What are the different types of hypersensitivity reactions?


In this post, I want to discuss the different types of hypersensitivity reactions (HRs) I-IV. We’ll cover some pathophysiology as well as some examples of each.

Type I hypersensitivity reactions

A type I HR is what is typically referred to as an allergic reaction. Type I HRs are mediated by IgE antibodies that bind to Fc receptors on mast cells which causes them to degranulate and release histamine and other chemicals which are responsible for vasodilation, bronchoconstriction, anaphylaxis, and other signs and symptoms of an acute allergic reaction.

Because this reaction requires antibodies in order to cause a reaction, the patient will typically be fine during the first exposure to an allergen. After antibodies are created during the first exposure, and any subsequent exposures will cause the adverse and deleterious effects associated with allergic reactions.

Type I HRs are immediate reactions and often considered the most severe type of HR.

Examples of type I HRs include allergic reactions to foods or medicines such as a peanut allergy or a penicillin drug allergy. To relieve symptoms, the patient may require steroids, Benadryl, or epinephrine.

Type II hypersensitivity reactions

Type II HRs are often considered cytotoxic and alloimmune diseases. This is because the HR involves an immune response to the individuals own cells rather than a foreign antigen like in type I HRs.

There are a few types of type II HRs, and most involve a situation where an antigen is presented on a cell surface. This antigen is treated as foreign and the immune system ends up killing the somatic cell displaying the antigen. This can happen a few ways such as neutrophils, natural killer cells, cytotoxic T cells, or activation of the complement system and the membrane attack complex. In all of these ways, the immune system ends up killing the body’s own cells.

There is another type of type II HR that doesn’t involve cytotoxicity, but instead, inhibits proper cellular function through the use of antibodies that either block or inappropriately bind to cell receptors.

These reactions can minutes or hours to develop, and in some cases can continue for years in chronic diseases.

An example of a type II HR involving cytotoxicity is a transfusion mismatch reaction when transfusing blood products. Some examples of a type II HR that cause cellular dysfunction are myasthenia gravis and Grave’s disease.

Type III hypersensitivity reactions

Type III HRs are caused by circulating antigen-antibody complexes. These complexes initially float around in the blood but can become lodged in endothelial membranes of blood vessels and cause local immune responses at the site where they became dislodged.

Some examples of type III HRs are Raynaud’s syndrome where temperature-dependent antigen-antibody complexes become lodged in the capillaries and blood vessels of the fingers, leading to decreased circulation distal to the blockage, along with pallor, and coolness.

Type III HRs can take weeks to develop, and in some cases are chronic conditions.

Another example of a type III HR is systemic lupus erythematosus (SLE), although this is a mixed HR of type II and type III.

Type IV hypersensitivity reactions

Finally, type IV HRs are not antibody-mediated reactions but are cell-mediated instead. The cells involved are T and B cells that directly interphase with the antigen, creating antibodies and killing the foreign substance.

Type IV reactions typically are delayed reactions that may take 2-3 days to occur.

Examples of type IV hypersensitivity reactions are reactions to the tuberculin skin PPD test, where a local cell-mediated reaction may occur to the injection, involving an induration that is warm and hard to the touch. This is the result of a local inflammation response.

Videos to watch

I highly recommend watching a few short animated videos from Open Osmosis. They are incredibly helpful to learn the various HRs.