ALLERGY
An allergic reaction is a manifestation of tissue injury
resulting from interaction between an antigen and an
antibody. Allergy is an inappropriate and often
harmful response of the immune system to normally
harmless substances, called allergens.
Ex. of allergens:
a. Dust
b. Pollen
c. Weeds
d. Dander
In the process of an allergic reaction, there will be a
release of chemical mediators that will produce a
range of symptoms ranging from mild to life
threatening.
In allergic reactions, the body encounters allergens
that are types of antigens, usually proteins that the
body’s defenses recognize as foreign, and a series of
events occur in an attempt to render the invaders
harmless, destroy them, and remove them from the
body.
Role of Immunoglobulins
Immunoglobulins - antibodies that are formed by
lymphocytes and plasma cells in response to an
immunogenic stimulus constitute a group of serum
proteins.
Immunoglobulins of the IgE class
• involved in allergic disorders and some
parasitic infections. IgE-producing cells are
located in the respiratory and intestinal
mucosa.
• two or more IgE molecules bind together to
an allergen and trigger mass cells (basophil).
When they trigger basophil, it then releases
chemical mediators such as histamine,
serotonin, kinins, slow reacting substances of
anaphylaxis and neutrophil factor thereby
producing an allergic reaction.
Atopy – refers to IgE mediated diseases, such as
allergic rhinitis, that have a genetic component.
B cells (B lymphocytes)
• are programmed to produce one specific
antibody.
• on encountering a specific antigen, B cells
stimulate production of plasma cells, the site
of antibody production. The result is the
outpouring of antibodies for the purpose of
destroying and removing the antigens.
• part of adaptive immunity.
T cells (T lymphocytes)
• assist the B cells.
• secrete substances that direct the flow of
cell activity, destroy target cells, and
stimulate the macrophages.
• digest antigens and assist in removing
cells and other debris.
• does not bind to free antigens.
Antigens
• acts as the trigger of immune response
• divided into 2 groups:
1. Complete Protein Antigens
➢ Refers to animal dander, pollen,
and horse serum.
➢ Stimulate a complete humoral
response.
2. Low Molecular Weight Substances
➢ such as medications, function as
haptens (incomplete antigens),
binding to tissue or serum
proteins to produce a carrier
complex that initiates an antibody
response.
➢ Haptens – molecules that are
incapable alone of causing the
production of antibodies, but it
can do so when it is fastened to a
larger antigenic molecule called a
carrier.
Mast Cell Primary Mediators
• responsible for producing chemical mediators. 1. Histamine
➢ Vasodilation, smooth muscle
• Located in the skin and mucous membranes,
contraction, increased vascular
play a major role in IgE-mediated immediate
permeability, increased secretions.
hypersensitivity.
• When mast cells are stimulated by antigens,
2. Platelet-Activating Factor
powerful chemical mediators are release,
➢ Initiates platelet aggregation and
causing a sequence of physiologic events that
leukocyte infiltration at sites of
result in symptoms of immediate
immediate hypersensitivity reactions.
hypersensitivity.
➢ Causes vasodilation,
bronchoconstriction, and increased
vascular permeability.
Chemical Mediators produced by mast cell
3. Eosinophil Chemotactic Factor of Anaphylaxis
Histamine
➢ Attracts eosinophils
• Histamine action results from stimulation of
histamine-1 (H1) and histamine-2 (H2)
4. Prostaglandins
receptors.
➢ Produce smooth muscle contraction
➢ H1 receptors – found predominantly
as well as vasodilation and increased
on bronchiolar and vascular smooth
capability permeability. They sensitize
muscle cells.
pain receptors and increase the pain
➢ H2 receptors – found on gastric
associated with inflammation.
parietal cells.
➢ Methanolic acid – a drug that act on
• Histamine’s effects peak 5-10 minutes after
the prostaglandins and for the pain.
antigen contact and include the following:
➢ Erythema and itchyness
➢ Localized edema in the form of
Secondary Mediators
wheals
1. Leukotrienes
➢ Pruritis
➢ Initiate the inflammatory response.
➢ Contraction of bronchial smooth
➢ Responsible for smooth muscle
muscle, resulting in wheezing and
contraction, bronchial constriction,
bronchospasm
mucus secretion in the airways, and
➢ Dilation of small venules and
the typical wheal-and-flare reactions
constriction of larger vessels
of the skin.
➢ Increased secretion of gastric and
➢ 100-1,000 times more potent in
mucosal cells resulting in diarrhea.
causing bronchospasm compare to
histamine.
Diphenhydramine
• Antihistamine drug that targets histamine 2. Bradykinin
receptors. ➢ cause increased permeability,
• Medication that displays an affinity for H1 vasodilation, hypotension, and
receptors. contraction of many types of smooth
muscle, such as the bronchi.
Cimetidine and Ranitidine ➢ Increased permeability of the
• Target H2 receptor to inhibit gastric secretion capillaries results in edema.
in peptic ulcer disease.
 ➢ Stimulates nerve cell fibers and
produces pain.
3. Heparin – anticoagulant
4. Serotonin – acts as a potent vasoconstrictor
and causes contraction of bronchial smooth
muscle.
HYPERSENSITIVITY
➢ An excessive aberrant immune response to
any type of stimulus (Abbas et al., 2014). It
usually does not occur with the first exposure
to an allergen. Rather, the reaction follows a
re-exposure after sensitization, or buildup of
antibodies, in a predisposed person.
Types of Hypersensitivity Reactions
1. Anaphylactic (Type 1) Hypersensitivity
➢ IgE-mediated
➢ Onset is within 1 hour
➢ The most severe hypersensitivity reaction
is anaphylaxis
➢ Standard treatment for anaphylaxis is
epinephrine
➢ Unanticipated severe allergic reaction
that is rapid in onset.
➢ Anaphylaxis is characterized by edema in
many tissues, including the larynx, and
often accompanied by hypotension,
bronchospasm, and cardiovascular
collapse in severe cases.
➢ An immediate reaction beginning within
minutes of exposure to an antigen.
➢ Primary chemical mediators are
responsible for the symptoms of type 1
hypersensitivity because of their effects
on the skin, lungs, and gastrointestinal
tract.
➢ Happens during the second time.
➢ Pathophysiology:
a. First time an allergy prone person
runs across an allergen such as
ragweed
b. He/she makes large amounts of
ragweed IgE antibody
c. Then, the IgE molecules attach
themselves to mast cells
d. The second time that person has a
brush with ragweed, the allergen
crosslinks the surface bound IgE and
activated signal from the cytoplasmic
portion of Ige
e. The IgE primed mast cells then release
granules and powerful chemical
mediators, such as histamine and
cytokines, into the environment.
f. These chemical mediators cause the
characteristics symptoms of allergy.
Clinical Manifestations of Anaphylaxis
➢ Swelling of the conjunctiva
➢ Runny rose
➢ Swelling of lips, tongue and/or throat
➢ CNS: lightheadedness, loss of consciousness,
confusion, headache, anxiety
➢ Respi: shortness of breath, wheezes or
stridor, hoarseness, pain with swallowing,
cough
➢ GI: crampy abdominal pain, diarrhea,
vomiting, loss of bladder control, pelvic pain
➢ Heart and vasculature: fast or slow heart rate
and low blood pressure
➢ Skin: hives, itchiness, flushing
2.Cytotoxic (Type 2) Hypersensitivity
➢ IgM or IgG cytotoxic
➢ Onset: hours to days
➢ Ex. hemolytic anemia
➢ Occurs when the system mistakenly identifies
a normal constituent of the body as foreign.
This reaction may be the result of a cross
reacting antibody, possibly leading to cell and
tissue damage.
➢ Example is blood transfusion reaction:
a. Donate type A blood with type A
antigens enters bloodstream of type B
recipient
b. Anti-A antibodies in plasma if type B
recipient bind to donated type AA red
blood cells
c. Bound anti-A antibodies activate
complement cascade, causing
hemolysis and release of hemoglobin.
3. Immune Complex (Type 3) Hypersensitivity
➢ Immune complex-mediated
➢ Onset: 1-3 weeks
➢ Involves immune complexes that are formed
when antigens bind to antibodies.
➢ Cleared from the circulation by phagocytic
action.
➢ If these type 3 complexes are deposited in
tissues or vascular endothelium, two factors
contribute to injury:
a. The increased amount of circulating
complexes
b. The presence of vasoactive amines
➢ As a result, there is an increase in vascular
permeability and tissue injury.
➢ Happens in patient with systemic lupus
erythematosus (SLE)
➢ Pathophysiology:
a. Antigen and B cell activated
b. Stimulates plasma cell and produce
antibodies
c. Antibodies bind with antigen forming
immune complex
d. Excess immune complex
e. Complexes get deposited in certain target
tissues on which circulation is low or
filtration of blood occurs like kidney and
synovial membrane of joints
f. Activate a complement cascade which
results in the formation of vaso-active
amines.
g. Complement cascade generates
fragments which are chemotactic to
neutrophils (neutrophil activation)]
h. Process of phagocytosis, there is a release
of degradative enzymes (lysosmal)
i. Amines altered the permeability of the
affected tissue thereby causing tissue
damage
4. Delayed-Type (Type 4) Hypersensitivity
➢ T cell-mediated
➢ Onset: days to weeks
➢ Ex. Rash Stevens-Johnson syndrome (SJS)
➢ Immune reaction in which T-cell dependent
macrophage activation and inflammation
cause tissue injury.
➢ This type of reaction to the subcutaneous
injection of antigen is often used as an assay
for cell-mediated immunity (e.g., the purified
protein derivative skin test or immunity to
Mycobacterium tuberculosis)
➢ Ex. kidney transplant
Diagnostic Findings
1. Complete Blood Count with differential
• Eosinophil level greater than 5% to
10% is considered abnormal and may
be found in patients with allergic
disorders.
2. Eosinophil Count
• Smears obtained from nasal
secretions and sputum of patients
with allergic usually reveal an increase
in eosinophils, indicating an active
allergic response.
3. Total Serum Immunoglobulin E levels
• High total serum IgE levels support
the diagnosis of allergic disease.
4. Skin Tests
• Considered to be the most accurate
confirmation of an allergy.
5. Provocative Test
• Involves the direct administration of
the suspected allergen to the
sensitive tissue such as conjunctive,
nasal, bronchial mucosa or GI tract
• Helpful in identifying clinically
significant allergens in patients who
have a large number of positive tests
6. Serum-specific IgE Test
• Automated test performed on blood
sample
• Detects free-antigen-specific IgE in
serum as opposed to antigen-specific
IgE bound to mast cells in the skin
• Includes decreased risk of systemic
reaction, stability of antigen, and lack
of dependence and skin reactivity
modified by medications