Lecture 24 - Hypersensitivity Type Iv

HYPERSENSITIVITY TYPE IV

•CMI (TDTH) is important for defense against parasites & intracellular pathogens •Sensitization phase: Ag

CD4+Th1 cell (TDTH)

memory cells

Effector phase: re-exposure to the same antigen activated Th1 cells various cytokines e.g. IL-2, IFN-γ, TNF-β attract & activate T cells, MQ & neutrophils produce various inflammatory mediators & cytokines non-specific tissue damage

Three types of DTH •Contact Hypersensitivity •Granulomatous- type hypersensitivity •Tuberculin- type hypersensitivity

Contact Hypersensitivity Caused by haptens, e.g. nickel, chemicals in rubber, cosmetics, hair dyes, etc.

Sensitization phase Haptens penetrate epidermis Hapten conjugate to body proteins Complex internalized by langerhans cells (skin APC) APC migrate to regional lymph nodes APC present Ag to CD4+ cells (TDTH)

Effector phase: Upon 2nd exposure, skin becomes infiltrated with activated TDTH (CD4+Th1), few CD8+, MQ, cytokines released (IL-2, IFN-γ, TNF). Eczematous reaction is seen locally in 48-72 hrs (swelling & erythema)

Granulomatous-Type Hypersensitivity Caused by T-cell mediated pathology, chronic inflammation Two Types: • Epitheloid cell granuloma 2. Foreign-body (or Non-immunological) granuloma

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Epitheloid cell granuloma

 This is a severe clinical form of type IV reaction  Caused by T cell-mediated immunity to persistent intracellular pathogens  MQ fail to eliminate the pathogens  Persistent microbial infections cause chronic Ag stimulus e.g. M. tuberculosis, M. leprae, sarcoidosis, some parasitic & fungal infections

Granulomas made up of: 4. A core : chronically infected MQ, epitheloid cells & giant cells 5. MQ are surrounded by activated lymphocytes 6. Collagen fibers (deposited by proliferating fibroblasts) 7. Necrosis can be seen in centre

2. Foreign-body (or Non-immunological) granuloma Caused by inability of MQ to digest particulate agents (e.g. Talc, silica), these then persist inside MQ No lymphocytes are seen in these granulomas

Tuberculin-Type Hypersensitivity BCG-vaccinated subject

A patient suspected to have Tuberculosis

injected into skin with tuberculin (Ag preparation of M. tuberculosis)

Develops swelling & erythema seen locally at site of injection in 48-72 hrs

Tuberculin-Type Hypersensitivity • Acute inflammation following injection of Ag preparation. • Site is infiltrated with CD4+Th1 cells (TDTH), few CD8+ cells, MQ (cytokine release) • Similar result seen when lepromin is injected into skin of leprosy patients

Applications of tuberculin skin test:

3. Diagnostic purposes: It is used to test patients, e.g. Tuberculin skin test, lepromin skin test

2. It is used to test the responsiveness (sensitization) of BCG-vaccinated individuals

Tests for Type IV hypersensitivity 1. Skin tests 2. Lymphocyte transformation test (LTT), peripheral blood lymphocytes are stimulated with specific antigens. Proliferation of specific lymphocytes is measured by radioactive thymidine