Topic: Hummoral and cell mediated immunity.
Question: Describe mechanism of T-cell mediated immune response in type IV hypersensitivity reaction. Explain it by giving example of tuberculin testing.
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Mechanism of type IV hypersensitivity mediated by T-cells:
1. An antigen is introduced into the skin, such as by an intradermal injection for tuberculin testing.
2. Antigen presenting cells (APCs) like Langerhans cells, dendritic cells and macrophages phagocytose the antigen at the site.
3. APCs process and digest the antigens into small peptide fragments.
4. These peptides are presented on the surface of APCs by the major histocompatibility complex (MHC) class II molecules.
5. CD4+ T helper cells in the skin recognize specific antigen peptides presented by MHC II via their T cell receptors.
6. If the individual has been previously sensitized and exposed to the antigen, memory T cells will be present for that antigen.
7. Activated memory Th1 cells release cytokines like IFN-gamma and TNF-alpha.
8. These cytokines activate more local T cells and recruit additional macrophages to the site of antigen deposition.
9. Macrophages are activated to phagocytose and kill any nearby pathogens containing the antigenic components.
10. Activated T cells and macrophages release inflammatory chemicals like cytokines and chemokines.
11. This causes vasodilation and increased blood flow and permeability at the site – leading to induration and swelling.
12. This local delayed inflammatory reaction peaks at 48-72 hours and comprises the positive type IV hypersensitivity response.
Tuberculin skin test:
– It is used to test for infection with Mycobacterium tuberculosis.
– The tuberculin extract contains proteins from M. tuberculosis.
– It is injected intradermally, usually on the forearm.
– This introduces the mycobacterial antigens into the skin and stimulates a delayed type hypersensitivity reaction mediated by memory T cells in an individual previously exposed to TB.
– After 48-72 hours, the area is checked for induration (hard swelling).
– Induration over a cutoff (10mm in most cases) indicates a positive reaction and previous TB exposure/latent TB.
– The reaction depends on cell-mediated immunity – recruitment of memory T cells to the site releases cytokines and leads to local inflammation.
– Those never exposed to TB will not have memory T cells to the antigens so will not mount an immune reaction.
– False positives can occur due to previous BCG vaccination or non-tuberculous mycobacterial infections.
– But a positive strongly suggests latent TB infection. It does not differentiate active TB disease from latent infection.
