Objectives

After working through this module, you should be able to:

Explain the immunological mechanisms underlying type IV hypersensitivity reaction. Describe the principal causes and symptoms associated with type IV hypersensitivity reactions.

Type IV Hypersensitivity
Type IV hypersensitivity is also known as delayed

type hypersensitivity
It is different from the other 3 types of

hypersensitivity as it represents tissue damage resulting from inappropriate cell-mediated immunity reactions
Clinical conditions - tuberculosis, leprosy, contact dermatitis

Type IV hypersensitivity

Macrophage T cell ILs

Target cell Cytokines Antigen

Type IV Hypersensitivity

Initiated by the interaction of antigen with primed

T-lymphocytes and subsequently the release of soluble cytokines from the T lymphocytes which activate macrophages
Activated macrophages may differentiate into giant cells and develops into granulomantous

hypersensitivity

Type IV Hypersensitivity
Within the type IV response there are 4 different

phenomena which rarely occur separately. These are:

i. Jones-mote reaction ii. Contact hypersensitivity iii. Tuberculin reaction iv. Granulomatous reaction

Type IV Hypersensitivity
i.

Jones-mote reaction - induced by contact with allergen but is characterized by the infiltration of basophils into the inflammatory site. - the factors which cause this particular component of the reaction are unknown

Type IV Hypersensitivity

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 cells within the dermal layer of the skin

Type IV Hypersensitivity

iii. Tuberculin reaction (cont) T cells produce TNF- local vascular endothelial cells induce infiltration of neutrophils into the skin Predominant infiltrating cells mononuclear leukocytes (lymphocytes and monocytes) reaching a peak at about 48 hours

Type IV Hypersensitivity
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

Type IV Hypersensitivity
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

Type IV Hypersensitivity
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

Type IV Hypersensitivity

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, Gower

Medical 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 A

Systems Approach. McGraw-Hill. 2006.