BP-605T BIOTECHNOLOGY UNIT- III HYPERSENSITIVITY

Type IV Hypersensitivity
Reaction
• Cell-mediated hypersensitivity reaction
• Unlike the other hypersensitivity reactions, which are mediated by antibodies (Abs), type
IV involves antigen-specific effector T cells.
• Does not occur until 24–72 hours after exposure of a sensitized individual (thus, delayed-
type hypersensitivity)
• The delay is due to the time required for T cell differentiation, cytokine and chemokine
secretion, and accumulation of leukocytes at the site.
T cell function
• Type IV hypersensitivity reactions do not involve antibodies.
• Instead, T cells are involved. Major types:
➢ T-helper (Th) cells
▪ CD4+ T cells/Th cells
▪ Regulate immune response by secreting cytokines that activate B cells,
other T cells, and phagocytes
➢ Cytotoxic T cells
▪ CD8+ T cells/Tc (cytotoxic or killer T cells)
▪ Directly kill cells or utilize cytokines in an immune response

Mechanism of Type IV (Cell Mediated) Hypersensitivity

• In type IV hypersensitivity reaction, when a sub-population of CD4 Th1 cells encounter

certain type of antigens, they produce cytokines which induce a localized inflammatory
reaction mediated by non-specific inflammatory cells most prominently marcrophages.
• The antigens involved may be either intracellular pathogens such as Mycobacterium
tuberculosis, Listeria monocytogens, Histoplasma capsulatum, Herpes Simplex virus etc. or
contact antigens such as Nickel salts, Poison ivy etc.
• The reaction is accomplished in two phases: the initial sensitization phase and the later
effector phase.
• In the sensitization phase, the primary contact with the antigen is established. During this
period, specific Th cells are sensitized and are clonally expanded.
• In the effector phase, a subsequent exposure to the same antigen induces the delayed type
hypersensitivity response.
• Cytokines such as IL-2 and interferon gamma is released inducing the further release of
other Th1 cytokines, which mediates the immune response activating macrophages and
other non-specific inflammatory cells.

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BP-605T BIOTECHNOLOGY UNIT- III HYPERSENSITIVITY

• Activated CD8+ T cells on the other hand, destroy target cells on contact, whereas activated
macrophages produce hydrolytic enzymes and on presentation with certain
intracellular pathogens, transform into multinucleated giant cells.

Mechanism of type IV hypersensitivity reaction

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BP-605T BIOTECHNOLOGY UNIT- III HYPERSENSITIVITY

Examples of Type IV (Cell Mediated) Hypersensitivity

1. The tuberculin reaction (Mantoux test): This is a ‘recall’ response to purified

mycobacterial antigens and is used as the basis of a diagnostic skin test for an immune
response to tuberculosis.
2. Granuloma formation: The inability to kill intracellular pathogens in macrophages often
results in a chronic stimulation of the pathogen specific T cells. The cytokines produced are
responsible for ‘walling off’ the macrophages containing the persistent antigens and thus the
production of granulomas.
3. Allergic contact dermatitis: Environmental chemicals, metals or topical medications
causing epidermal necrosis, inflammation, skin rash and blisters.
4. Type-1 diabetes: The killing of the pancreatic islet cells by cytotoxic T cells resulting in
insulin deficiency.

Type V Hypersensitivity (Stimulatory)

)type))Reaction

• This is an additional type that is sometimes (often in Britain) used as a distinction from
Type 2 (Modification of Type II hypersensitivity reactions)
• Instead of binding to cell surface components, the antibodies recognize and bind to the
cell surface receptors, which either prevent the intended ligand binding with the receptor
or mimic the effects of the ligand, thus impairing cell signaling.
• Some clinical examples:
Graves' disease (Long Acting Thyroid Stimulating Antibody)
Myasthenia gravis
• The use of Type 5 is rare.
• These conditions are more frequently classified as Type 2, though sometimes they are
specifically segregated into its own subcategory of Type 2.

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