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Done by : Ala’a Abdullah
Supervised by : Dr. Hassan Abu-al Ragheb
Hypersensitivity

Hypersensitivity
• Typically, it is an excessive response to a harmless antigen that
results in injury to the tissue, disease, or even death.
• Over reaction of immune system to a harmless antigen that results
in tissue injury. It occurs when an already sensitized individual is
re-exposed to the same foreign substance.

Hypersensitivity reactions
 Type I: cell-bound antibody reacts with antigen to release physiologically
active substances.
 Type II: are those in which free antibody reacts with antigen associated with
cell surfaces.
 Type III: antibody reacts with soluble antigen to form complexes that
precipitate in the tissues.
 Type IV: sensitized T cells rather than antibody are responsible for the
symptoms that develop.
 I-III are Ig mediated and they are referred to as immediate hypersensitivity.
 IV use cell mediators and it is referred to as delayed hypersensitivity.

Type I Hypersensitivity
• The distinguishing feature of type I hypersensitivity is the short time lag,
usually seconds to minutes, between exposure to antigen and the onset of
clinical symptoms.
• The key reactant present in type I, or immediate sensitivity reactions, is IgE.
Antigens that trigger formation of IgE are called atopic antigens, or allergens.
• Atopy refers to an inherited tendency to respond to naturally occurring inhaled
and ingested allergens with continued production of IgE.
• Carl Wilhelm Prausnitz and Heinz Küstner were the first researchers to show
that a serum factor was responsible for type I reactions. Serum from Küstner,
who was allergic to fish, was injected into Prausnitz. A later exposure to fish
antigen at the same site resulted in an allergic skin reaction.

passive cutaneous anaphylaxis
It occurs when serum is transferred from an allergic
individual to a nonallergic individual, and then the
second individual is challenged with specific antigen.

• The regulation of IgE production is a function of a subset of T cells called type
2 helper cells (Th2).
• Th2 cells respond instead and produce interleukin-3 (IL-3), interleukin-4 (IL-
4), interleukin-5 (IL-5), interleukin-9 (IL-9), and interleukin-13 (IL-13).
• IL-4 and IL-13 are responsible for the final differentiation that occurs in B
cells.
• IL-5 and IL-9 are involved in the development of eosinophils.
• IL-4 and IL-9 promote development of mast cells.
• IL-4, IL-9, and IL-13 all act to stimulate overproduction of mucus, a
characteristic of most allergic reactions.
Triggering of Type I Reactions by IgE

• Tendency to respond to specific allergens appears to be linked to
inheritance of certain major histocompatibility complex (MHC) genes.
• Various human leukocyte antigen (HLA) class II molecules, especially
HLA-DR2, DR4, and DR7, seem to be associated with a high response to
individual allergens.
• Individuals who are prone to allergies exhibit certain variations in the
gene found on chromosome 11q that codes for receptors for IgE found on
several types of cells.
Triggering of Type I Reactions by IgE

Role of Mast Cells and Basophils
• Mast cells are the principle effector cells of immediate hypersensitivity.
• These cells contain numerous cytoplasmic granules that are enclosed by a
bilayered membrane.
• Histamine, which comprises approximately 10 percent of the total weight of
granular constituents, is found in 10 times greater supply per cell than in
basophils.
• Mast cells release a variety of cytokines and other mediators that enhance the
allergic response.
• Basophils represent approximately 1 percent of the white blood cells in
peripheral blood. They have a half-life of about 3 days. They contain histamine-
rich granules and high-affinity receptors for IgE, just as in mast cells.

Mediators Released from Granules
Preformed mediators
Newly synthesized mediators

Preformed Mediators
• These preformed or primary mediators include histamine,
heparin, eosinophil chemotactic factor of anaphylaxis (ECF-
A), neutrophil chemotactic factor, and proteases.
• Release of these substances is responsible for the early phase
symptoms seen in allergic reactions, which occur within 30 to
60 minutes after exposure to the allergen.

Histamine
• It is major component of mast cell granules, is appear within 30 to 60 seconds
after release, are dependent on activation of four different types of receptors
found on cells in various types of tissue.
 Activation of H1 receptors
 In the skin, histamine is responsible for local erythema or redness and wheal
and flare formation. Contraction of the smooth muscle in the bronchioles may
result in airflow obstruction. Increased vascular permeability may cause
hypotension or shock.

Eosinophil chemotactic factor of anaphylaxis
(ECF-A)
• is another preformed factor released from granules. This attracts eosinophils
to the area and induces expression of eosinophil receptors for C3b.
• Eosinophils have granules that contain major basic protein, eosinophil
cationic protein, eosinophil peroxidase, eosinophil derived neurotoxins,
histaminases, and phospholipase D. All of these products are toxic to
bronchial epithelial cells and to helminth parasites. Killing of parasites is
thought to be the reason that IgE production evolved.
• One of the proteolytic enzymes released is tryptase, Which induces
prolonged smooth muscle contraction and increases vascular permeability
and secretory activity. Complement split products are also released when C3
is converted to C3a and C3b.

Newly Synthesized Mediators
• mast cells and basophils are triggered to synthesize certain other
reactants from the breakdown of phospholipids in the cell
membrane. These products are responsible for a late phase allergic
reaction seen within 6 to 8 hours after exposure to antigen.
• Newly formed mediators include platelet activating factor
(PAF); prostaglandin (PG) D2; leukotrienes (LT) B4, C4, D4,
and E4; and cytokines.

Prostaglandins & leukotrienes
• PGD2 is the major product of mast cell. it mimics the effects of histamine,
causing bronchial constriction and vasodilation It is much more potent than
histamine, but it is released in smaller quantities.
• Leukotrienes, are also responsible for late-phase symptoms of immediate
sensitivity.
• Leukotrienes C4, D4, and E4 were originally collectively named the slow
reacting substances of anaphylaxis (SRS-A).
• LTC4 and LTD4 are 1000 times more potent than histamine in causing
increased vascular permeability, bronchoconstriction, and increased mucous
secretion in small airways.

PAF & Cytokines
• Platelet activating factor (PAF) is a phospholipid released by monocytes,
macrophages, neutrophils, eosinophils, mast cells, and basophils.
• The effects of PAF include platelet aggregation, chemotaxis of eosinophils and
neutrophils, increased vascular permeability, and contraction of smooth muscle
in the lungs and intestines.
• Cytokines released from mast cells include IL-1, IL-3, IL-4, IL-5, IL-6, IL-9,
IL-13, IL-14, IL-16, GM-CSF, and TNF alpha.
• These cytokines alter the local microenvironment, leading to an increase in
inflammatory cells such as neutrophils, eosinophils, and macrophages.

Clinical Manifestations of Immediate
Hypersensitivity
• The clinical manifestations caused by release of both preformed and newly
synthesized mediators from mast cells and basophils vary from a localized skin
reaction to a systemic response known as anaphylaxis.
• Anaphylaxis is the most severe type of allergic response, because it is an acute
reaction that simultaneously involves multiple organs.
• Anaphylactic reactions are typically triggered by glycoproteins or large
polypeptides. Smaller molecules, such as penicillin, are haptens that may
become immunogenic by combining with host cells or proteins.

Typical agents that induce anaphylaxis include:
• venom from bees.
• Wasps.
• Hornets.
• drugs such as penicillin.
• foods such as shellfish, peanuts, or dairy products.
• Latex sensitivity is now a significant cause of anaphylaxis among health-
care workers and in patients who have had multiple surgery procedures.
Clinical Manifestations of Immediate
Hypersensitivity

Clinical signs of anaphylaxis
• It is begin within minutes after antigenic challenge and may include edema, vascular
congestion, skin manifestations such as urticaria (hives) and angioedema, diarrhea
or vomiting, and intractable shock because of the effect on blood vessels and smooth
muscle of the circulatory system.
• The severity of the reaction depends on the number of previous exposures to the antigen
with consequent buildup of IgE on mast cells and basophils.
• Massive release of reactants, especially histamine, from the granules is responsible for
the symptoms. Death may result from suffocation due to upper-airway edema and
congestion, irreversible shock, or a combination of these symptoms.
• Rhinitis is the most common form of atopy, or allergy. It affects about 15 to 20 percent
of children in developed Immune Disorders countries. Symptoms include paroxysmal
sneezing; runny nose; nasal congestion; and itching of the nose and eyes.

Asthma
• is derived from the Greek word for “panting” or “breathlessness.” It can be
defined clinically as recurrent airflow obstruction that leads to intermittent
sneezing, breathlessness, and occasionally, a cough with sputum production.
• Particles no larger than 2 to 4 micro meter in diameter such as pollen, dust, or
fumes, may reach the lower respiratory tract to cause asthma.

Food allergies
• are another example of type I immediate hypersensitivity reactions.
• Some of the most common food allergies involve cow’s milk, peanuts, and
eggs. Symptoms limited to the gastrointestinal tract include cramping, vomiting,
and diarrhea, while spread of antigen through the bloodstream may cause hives
and angioedema on the skin, as well as asthma or rhinitis.
• Eczema, an itchy red skin rash, may be caused by food allergens or exposure to
house dust mites.

Treatment of Immediate Hypersensitivity
• Avoidance of known allergens is the first line of defense.
• Drugs used to treat immediate hypersensitivity vary with the severity of the
reaction.
• Immunotherapy or hyposensitization. Very small quantities of sensitizing
antigen are injected into the patient with the idea of building up IgG antibodies.
Individuals with moderate to severe symptoms are given weekly doses of
antigen that gradually increases in strength. The blocking antibodies formed
circulate in the blood and combine with antigen before it can reach IgE-coated
cells.
• A new approach involves use of an anti-IgE monoclonal antibody.

Testing for Immediate Hypersensitivity
1. In Vivo Skin Tests:
 Cutaneous & intradermal tests
2. In Vitro Tests:
 Total IgE Antigen & Specific IgE Testing
3. Microarray test

In Vivo Skin Tests
• Cutaneous and intradermal tests are the two skin tests most
often used.
• Skin testing is relatively simple and inexpensive, and it lends
itself to screening for a number of allergens.
• antihistamines must be stopped 24 to 72 hours before testing,
and there is the danger that a systemic reaction can be triggered.
• In addition, skin testing is not recommended for children under
3 years of age.

prick tests
• A small drop of material is injected into the skin at a single
point Controls should always be included:
 Negative control: saline
 Positive control: histamine
• After 15 minutes, the spot is examined a positive reaction is
formation of a wheal that is 3 mm greater in diameter than the
negative control.

Intradermal tests
• Intradermal tests use a greater amount of antigen and are more
sensitive than cutaneous testing.
• It is performed only if prick tests are negative and allergy is
still suspected.
• Tourniquet can be applied on an extremity to stop an unexpected
systemic reaction.

• A 1 mL tuberculin syringe is used to administer 0.01 to 0.05 mL of test solution
between layers of the skin.
• The test allergen is diluted 100 to 1000 times more than the solution used for
cutaneous testing.
• After 15 to 20 minutes, the site is inspected for erythema and wheal formation.
• A wheal 3 mm greater than the negative control is considered a positive test.
Intradermal tests

In Vitro Tests
• Involves measurement of:
1. Total IgE
2. Antigen-specific IgE
• These are less sensitive than skin testing put usually are less
traumatic to the patient.

Total IgE
• The first test developed for the measurement of total IgE was the competitive
radioimmunosorbent test (RIST).
• The RIST used radio labeled IgE to compete with patient IgE for binding sites
on a solid phase coated with anti-IgE.
• It has been replaced by noncompetitive solid-phase immunoassays due to the
expense and difficulty of working with radioactivity.

• It serves as a screening test to determine if more specific allergy testing is indicated.
• It is also important in diagnosis of parasitic infections; bronchopulmonary
aspergillosis; and hyper-IgE syndrome, a condition in which excessive amounts of IgE
are produced.
• Total IgE values are reported in kilo international units (IU) per liter.
• IgE concentration varies with the individual’s age, sex, smoking history and his or her
family history of allergy.
• In infants, normal serum levels of IgE are less than 2 k IU/L; increases up to 10 kIU/L
are indicative of allergic disease.
• A cutoff point of 100 IU, for adults.
Total IgE

Antigen-specific IgE
• The method that used to be done was radioallergosorbent test (RAST).
• Newer testing methods involve the use of enzyme or fluorescent labels
rather than radioactivity.
• The sensitivity of the new test approaches that of skin testing and it is safer
to perform.

• Because of this test IgE can now be measured quantitatively, and concentrations
as low as 0.35 KIU/L can be detected.
• A negative test may be used to confirm the absence of a specific atopic disease,
and this has a higher negative predictive value than total IgE testing.
• However, in a positive test, the quantity of antibody measured does not
necessarily correlate with the severity of disease.
• It is very useful to determine common food allergies and sensitivity to the
venom of stinging insects, it is more difficult to determine inhalant
allergies.
Antigen-specific IgE

 Comparison of RIST and RAST. RIST measures total IgE by capturing the antibody with
solidphase anti-IgE. A second anti-IgE immunoglobulin with an enzyme label is used to produce a
visible reaction. RAST measures antigen-specific IgE by using solid-phase antigen to capture
patient antibody. Then a second antibody, enzyme-labeled anti-IgE immunoglobulin, is added.
This combines with any bound IgE to produce a visible reaction in the presence of substrate.

Microarray testing
• It allows for multiallergen diagnosis with a low sample volume and a high
throughput capacity.
• Microarrays can be attached to a standard microscope slide, using only a few
picograms of each allergen to be tested.
• At least 5000 allergens can be tested for at once, using a minimal amount of
serum.
• Patient serum with possible IgE is allowed to react with the microarray of
allergens, and then an anti-IgE with a fluorescent tag is added, The presence of
color indicates a positive test for that allergen.

• The reactants responsible for type II hypersensitivity, or cytotoxic
hypersensitivity, are IgG and IgM.
• They are triggered by antigens found on cell surfaces. These antigens may be
altered self-antigens or heteroantigens.
• Antibody coats cellular surfaces and promotes phagocytosis by both
opsonization and activation of the complement cascade.
• Macrophages, neutrophils, and eosinophils have FC receptors that bind to the
FC region of antibody on target cells, thus enhancing phagocytosis.
• Natural killer (NK) cells also have FC receptors, and if these link to cellular
antigens, cytotoxicity results.
Type II Hypersensitivity

Transfusion Reactions
• Transfusion reactions are examples of cellular destruction that result from
antibody combining with heteroantigens.
• Major groups involved in transfusion reactions include the ABO, Rh, Kell,
Duffy, and Kidd systems.
• Certain antibodies are produced naturally with no prior exposure to red blood
cells, while other antibodies are produced only after contact with cells
carrying that antigen.
• Acute hemolytic transfusion reactions may occur within minutes or hours
after receipt of incompatible blood.
• Reactions that begin immediately are most often associated with ABO blood
group incompatibilities, and antibodies are of the IgM class.

• If a patient is given blood for which antibodies are already present, a transfusion
reaction occurs. This can range from acute massive intravascular hemolysis to an
undetected decrease in red blood cell survival.
• Delayed hemolytic reactions occur within the first 2 weeks following a
transfusion and are caused by a secondary response to the antigen to which the
patient has previously been exposed.
• The type of antibody responsible is IgG, which was initially present in such low
titer that it was not detectable with an antibody screen.
• Antigens most involved in delayed reactions include those in the Rh, Kell,
Duffy, and Kidd blood groups.
• Rh, Kell, and Duffy antigens may also be involved in immediate transfusion
reactions.
Transfusion Reactions

Hemolytic Disease of the Newborn
• Hemolytic disease of the newborn (HDN) appears in infants whose mothers have been
exposed to blood-group antigens on the baby’s cells that differ from their own. The
mother makes IgG antibodies in response, and these cross the placenta to destroy fetal
red cells.
• Severe HDN is called erythroblastosis fetalis.
• The most common antigen involved in severe reactions is the D antigen, a member of the
Rh blood group.
• HDN due to ABO incompatibility is actually more common, but the disease is milder
because the majority of antibodies formed are IgM, which cannot cross the placenta.
• Other antibodies associated with HDN include anti-c, anti-C, anti-E, anti-e, and less
commonly those associated with the Kell, Duffy, and Kidd blood groups.

• Exposure usually occurs during the birth process, where fetal cells leak into the mother’s
circulation. Typically the first child is unaffected, but the second and later children have
an increased risk of the disease.
• Depending on the degree of antibody production in the mother, the fetus may be
aborted, stillborn, or born with evidence of hemolytic disease as indicated by
jaundice.
• Bilirubin levels above 20 mg/dL are associated with deposition in tissue such as the
brain and result in a condition known as kernicterus. Treatment for severe HDN involves
an exchange transfusion to replace antibody-coated red cells.
• To prevent the consequences of HDN, all women should be screened at the onset of
pregnancy.
• In current practice, anti-D immune globulin, called Rhogam, is administered
prophylactically at 28 weeks of gestation and within 72 hours following delivery.
Hemolytic Disease of the Newborn

Autoimmune Hemolytic Anemia
• Autoimmune hemolytic anemia is an example of a type II hypersensitivity
reaction directed against self-antigens, because individuals with this disease
form antibodies to their own red blood cells.
• Such antibodies can be categorized into two groups: warm reactive antibodies,
which react at 37°C, and cold reactive antibodies, which react only below 30°C.
• Warm autoimmune hemolytic anemia, accounting for more than 70 percent of
autoimmune anemias, is characterized by formation of IgG antibody, which
reacts most strongly at 37°C. Some of these antibodies may be primary with no
other disease association, or they may be secondary to another disease process.

• Associated diseases may include some of the following: viral or respiratory infections,
such as infectious mononucleosis, cytomegalovirus, or chronic active hepatitis, or
immunoproliferative diseases such as chronic lymphocytic leukemia and
lymphomas.
• In addition, certain drugs can be adsorbed onto red blood cells and are capable of
stimulating antibody production. examples include penicillins, cephalosporins,
rifampin, sulfonamides, and methyldopa.
• Often, however, the underlying cause of antibody production is unknown, so this is
referred to as idiopathic autoimmune hemolytic anemia.
• Hemolysis is primarily extravascular, because IgG is not as efficient as IgM in activating
complement, but intravascular hemolysis can also occur if complement does become
activated.
• Patients with warm autoimmune hemolytic anemia are usually treated with
corticosteroids or splenectomy in more serious cases.

• Cold autoagglutinins, a less frequent cause of immune hemolytic anemias.
• These are thought to be triggered by antigens on microorganisms, because antibodies have
been known to occur following Mycoplasma pneumonia and infectious mononucleosis.
• Cold autoagglutinins have also been seen in such diseases as chronic lymphocytic
leukemia, non- Hodgkin’s lymphoma, myelodysplastic syndrome, or systemic lupus
erythematosus.
• These cold-reacting antibodies belong to the IgM class, and most are specific for the Ii
blood groups on red cells. Reactions are seen only if the individual is exposed to the cold
and the temperature in the peripheral circulation falls below 30°C.
• Although complement activation begins in the cold, it can proceed at body temperature. If
the entire complement sequence is activated, intravascular hemolysis may occur.
• A simple treatment is to keep the patient warm, especially the hands and feet, to prevent
complement activation.

Type II Reactions Involving Tissue Antigens
• Some type II reactions involve destruction of tissues because of combination with
antibody. Organ-specific autoimmune diseases in which antibody is directed against a
particular tissue are in this category. Goodpasture’s syndrome is an example of such a
disease.
• The antibody produced during the course of this disease reacts with basement membrane
protein. Usually the glomeruli in the kidney and pulmonary alveolar membranes are
affected. Antibody binds to glomerular and alveolar capillaries, Triggering the
complement cascade, which provokes inflammation.
• An evenly bound linear deposition of IgG in glomerular basement membrane, as detected
by fluorescent-labeled anti-IgG, is indicative of Goodpasture’s syndrome.
• Treatment usually involves the use of corticosteroids or other drugs to suppress the
immune response.
• Other examples of reactions to tissue antigens include some of the organ-specific
autoimmune diseases such as Hashimoto’s disease, myasthenia gravis, and insulin-
dependent diabetes mellitus.

Testing for Type II Hypersensitivity
• Direct antiglobulin testing (DAT) is performed to detect
transfusion reactions, hemolytic disease of the newborn, and
autoimmune hemolytic anemia.
• The indirect Coombs’ test is used in the crossmatching of blood
to prevent a transfusion reaction. It is used either to determine the
presence of a particular antibody in a patient or to type patient red
blood cells for specific blood group antigens.

• Type III hypersensitivity reactions are similar to type II reactions in that IgG or IgM is
involved and destruction is complement mediated.
• Soluble antigen combines with antibody, complexes are formed that precipitate out of
the serum.
• Normally such complexes are cleared by phagocytic cells, but if the immune system is
overwhelmed, these complexes deposit in the tissues.
• Deposition of antigen–antibody complexes is influenced by the relative concentration of
both components.
• If a large excess of antigen is present, sites on antibody molecules become filled before
cross-links can be formed.
• In antibody excess, a lattice cannot be formed because of the relative scarcity of
antigenic determinant sites.
Type III Hypersensitivity

• The small complexes that result in either of the preceding cases remain
suspended or may pass directly into the urine.
• Precipitating complexes, on the other hand, occur in mild antigen excess, and
these are the ones most likely to deposit in the tissues. Sites in which this
typically occurs include the glomerular basement membrane, vascular
endothelium, joint linings, and pulmonary alveolar membranes.
• Complement binds to these complexes in the tissues, causing the release of
mediators.
Type III Hypersensitivity

Arthus Reaction
• Antigen is injected into the skin of an individual who has
circulating antibody of that specificity.
• Immune complexes are formed and deposit on the walls of blood
vessels, activating complement.
• Complement fragments cause dilation and increased
permeability of blood vessels, edema, and accumulation of
neutrophils.

Serum Sickness
• Serum sickness is a generalized type III reaction that is seen in humans,
although not as frequently as it used to be.
• Serum sickness results from passive immunization with animal serum, usually
horse or bovine, used to treat such infections as diphtheria, tetanus, and
gangrene. Vaccines and bee stings may also trigger this type of reaction.
• In this disease, the sensitizing and the shocking dose of antigen are one and the
same, because antibodies develop while antigen is still present.
• Usually this is a benign and self-limiting disease, but previous exposure to
animal serum can cause cardiovascular collapse on reexposure.
• These symptoms have occurred with monoclonal antibody treatment.

Autoimmune Diseases
• Type III hypersensitivity reactions can be triggered by either autologous or
heterologous antigens.
• Systemic lupus erythematosus (SLE) and rheumatoid arthritis are two such
examples.
• In SLE, antibodies are directed against DNA and nucleohistones, which are
found in most cells of the body. Immune complex deposition involves multiple
organs, but the main damage occurs to the glomerular basement membrane
in the kidney.
• In rheumatoid arthritis, an antibody called rheumatoid factor is directed
against IgG. Immune complex deposition occurs in the membranes of inflamed
joints.
• Complement enhances tissue destruction in both diseases.

Testing for Type III Hypersensitivity
• In specific diseases such as SLE an rheumatoid arthritis, the presence of
antibody can be detected by agglutination reactions using antigen-coated
carrier particles, including red blood cells or latex particles, or enzym
immunoassays.
• Fluorescent staining of tissue sections has also been used to determine
deposition of immune complexes in the tissues. The staining pattern seen, and
the particular tissue affected, helps to identify th disease and determine its
severity.
• A more general method of determining immune complex diseases is by
measuring complement levels. Decreased levels of individual components or
decreased functioning of the pathway may be indicative of antigen–antibody
combination.

Type IV Hypersensitivity
• Type IV hypersensitivity differs from the other three types of hypersensitivity
in that sensitized T cells, usually a subpopulation of Th1 cells, play the major
role in it manifestations.
• Antibody and complement are not directly involved.
• There is an initial sensitization phase of 1 to 2 weeks that takes place after the
first contact with antigen.
• symptoms typically take several hours to develop and reach a peak 48 to 72
hours after exposure to antigen.
• Langerhans cells in the skin and macrophages in the tissue capture and
present antigen to T helper cells of the Th1 subclass.

• Th1 cells are activated and release cytokines, including IL-3, interferon
gamma (IFN), tumor necrosis factor-beta (TNF-), and tumor necrosis
factor alpha (TNF), that recruit macrophages and neutrophils, produce edema,
promote fibrin deposition, and generally enhance an inflammatory response.
• Cytotoxic T cells are also recruited, and they bind with antigen-coated target
cells to cause tissue destruction.
• Allergic skin reactions to bacteria, viruses, fungi, and environmental antigens
such as poison ivy typify this type of hypersensitivity.
Type IV Hypersensitivity

Contact Dermatitis
• Contact dermatitis is a form of delayed hypersensitivity.
• Reactions are usually due to low-molecular-weight compounds that touch the
skin.
• The most common causes include poison ivy, poison oak, and poison sumac.
• Other common compounds that produce allergic skin manifestations include
nickel; rubber; formaldehyde; hair dyes and fabric finishes; cosmetics;
and medications applied to the skin, such as antiseptics, and antibiotics.
• A skin eruption characterized by erythema, swelling, and the formation of
papules appears anywhere from 6 hours to several days after the exposure.

Hypersensitivity Pneumonitis
• hypersensitivity pneumonitis is mediated predominantly by sensitized T lymphocytes
that respond to inhaled allergens.
• IgG and IgM antibodies are formed, but these are thought to play only a minor part.
• This is an allergic disease of the lung parenchyma, characterized by inflammation of
the alveoli and interstitial spaces.
• The reaction is most likely due to microorganisms, especially bacterial and fungal
spores, that ndividuals are exposed to from working with moldy hay, compost, moldy
tobacco, infested flour, and moldy cheese.
• Symptoms include a dry cough, shortness of breath, fever, chills, weight loss, and
general malaise.
• Systemic corticosteroid therapy is used for treatment.

Tuberculin-Type Hypersensitivity
• Testing for exposure to tuberculosis is a classic example of a delayed hypersensitivity
reaction. This is based on the principle that soluble antigens from Mycobacterium
tuberculosis induce a reaction in people who have or have had tuberculosis.
• When challenged with antigen intradermally, previously sensitized individuals develop
an area of erythema and induration at the injection site.
• The blood vessels become lined with mononuclear cells, and the reaction reaches a peak
by 72 hours after exposure.
• The tuberculin skin test uses a Mycobacterium tuberculosis antigen prepared by making a
purified filtrate from the cell wall of the organism. This purified protein derivative
(PPD) is injected under the skin, and the reaction is read at 48 to 72 hours.
• A positive test indicates that the individual has previously been exposed to
Mycobacterium tuberculosis or a related organism, but it does not necessarily mean
there is a presently active case.

Testing for Delayed Hypersensitivity
(The patch test)
• The patch test is considered the gold standard in testing for contact
dermatitis.
• This must be done when the patient is free of symptoms or when he or she at
least has a clear test site.
• A nonabsorbent adhesive patch containing the suspected allergen is applied on
the patient’s back, and the skin is checked for a reaction over the next 48
hours.
• Final evaluation is conducted at 96 to 120 hours. All readings should be
done by a skilled evaluator.
• False negatives can result from inadequate contact with the skin.

Testing for Delayed Hypersensitivity
(Mantoux method)
• Mantoux method, is performed in much the same manner as testing for the
presence of IgE.
• Typically, 0.1 mL of the antigen is injected intradermally, using a syringe and a
fine needle.
• The test site is read at 48 and 72 hours for the presence of induration.
• An induration of 5 mm or more is considered a positive test.
• Antigens typically used for testing are Candida albicans, tetanus toxoid,
tuberculin, and fungal antigens such as trichophyton and histoplasmin.

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