HYPERSENSITIVIT

YAnam Zamin
Dr.
 INTRODUCTIO
N
 Hypersensitivity is the term used when an immune
response results in exaggerated or inappropriate
reactions harmful to the host.
 The term allergy is often equated with hypersensitivity
but more accurately should be limited to the IgE–
mediated reaction.
 The clinical manifestations of these reactions are typical
in a given individual and occur on contact with the
specific antigen to which the individual is
hypersensitive.
 The first contact of the individual with the antigen
sensitizes (i.e., induces the antibody), and the
subsequent contacts elicit the allergic response.
 Hypersensitivity reactions can be subdivided into four
main types. Types I, II, and III are antibody-mediated,
whereas type IV is cell- mediated.
6
 TYPE I: IMMEDIATE
(ANAPHYLACTIC)
HYPERSENSITIVITY
 An immediate hypersensitivity reaction occurs when
an antigen (allergen) binds to IgE on the surface of
mast cells with the consequent release of several
mediator.
 The process begins when an antigen induces the
formation of IgE antibody, which binds firmly by its
Fc portion to receptors on the surface of basophils
and mast cells.
 Reexposure to the same antigen results in cross-
linking of the cell-bound IgE, degranulation, and
release of pharmacologically active mediators
within minutes (immediate phase).
 Symptoms such as edema and erythema (“wheal
Immediate (anaphylactic)
hypersensitivity
 The late phase of IgE-mediated inflammation
occurs approximately 6 hours after exposure to
the antigen and is due to mediators (e.g.,
leukotrienes) that are synthesized after the cell
degranulates.
 These mediators cause an influx of inflammatory
cells, such as neutrophils and eosinophils, and
symptoms such as erythema occur.
 Note that the allergens involved in
hypersensitivity reactions are substances, such as
pollens, animal danders, foods (nuts, shellfish),
and various drugs, to which most people do not
exhibit clinical symptoms.
 However, some individuals respond to those
substances by producing large amounts of IgE
and, as a result, manifest various allergic
symptoms.
 Nonallergic individuals respond to the same antigen
by producing IgG, which does not cause the release
of mediators from mast cells and basophils.
 There is a genetic predisposition to immediate
 The clinical manifestations of type I hypersensitivity
can appear in various forms (e.g., urticaria [also
known as hives], eczema, rhinitis and conjunctivitis
[also known as hay fever], and asthma).
 The most severe form of type I hypersensitivity
is systemic anaphylaxis, in which severe
bronchoconstriction and hypotension (shock) can
be life-threatening.
 The most common causes of anaphylaxis are foods
such as peanuts and shellfish, bee venom, and
drugs such as penicillin
 Major manifestations of anaphylaxis occur when
large amounts of mediators are suddenly released
 Important
mediators
 Histamine causes vasodilation, increased capillary
permeability, and smooth muscle contraction.
Clinically, disorders such as allergic rhinitis (hay
fever), urticaria, and angioedema can occur.
 Leukotrienes cause increased vascular
permeability and smooth muscle contraction.
They are the principal mediators in the
bronchoconstriction of asthma.
 Prostaglandins and thromboxanes
 Serotonin causes capillary dilation, increased
vascular permeability, and smooth muscle
 Desensitizatio
n
 Desensitization can prevent systemic anaphylaxis.
 Acute desensitization involves the administration of
very small amounts of antigen at 15-minute
intervals. Antigen–IgE complexes form on a small
scale, and not enough mediator is released to
produce a major reaction.
 This permits the administration of a drug or foreign
protein to a hypersensitive person.
 Chronic desensitization involves the long-term
weekly administration of the antigen to
which the person is hypersensitive.
 This stimulates the production of IgA and IgG-
blocking antibodies, which can prevent
subsequent antigen from reaching IgE on mast
 Treatment &
Prevention
 Treatment of anaphylactic reactions includes
drugs to counteract the action of mediators,
maintenance of an airway, and support of
respiratory and cardiac function.
 Epinephrine, antihistamines, corticosteroids, or
cromolyn sodium, either singly or in
combination, should be given.
 There are several approaches to the treatment of
asthma. Inhaled β-adrenergic bronchodilators,
such as albuterol, are commonly used.
Corticosteroids, such as prednisone, are also
 A monoclonal anti-IgE antibody (omalizumab) is
indicated for patients with severe asthma whose
symptoms are not controlled by corticosteroids.
 For the prevention of asthma, leukotriene receptor
inhibitors, such as montelukast, and cromolyn
sodium are effective.
 The treatment of allergic rhinitis typically
involves antihistamines along with nasal
decongestants.

For allergic conjunctivitis, eye drops containing
antihistamines or vasoconstrictors are effective.
 Avoidance of the inciting allergens, such as pollens, is
helpful in prophylaxis.
 TYPE II: CYTOTOXIC
HYPERSENSITIVITY
 Cytotoxic hypersensitivity occurs when antibody
directed at antigens of the cell membrane
activates complement .
 This generates a membrane attack complex, which
damages the cell membrane.
 The antibody (IgG or IgM) attaches to the antigen
via its Fab region and acts as a bridge to
complement via its Fc region.
 As a result, there is complement-mediated lysis as
in hemolytic anemias, ABO transfusion reactions, or
Rh hemolytic disease.
 In addition to causing lysis, complement activation
Figure: Cytotoxic hypersensitivity. RBC, red
blood cell.
 Drugs (e.g., penicillins, phenacetin, quinidine)
can attach to surface proteins on red blood cells
and initiate antibody formation. Such
autoimmune antibodies (IgG) then interact with
the red blood cell surface and result in hemolysis.
 Other drugs (e.g., quinine) can attach to platelets
and induce autoantibodies that lyse the platelets,
producing thrombocytopenia and, as a
consequence, a bleeding tendency.
 TYPE III: IMMUNE COMPLEX
HYPERSENSITIVITY
 Immune complex hypersensitivity occurs when antigen–
antibody complexes induce an inflammatory response in
tissues.
 Normally, immune complexes are promptly removed by
the reticuloendothelial system, but occasionally they
persist and are deposited in tissues, resulting in several
disorders.
 In persistent microbial or viral infections, immune
complexes may be deposited in organs (e.g., the kidneys),
resulting in damage.
 In autoimmune disorders, “self” antigens may elicit
antibodies that bind to organ antigens or deposit in
organs as complexes, especially in joints (arthritis),
kidneys (nephritis), or blood vessels (vasculitis).
 Two typical type III hypersensitivity reactions are the
Arthus reaction and serum sickness.
 Arthus Reaction
 Arthus reaction is the name given to the inflammation
caused by the deposition of immune complexes at a
localized site.
 It is named for Dr. Arthus, who first described the
inflammatory response that occurs under the
following conditions.
 Antigen, antibody, and complement are deposited in
vessel walls; polymorphonuclear cell infiltration and
intravascular clumping of platelets then occur. These
reactions can lead to vascular occlusion and necrosis.
 Serum

Sickness
In contrast to the Arthus reaction, which is localized
inflammation, serum sickness is a systemic inflammatory
response to the presence of immune complexes
deposited in many areas of the body.
 It leads to the formation of immune complexes, which
may circulate or be deposited at various sites.
 Typical serum sickness results in fever, urticaria,
arthralgia, lymphadenopathy, splenomegaly, and
eosinophilia a few days to 2 weeks after injection of
the foreign serum or drug.
 Nowadays, serum sickness is caused more commonly by
drugs (e.g., penicillin).
 Immune Complex
Diseases
 Systemic Lupus Erythematosus
 Systemic lupus erythematosus is a chronic
inflammatory autoimmune disease that affects
several organs, especially the skin of the face,
the joints, and the kidneys.
 Antibodies are formed against DNA and other
components of the nucleus of cells.
 These antibodies form immune complexes that
activate complement.
 Complement activation produces C5a, which
attracts neutrophils that release enzymes,
 TYPE IV: DELAYED (CELL-MEDIATED)
HYPERSENSITIVITY
 Delayed hypersensitivity is a function of T
lymphocytes, not antibody.
 The response is “delayed” (i.e., it starts hours
[or days] after contact with the antigen and
often lasts for days).
 In certain contact hypersensitivities, such as
poison oak, the pruritic, vesicular skin rash is
caused by CD8-positive cytotoxic T cells that
attack skin cells that display the plant oil as a
foreign antigen.
 In the tuberculin skin test, the indurated skin rash
FIGURE: Delayed (cell-
mediated)
hypersensitivity
 Clinically Important
Delayed Hypersensitivity
Reactions
 Contact Hypersensitivity

 This manifestation of cell-mediated hypersensitivity occurs after

sensitization with simple chemicals (e.g., nickel, formaldehyde),
plant materials (e.g., poison ivy, poison oak), topically applied
drugs (e.g., sulfonamides, neomycin), some cosmetics, soaps, and
other substances. Neomycin is a very common cause.
 In all cases, the small molecules acting as haptens enter the
skin, attach to body proteins, and become complete antigens.
 Cell-mediated hypersensitivity is induced, particularly in the
skin.
 Upon a later skin contact with the offending agent, the
sensitized person develops contact dermatitis characterized by
erythema, itching, vesicles, eczema, or necrosis of skin within
12 to 48 hours caused by the attack of cytotoxic T cells.
 Drug
allergy
 A drug allergy is an allergy to a drug, most
commonly a medication.
 Drugs often contain many different
substances, including dyes, which could
cause allergic reactions.
 This can cause an allergic reaction on the first
administration of a drug. For example, a
person who developed an allergy to a red dye
will be allergic to any new drug which contains
that red dye.
 When a medication causes an allergic reaction, it
 Mechanis
m
 Drug allergies are attributed to "drug
hypersensitivity," initiated by exposure to a
drug at a dose normally tolerated by non-
hypersensitive persons.
 There are two mechanisms for a drug allergy
to occur:
 IgE or non-IgE mediated.
 In IgE-mediated reactions, also know as
Immunoglobulin E mediated reactions, drug
allergens bind to IgE antibodies, which are
attached to mast cells and basophils, resulting in
 Drug
Hypersensitivity
 Drugs, particularly antimicrobial agents such as
penicillin, are now among the most common
causes of hypersensitivity reactions.
 Usually it is not the intact drug that
induces antibody formation.
 Rather, a metabolic product of the drug, which
acts as a hapten and binds to a body protein,
does so.
 The resulting antibody can react with the hapten
or the intact drug to give rise to type I
hypersensitivity.
 When reexposed to the drug, the person may
exhibit a drug rash, fever, or local or systemic
 In non –IgE-mediated drug allergy, the
mechanisms include cytotoxic/cytolytic reactions
involving the interaction of IgG or IgM
antibodies and complement with a drug
allergen associated with cell membranes (e.g.,
immune hemolytic anemia, thrombocytopenia),
drug immune complex reactions and T-cell–
mediated reactions.
 Drug allergy, occurs in 1% to 2% of all
admissions and 3% to 5% of hospitalized
patients, respectively but the true incidence
 Symptom
s
 Identifying a drug allergy can sometimes be the
hardest part. Sometimes drug allergies are confused
with Nonallergic drug reactions because they both
cause somewhat similar reactions.
 Symptoms of a drug allergy can include, but are not
limited to, the following list.
 Hives
 Itching
 Rash
 Fever
 Facial swelling
 Shortness of breath
 Anaphylaxis, a life threatening drug reaction
(produces most of these symptoms as well as low
DRUG
S
 Antibiotics
🞑 Penicillin
🞑 Sulfa drugs
🞑 Tetracycline
 Analgesics
🞑 Codeine
🞑 Non-steroidal anti-inflammatory drugs
(NSAIDs)
 Antiseizure
🞑 Phenytoin
🞑 Carbamazepine