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 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
recognizing 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 may pick
these allergens swim to a nearby lymph
node 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 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 issue.
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 FCεRI
receptors. These FCεRI 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 sensitized 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 five to
thirty 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. Leukotriene 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.
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.
