Basics of Hypersensitivity

What is Hypersensitivity?

Hypersensitivity is when the body’s immune system responds in an exaggerated/inappropriate way. This response causes harm to the body in some way. This includes both allergy, attack of non-self antigens, and autoimmunity, attack of self-antigens that are no longer being identified as self.

It usually develops on the second exposure to an antigen, once the body has been primed.

Types of Hypersensitivity

There are FOUR types of hypersensitivity reaction:

• Type I – Immediate
• Type II – Cytotoxic
• Type III – Immune Complex
• Type IV – Delayed

Types I-III are all antibody mediated while Type IV is cell-mediated.

Type I

Type I is referred to as immediate hypersensitivity, or more commonly as anaphylaxis. It has a rapid onset and is mediated by IgE. It usually has a widespread effect on the body. Type I hypersensitivity relies on the body being exposed to an antigen, priming mast cells.

On first exposure to the antigen:

• Antigen Presenting Cells (APCs) detect the antigen and neutralise it.
• APCs present to B Cells which produce specific IgE antibodies for future defence
• IgE antibodies bind to Fc receptors on the surface of mast cells – priming the mast cells.

The crucial aspect of mast cells is that they contain histamine granules and when triggered, this histamine is released.

Upon second exposure to the antigen:

• Antigen binds to IgE on the mast cell surface.
• Mast cell degranulation occurs – histamine is released, along with other chemicals including leukotrienes.
• Histamine has multiple effects on the body including vasodilation, oedema, bronchospasm and an urticarial rash.

Type I hypersensitivity includes things like allergies e.g. latex, peanuts etc. Management involves avoiding the trigger, anti-histamines, corticosteroids to suppress the immune system and adrenaline in emergencies.

Type II

Type II hypersensitivity is where antibodies are produced against the body’s own antigens (auto-antibodies). This can occur due to self-antigens mutating. As compared to Type I, it is primarily mediated by IgG and IgM. The antibodies produced will trigger cell damage and inflammation through various methods.

Auto-antibodies can bind to antigens and trigger T Cells and macrophages to kill the target cell (hence cytotoxic). The complement cascade is also activated leading to two primary effects:

• Inflammation
• Membrane Attack Complex (MAC) – C5-9 will destroy cells directly.

Examples of Type II hypersensitivity include autoimmune disorders such as pemphigus and pemphigoid.

Type III

This is referred to as immune complex-mediated. These immune complexes are formed by the combining of antigens and antibodies. These complexes can then be deposited throughout the body, including in blood vessels.

The diagram above demonstrates Type III hypersensitivity. The deposition of immune complexes triggers inflammation, complement binding and platelet aggregation. Part of the sequence triggers vascular permeability which then stimulates further immune complex deposition. Neutrophils fail to remove the complexes but release damaging chemicals in the process.

An example of this includes erythema multiforme.

Type IV

This is referred to as the delayed hypersensitivity. It is mediated by T Cells rather than antibodies and leads to a more localised and slower response.

The mechanism for Type IV is quite complicated but can be summarised as below:

• The antigen is identified and processed by an antigen presenting cell (APC) e.g. Langerhans cells
• The APC travels to lymph nodes and presents the antigen to immature T Cells
• Memory T Cells and Cytotoxic T Cells are produced, specific for this antigen. This is sensitisation.
• Re-exposure to the antigen leads to it being processed by APCs but also being detected by the memory T Cells
• Activation of the memory T Cells, along with the production of chemokines, causes the production of pro-inflammatory cytokines
• Neutrophils, and eventually T Cells, are attracted to the area. Substances produced from these cells will cause damage to the tissue

Examples include lichenoid reactions and lichen planus.

Summary

• Type I – IgE mediated, immediate, mast cells and histamine. Example – latex allergies.
• Type II – IgG/IgM mediated, self-antigens and auto-antibodies. Example – pemphigus.
• Type III – immune complex-mediated. Example – erythema multiforme.
• Type IV – cell-mediated, delayed response, T Cells target antigen. Example – lichen planus.

References and Recommended Reading

• Basic Sciences for Dental Students
• Roitt’s Essential Immunology 13E (Essentials)