Type Iv Hypersensitivity

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 

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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: CellMediated (Delayed) Hypersensiti vity

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In a previously exposed individual to Mycobacterium tuberculosis:

injection of small amt of tuberculin → little immediate reaction → (24-72 hrs) indurations and redness develop

Tuberculin Skin Test Type IV: CellMediated (Delayed) Hypersensiti vity

Mononuclear cells accumulate in subcutaneous tissue 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 have internal controls (similar to placing a Candida skin test for the PPD).

Detect interferon- γ generation by the patient’s T cells in response to specific M. tuberculosis antigens (ESAT-6 and CFP-10). ü T-SPOT.TB ü QuantiFERON-TB Gold (FDA)

Interferon-γ Release Assays (IGRAs) Theoretic al and Practical Advantag es As sensitive as TST for active tuberculo sis

Logistical convenience Lack of cross reaction with BCG vaccination & nontuberculous mycobacteria. Absence of boosting ( ↑ rxn to the TST with serial testing) Avoidance of unreliable & subjective measurements

Interferon-γ Release Assays (IGRAs) QuantiFERON-TB Gold 

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Cellestis Ltd., Carnegie, Australia

Whole blood enzyme-linked immunosorbent assay (ELISA) for measurement of IFN- γ

T-SPOT.TB 

Oxford Immunotec, Oxford , UK

 Enzyme-linked immunospot (ELISpot) assay  May work best when used in combination with a PPD to increase sensitivity.  Lower rate of indeterminate results & higher degree of diagnostic sensitivity

Pharmacologic Treatment Contact Dermatitis 

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Varies depending on the severity of the disease Avoid offending antigen Corticosteroids (over the counter, prescription, injectable and

Tuberculin Skin Test 

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Rarely needed (response is short lived and self limited) Topical corticosteroids Axillary lymphadenopathy and fever: aspirin

Pharmacologic Treatment Corticosteroids 

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Have antiinflammatory properties and cause profound and varied metabolic effects Modify the body's immune response

Corticosteroids 

Triamcinolone: Decreases inflammation by suppressing migration of PMN leukocytes and reversing capillary permeability

Pharmacologic Treatment Corticosteroids 

Mometasone: May depress formation, release, and activity of endogenous chemical mediators of inflammation.

Corticosteroids 

Prednisone: May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity

Pharmacologic Treatment 

Cimetidine  H2

receptor blocker, acts as a reverse antagonist and may augment cell-mediated immunity

COMPARISON OF DIFFERENT TYPES OF HYPERSENSITIVITY