The immune system protects the human body against disease by dispatching a bunch of immune cells, whenever the body encounters foreign material or antigens. These immune cells or effector cells elicit an inflammatory response in order to remove or eliminate these foreign antigens without causing much damage to the host.
However under certain conditions the host may elicit an exaggerated or an inappropriate immune response to a foreign antigen causing much damage to the host tissues. This exaggerated or inappropriate immune response is termed hypersensitivity.
Type I Hypersensitivity
Type I hypersensitivity is also termed as allergy and immediate hypersensitivity since symptoms manifest rapidly within minutes to hours. Antigens eliciting these allergic reactions are termed allergens and could be anything ranging from dust, food, pollen, drugs, insect products like bee venom, microbes and many different chemicals.
Certain individuals are genetically prone to develop Type I hypersensitivity reactions because they may inherit certain genes making them susceptible to this exaggerated immune response.
For example they may inherit certain MHC genes making their T-cells capable of recognising an allergen or they may have abnormally high levels of circulating IgE antibodies making them more prone to develop these reactions.
When an exogenous antigen or allergen is inhaled or ingested by a susceptible individual, circulating dendritic cells or antigen presenting cells(APC) may pick these allergens swim to a nearby lymphnode and present it over to CD4+ helper T-cells.
These T-cells are naive or inactive T-cells and an inactive or a naive T-cell could differentiate into an effector Th1 or a Th2 cell depending on the stimuli and the environment.
The naive T-cell after recognition of the antigen presented by the dendritic cell, in this case differentiates into an active effector Th2 cell. This may happen due to certain a cytokines like IL-4 present locally in the environment. IL-4 drives naive T-cells to differentiate into the Th2 subset.
On subsequent encounter with the antigen these activated Th2 cells produce a number of cytokines like IL-4, IL-5 and IL-13.
IL-4 besides stimulating differentiation of more Th2 cells also causes B-cells to class switch, meaning the B-cells instead of producing IgM antibodies now would produce antigen specific IgE antibodies.
IL-5 activates and recruits eosinophils, which may release a bunch of enzymes that could damage host tissue. IL-13 enhances IgE production along with IL-4 and also stimulates epithelial cells to secrete mucus.
Mast cells in the connective tissue express certain high affinity receptors called FCε receptors. These FCε receptors are specific to the FC portion of the IgE antibodies. So the antigen specific IgE antibodies bind to these high affinity surface receptors on the mast cells. The individual at this point is said to be sensitised to the antigen.
On subsequent re-exposure the antigen binds to these antibodies sitting on the mast cells cross linking them and causing the granulation of the mast cell contents. The contents in the mast cells are preformed chemical mediators already present within the cells and newly formed mediators as well as cytokines.
These are powerful mediators responsible for the clinical manifestation of Type I hypersensitivity reaction. Some of the preformed mediators contained in the mast cell granules are histamine, enzymes like chymase, tryptase and eosinophilic chemotactic factors.
Histamine causes smooth muscle contraction of the airways making it difficult to breathe.
It also causes vasodilation of blood vessels and increases their permeability. This causes an increased blood supply to the site of action and leakage of fluid through the vessels causing edema and swelling.
Enzymes like chymase and tryptase cause damage to the adjacent tissues and lead to generation of kinins and complement, leading to further inflammation.
Eosinophilic chemotactic factors recruit eosinophils to the site of allergy and are implicated in late phase reactions.
Manifestations of these mediators namely histamine and enzymes are called early phase reactions since these manifestations occur within 5 to 30 minutes of the allergen exposure and may subside within 60 minutes.
Newly synthesized mediators are usually arachidonic acid derivatives namely leukotrienes and prostaglandins.
Leukotrienes C4 and D4 are several thousand times more powerful than histamine in causing smooth muscle contraction and also causes an increased vascular permeability.
Leukotrienes B4 is a chemotactic agent for neutrophils, monocytes and eosinophils.
Prostaglandin D2 is the most abundant prostaglandin produced and causes vasodilation, increased permeability of the blood vessels and also bronchospasm.
Cytokines like IL-1 and TNF-α are pro-inflammatory cytokines that can cause further inflammation by recruiting leukocytes.
IL-4 causes further differentiation of the Th2 cells and amplifies the response.
IL-5 activates and recruits eosinophils. These mediators namely leukotrienes and cytokines are responsible for a late phase reaction which kicks in 2 to 24 hours later and does not require additional antigen exposure.
They may last for several days and are due to recruitment of more eosinophils, neutrophils, monocytes as well as CD-4 T-cells and a sustained inflammation in the environment.
Clinical Manifestations of Type-I Hypersensitivity
Some of the clinical manifestations of Type I hypersensitivity could be itching, urticaria and edema where there could be pruritic wheels surrounded by erythema.
• Allergic rhinitis and allergic asthma are other manifestations of Type I hypersensitivity.
• One of the most important complications of Type I hypersensitivity is systemic anaphylaxis, which is a widespread systemic manifestation of Type I Hypersensitivity characterized by bronchospasm resulting in difficulty in breathing, laryngeal edema for the compromising breathing, abdominal cramps as well as diarrhea.
• The patient may also develop ischemia in multiple organs due to widespread vascular permeability leading to anaphylactic shock and death.
