactions, taking around 30-60 minutes.

A typical type II hypersensitivity reaction occurs when an incompatible blood group is given. I've already spoken about blood groups here.

Type III Hypersensitivity

Type III hypersensitivity, like type II hypersensitivity, is mediated by IgG. In this case, however, IgG binds to soluble antigens (not membrane-bound antigens), forming an "immune complex" made up of several antigens and antibodies. Usually, immune complexes can be cleared by macrophages, but in the case of type III hypersensitivity, the immune complexes are of an "awkward size," making it hard for macrophages to eat them up. This causes activation of complement and thus inflammation, or occlusion of blood vessels due to the size of the complexes. Type III hypersensitivity reactions are even slower than type II reactions, taking around 2-6 hours.

One example of type III hypersensitivity is the Arthus reaction, which is used to test for tetanus antibodies. A subcutaneous injection of antigen is given, and if antibodies are present, localised cutaneous vasculitis (inflammation of blood vessels) occurs.

Another example is "farmer's lung," which is caused by antigens from hay dust which deposit in the walls of the alveoli. This can be distinguished from bronchial asthma (a type I hypersensitivity reaction) by the type of antibodies: bronchial asthma is IgE-mediated, whereas "farmer's lung" is IgG-mediated.

A third example is "serum sickness," which occurs after being given antiserum and can persist for weeks. A common method of producing antiserum against a toxin (from a venomous snake, for example) is to inject a horse with it (since horses are strong and can survive), take its antibodies, and give it to a patient. After the horse antibodies get rid of the toxin, there might still be some horse antibodies left over, which the body sees as foreign. Hence, you produce antibodies against the horse antibodies, causing systemic cutaneous vasculitis that can persist for weeks.

Type IV Hypersensitivity

Finally, we have type IV hypersensitivity, also known as Delayed-Type Hypersensitivity (DTH), which I've mentioned here and here. Type IV hypersensitivity is not mediated by antibodies- instead, it is mediated by T_H1 cells, cytokines and macrophages. Hypersensitivity reactions to poison ivy, as well as to metals like nickel and chromate, fall into this category. Another example is the tuberculin test. Type IV hypersensitivity reactions are the slowest of all, taking around two days to occur.

Type IV hypersensitivity reactions basically proceed the same way as other cell-mediated immunity pathways: an antigen is taken up by a professional antigen presenting cell and processed and presented on MHC-II to a T_H1 cell, which then, in conjunction with the pAPC, sends out a shitload of cytokines to activate macrophages and so on.

And that's it for hypersensitivity reactions! Let's round this off with a table:

Type	Mediated by	Length of time	Examples
Type I	IgE on mast cells	~20min	Allergic rhinitis Bronchial asthma Food allergies Skin prick test
Type II	IgG	30-60min	Blood transfusion reactions
Type III	IgG (Ab-Ag immune complexes)	2-6hr	Serum sickness "Farmer's lung" Arthus reaction (test for tetanus Abs)
Type IV	TH1, macrophages, cytokines etc.	~2 days	Tuberculin test Metal allergies Poison ivy hypersensitivity