TYPE IV

HYPERSENSITIVITY
Group 3 Medicine 2C
Clinical Summary
 Gigi, a 2 year old girl was brought for
consult at the Out-patient department
because of poor weight gain. She also
has a history of recurrent cough and
colds occurring at least monthly. The
physicians at the OPD suspected a
primary tuberculosis and suggested a
tuberculin skin test (purified protein
derivative or PPD). After administering
the PPD on Gigi’s right volar forearm, she
was advised to come back after 2 days to
check for the presence of induration on
Guide Questions
1. What type of hypersensitivity reaction
does tuberculin skin testing exemplify?
 The tuberculin reaction is a classic
example of a cell-mediated (delayed)
hypersensitivity.
 When a small amount of tuberculin is
injected into the epidermis of a patient
previously exposed to Mycobacterium
tuberculosis, there is little immediate
reaction; gradually, however, induration and
redness develop and reach a peak in 24–72
hours.
Guide Questions
2. Give other examples of this type of
reaction.
Contact hypersensitivity is another
example of cell-mediated
hypersensitivity.
It occurs after sensitization with simple
chemicals , plant materials, topically applied
drugs some cosmetics, soaps, and other
substances. In all cases, small molecules
enter the skin and then, acting as haptens,
attach to body proteins to serve as
complete antigen.
Cell-mediated hypersensitivity is induced,
particularly in skin. When the skin again
Guide Questions
 3. The primary cells involved in delayed
hypersensitivity reactions are monocytes
and T-cells
Cytokines
 IL 12 – produced by macrophages,
differerentiation of naïve CD4 helper
Tcells to Th1 cells, produce cytokines
 IFN gamma –key mediator, activates
macrophages, produce more Class II
molecules, secrete PDGF, secrete TNF,
IL1 and chemokines
 IL 2 – autocrine and paracrine
proliferation of tcells and CD4 and helper
tcells
Type IV hypersensitivity
Continuation…
Other DIAGNOSTIC TESTS

Other DIAGNOSTIC TESTS

•TST
•Multipuncture Tests (MPTs)
•Interferon-γ Release Assays (IGRAs)
Multipuncture Tests (MPTs)

Multipuncture Tests (MPTs)

not as accurate as TST because the
exact dose of tuberculin antigen
introduced into the skin cannot be
controlled.
• No longer used in pediatric practice.
Tuberculin Skin Test

Tuberculin Skin Test

The tuberculin skin test is performed to evaluate whether a person has been exposed to
Tuberculin Skin Test / Mantoux
Test
Tuberculin Skin Test /
Mantoux Test
The Mantoux test itself is a delayed
hypersensitivity reaction. Thus, 48-72 hours
following the intradermal administration of
purified M. tuberculosis protein derivative (PPD),
patients who have been exposed to the bacteria
develop a delayed hypersensitivity reaction
manifested by inflammation and edema in the
Tuberculin Skin Test

Type IV: Cell-  In a previously exposed

Mediated
(Delayed) individual to Mycobacterium
Hypersensiti tuberculosis:
vity

injection of small amt of

tuberculin → little immediate
reaction → (24-72 hrs)
indurations and redness
develop
Tuberculin Skin Test

Type IV: Cell- Mononuclear cells accumulate

Mediated
(Delayed) in subcutaneous tissue
Hypersensiti
vity Abundance of CD4 TH1

(+) Skin Test = individual

infected with agent +/-
presence of current disease
(-) →(+) Skin Test = recent
infection + possible current
activity.
TST Results

TST Results
≥ 5mm close contact with known/ suspected contagious people with TB; suspected
to have TB; immunosuppressive therapy / conditions
≥10mm increased risk of disseminated TB; increased exposure to TB
Limitations of TST

Limitations of TST
Interferon-γ Release Assays
(IGRAs)
Both tests Detect interferon- γ generation
have
internal by the patient’s T cells in
controls response to specific M.
(similar to
placing a tuberculosis antigens (ESAT-6
Candida
skin test
and CFP-10).
for the
PPD).
ü T-SPOT.TB
ü QuantiFERON-TB Gold (FDA)
Interferon-γ Release Assays
(IGRAs)
Theoretic Logistical convenience
al and
Practical Lack of cross reaction with
Advantag BCG vaccination &
es
nontuberculous
As
mycobacteria.
sensitive Absence of boosting ( ↑ rxn
as TST for
active to the TST with serial
tuberculo testing)
sis
Avoidance of unreliable &
subjective measurements
Interferon-γ Release Assays
(IGRAs)
QuantiFERON-TB Gold T-SPOT.TB
Oxford Immunotec, Oxford , UK
 Cellestis Ltd., Carnegie, 

Australia
 Enzyme-linked
immunospot
 Whole blood (ELISpot) assay
enzyme-linked  May work best when
used in combination
immunosorbent with a PPD to
assay (ELISA) for increase sensitivity.
measurement of  Lower rate of
indeterminate results
IFN- γ & higher degree of
diagnostic sensitivity
Pharmacologic Treatment

Contact Dermatitis Tuberculin Skin Test

 Varies depending  Rarely needed

on the severity of (response is short
the disease lived and self
 Avoid offending limited)
antigen  Topical
 Corticosteroids corticosteroids
(over the counter,  Axillary
prescription, lymphadenopathy
injectable and and fever: aspirin
Pharmacologic Treatment

Corticosteroids Corticosteroids

 Have anti-  Triamcinolone:

inflammatory Decreases
properties and inflammation by
cause profound suppressing
and varied migration of PMN
metabolic effects leukocytes and
reversing capillary
 Modify the body's
permeability
immune response
Pharmacologic Treatment

Corticosteroids Corticosteroids

 Mometasone:  Prednisone: May

May depress decrease
formation, release, inflammation by
and activity of reversing
endogenous increased capillary
chemical permeability and
mediators of suppressing PMN
inflammation. activity
Pharmacologic Treatment
 Cimetidine
 H2receptor blocker, acts as a reverse
antagonist and may augment cell-mediated
immunity
COMPARISON OF DIFFERENT TYPES OF
HYPERSENSITIVITY