And then the final type of hypersensitivity, Type IV
hypersensitivity - delayed type (T-cell mediated).
Some examples here of type IV hypersensitivity reactions -
the tuberculin reaction, contact dermatitis, Hashimoto’s
thyroiditis, multiple sclerosis, type I diabetes,
Guillain-Barre syndrome, celiac disease and Crohn’s disease.
Here we have a cytokine-mediated inflammation
causing tissue injury and cell death.
Antigen presenting cells in the
tissues activate CD4+ T-cells.
This causes them to release cytokines.
And these cytokines can be involved in
the activation of cytotoxic CD8+ T-cells.
And this can result in
inflammation and tissue injury.
T-cell mediated cytotoxicity by
the CD8+ cytotoxic T-lymphocytes
can kill our own cells, and again tissue injury is the result.
The T-cell activation that occurs in type IV
hypersensitivity stimulates both macrophages and fibroblasts.
Dendritic cells can release the
cytokine interleukin-12 which is
involved in the activation of the Th1 subset of helper T-cells.
These helper T-cells characteristically produce interleukin-2,
which leads to the generation of more Th1 cells.
Gamma interferon, another characteristic
cytokine of Th1 cells can activate macrophages.
In the presence of a persistent stimulus, for example
a Mycobacterial infection or an infection with
Schistosoma, these macrophages are continually activated
and they can end up increasing largely in size.
And sometimes they fuse together to
form what are called giant cells.
And the Th1 cells can also activate fibroblasts
leading to angiogenesis and fibrosis.
One of the characteristic features of type IV hypersensitivity
is the generation of structures that are called granuloma.
This results from the activation
of Th1 cells, and the production of
pro-inflammatory cytokines such as tumor
necrosis factor and interferon gamma.
The result is that monocytes are recruited
from the blood circulation into the tissues.
And there is a massive
activation of macrophages.
Some of these fuse as we’ve
already heard to form giant cells.
This structure becomes surrounded by fibroblasts
that are also Th1 lymphocytes within this structure.
And this structure can end
up damaging the local tissue.