| Themes > Science > Life Sciences > General Biology > Immunology > The Immune System & Disease > Hypersensitivity and Chronic Inflammation > Type IV Hypersensitivity |
This is the only class of hypersensitive reactions to be triggered by antigen-specific T cells. We would now call these TH1 cells but they were originally termed TDTH after the alternative name for this reaction - delayed type hypersensitivity. . |
| The classical mechanistic
explanantion is illustrated above. Delayed type hypersensitivity results
when an antigen presenting cell, typically a tissue dendritic cell which
has picked up antigen, processed it and displayed appropriate peptide
fragments bound to class II MHC is contacted by an antigen specific TH1
cell patrolling the tissue. The resulting activation of the T cell
produces cytokines such as chemokines for macrophages, other T cells and,
to a lesser extent, neutrophils as well as TNFbeta and IFNgamma. The
consequences are a cellular infiltrate in which mononuclear cells (T cells
and macrophages) tend to predominate. It is usually maximal in 48-72
hours. The problem which this explanation faces is the rarity of antigen-specific T cells. Despite the fact that "memory T cells", unlike naive T cells, do circulate through tissues, there is some doubt that a single T cell could initiate the event. The answer to this conundrum may lie in the recent observations that at least some Type IV reactions absolutely require the presence of 'natural' IgM antibody for initiation. Due to the nature and kinetics of the reaction it is still believed that activation of memory TH1 cells is primarily responsible for propagating the reponse, but initiation may require IgM and probably also complement. One theory is that limited IgM-antigen complexes in local capilliaries may lead to a limiting, localised complement activation within the vessel activating the vascular endothelium and thus recruiting inflammatory cells including memory T cells. The classical example of delayed type hypersensitivity is in tuberculosis but this will be covered in the Lent term. A more familiar example is contact hypersensitivity which results from exposure of certain individuals to metal salts and small reactive chemicals. It is important to note that in such cases the antigen must be a complex of the hapten and a self peptide and T cells specific for Ni++ and reactive chemicals eg dinitrofluorobenzene have been isolated. |
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