Imm 17 type iv hs
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T CELL-MEDIATED HYPERSENSITIVITY(TYPE IV)
DR. HASNI MAHAYIDIN ([email protected])IMMUNOLOGY UNITPATHOLOGY DEPARTMENTFACULTY OF MEDICINE AND HEALTH SCIENCESUNIVERSITI PUTRA MALAYSIA
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RECAP•Hypersensitivity reaction:
▫Excessive / inappropriate immune response
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RECAP•Classification of hypersensitivity:
▫Coombs and Gell (1963)
TYPES IMMUNE COMPONENT
CLINICAL
I (immediate) IgE, mast cells, eosinophils
Allergic reactions
II Antibodies (IgG, IgM)
Antibody-mediated cell reactions
III Antibodies Immune complex-mediated reactions
IV T cells Cell-mediated reactions
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T cell-mediated immune response
Immunity
Innate
Adaptive
Humoral
Cell- mediate
d
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Type IV hypersensitivity•aka:
▫Delayed-type hypersensitivity (DTH)▫T cell-mediated hypersensitivity▫Cellular-mediated hypersensitivity
•T cell-mediated inflammatory response
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T cell-mediated HS•Involved antigen specific CD4+ T cells•CD4+ T cells are normal component of
adaptive immunity•Essential for control of pathogens,
particularly intracellular organisms•May also response to chemicals and self
antigens•However, if the response is excessive
damage to host
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•2-phase:▫Sensitization phase▫Effector phase
•>12hrs to develop (according to the Coombs and Gell classification)
•Three variants of DTH:▫Contact Hypersensitivity▫Tuberculin-type Hypersensitivity▫Granulomatous Hypersensitivity
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•The 3 types of DTH were originally distinguished according to the reaction they produced when the antigen was directly applied to the skin (epicutaneously) or injected intradermally.
•The degree of response is usually assessed by measuring thickening of the skin.
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Phases of DTH• Primary contact
• Sensitization (1-2 weeks) Antigen presentation by APC Occur in regional lymph nodes Priming of antigen specific CD4 cells
• Effector phase due subsequent exposure to the antigens (peaks 48-72 hrs)
Recruitment of antigen specific CD4 cells Influx of macrophages Secretion of pro-inflammatory cytokines
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•Three variants of DTH:▫Contact Hypersensitivity▫Tuberculin-type Hypersensitivity▫Granulomatous Hypersensitivity
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Contact hypersensitivity•aka contact dermatitis
Nickel watch Nickel pendant
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Nickel ear ringRubber slippers
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Rubber gloves Contact dermatitis due rubber gloves
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Contact dermatitis• Occur at the point of contact with an allergen
(usually haptens)• Hapten: a small molecule that can not elicit an
immune response on its own• Haptens bind to carrier (tissue) protein to form
neo-antigen (immunogenic)• Uptake by Langerhans’ cells stimulation of
keratinocytes & pro-inflammatory cytokines • Present to T cells at regional lymph nodes• Recruitment of effector T cells and macrophages• Dermatitis (eczema)
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Patch test
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Tuberculin hypersensitivity•Seen following tuberculin skin test (TST)
or Mantoux test•Induced by soluble antigens from a
variety of organism•Originally developed by Koch in 1890•Current technique in use was described in
1912 by Charles Mantoux, a French physician
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•Soluble antigens introduced intradermally•Characteristic skin-test reaction
(induration) that peak after 24 hours
•Skin induration is thickening of the skin due to migration of lymphocytes and macrophages into the dermis, the proliferation of cells in the dermis in response to cytokines, and the deposition of new extracellular matrix.
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Mantoux test
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•Positive reaction shows existence of antigen specific T cells (previous exposure)
Due pathogenic form of M. tuberculosis BCG vaccination
•Can be done for other infections as well
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Granulomatous hypersensitivity•Due to intracellular pathogens that resist
macrophage killing•Chronic/ continuous T cell stimulation
leads to cytokine secretion (IL-3, IFN-γ & GM-CSF)
•Recruit & activate macrophages• Failure of eradicating intracellular
pathogens induces epithelioid cell transformation
•Epithelioid cells secretes TNF-α and induce cell fusion to form giant cells
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Granuloma • Granuloma is composed
of a core of infected (and uninfected) macrophages, epithelioid cells, multi-nucleated giant cells (fusion of activated macrophages), along with peripheral accumulation of T lymphocytes, plasma cells, maybe a few neutrophils and fibroblasts with collagen; with or without central necrosis.
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•Many chronic diseases manifest granulomatous hypersensitivity
•Most are due to infectious agents▫Tuberculosis (TB) M.tuberculosis▫Leprosy M.leprae▫Schistosomiosis worm schistosomas
•In some, no infectious agents has been established▫Sarcoidosis▫Crohn’s disease
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Pulmonary tuberculosis
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Leprosy • A chronic infection by
bacteria M.leprae and M.lepromatosis
• Initially infections are without symptoms and for 5 - 20 years. Symptoms that develop include granulomas of the nerves respiratory tract, skin, and eyes.
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•This may result in a lack of ability to feel pain and thus loss of parts of extremities due to repeated injuries.
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Reference•Immunology 7th edition, David Male et al.,
Mosby Elsevier, Canada. 2006.