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Objectives

After working through this module, you should be able

to:

Explain the immunological mechanisms underlyingtype IV hypersensitivity reaction.

Describe the principal causes and symptomsassociated with type IV hypersensitivity reactions.

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Type IV Hypersensitivity

Type IV hypersensitivity is also known as delayed

type hypersensitivity

It is different from the other 3 types ofhypersensitivity as it represents tissue damageresulting from inappropriate cell-mediated

immunity reactions

Clinical conditions - tuberculosis, leprosy, contact

dermatitis

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Type IV hypersensitivity

T cell

Antigen

ILs

Macrophage

Cytokines

Target cell

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Initiated by the interaction of antigen with primed

T-lymphocytes and subsequently the release ofsoluble cytokines from the T lymphocytes which

activate macrophages

Activated macrophages may differentiate into

giant cells and develops into granulomantous

hypersensitivity

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Within the type IV response there are 4 different

phenomena which rarely occur separately. Theseare:

i. Jones-mote reaction

ii. Contact hypersensitivity

iii. Tuberculin reaction

iv. Granulomatous reaction

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i. Jones-mote reaction

- induced by contact with allergen but is

characterized by the infiltration of basophilsinto the inflammatory site.

- the factors which cause this particular

component of the reaction are unknown

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iii. Tuberculin reaction

This type of hypersensitivity is the basis of the

Mantoux Test ( 72 hours- check for hard at

injection site)

The basis of tuberculin response is the re-activation of antigen-specific memory T cellswithin the dermal layer of the skin

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iii. Tuberculin reaction (cont)

T cells produce TNF- local vascularendothelial cells induce infiltration ofneutrophils into the skin

Predominant infiltrating cells mononuclearleukocytes (lymphocytes and monocytes)

reaching a peak at about 48 hours

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iii. Tuberculin reaction (cont)

Characteristic induration is a result of

combination of large number cells with oedema

Signs of reaction resolve after 5-7 days

In contrast to infection with constant source of

infection, reaction progresses to granulomatous

lesion

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iv. Granulomatous reaction

Alternative name for granulomatous

hypersensitivity is chronic inflammation

Hallmark of chronic inflammation is mononuclear

cells (monocytes, macrophages, lymphocytes)

This type of DTH has most severe consequences

due to presence of often extensive tissue damage

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iv. Granulomatous reaction (cont)

2 types of granuloma:

- foreign-body granuloma:

initiated by inert foreign bodies

- immune granuloma:

T cell-mediated reaction to immunogenic

particles

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References

Roderick Nairn and Matthew Helbert. Immunology for Medical

Students. Elsevier Mosby. 2003.

Stites DP, Terr Al and Parslow TG. Medical Immunology. 10th Edition,Appleton & Lange, Prentice-hall International Inc. 2001.

Roitt I, Brostoff J and Male D. Immunology. 6th Edition, GowerMedical Publishing, London. 2001

Cedric Mims, Hazel M. Dockrell, Richard V.Goering, Ivan Roitt, Derek

Wakelin and Mark Zuckerman. Medical Microbiology. 3rd

Edition,Elsevier Mosby. 2004.

Marjorie Kelly Cowan and Kathleen Park Talaro. Microbiology ASystems Approach. McGraw-Hill. 2006.

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