Delayed hyper sensitivities

Type IV or Delayed Hypersensitivity can be illustrated by considering the following experiment:

1. First, a guinea pig is injected with a sub-lethal dose of Mycobacterium tuberculosis (MT). Following recovery of the animal, injection of a lethal dose of MT under the skin produces only erythema (redness) and induration (hard spot) at the site of injection 1-2 days later.
2. Instead of reinjecting the immunized guinea pig, serum is transfered from this pig to a "naive" (unimmunized) pig. When this second guinea pig is now injected with MT, it dies of the infection.
3. If immune cells (T-cells and macrophages instead of serum) are transfered from the immunized pig to a second pig, the result is very different; injection of the second pig with MT causes only erythema and induration at the site of injection 1-2 days later.
4. In a separate experiment, if the immunized guinea pig is injected with a lethal dose of Listeria monocytogenes (LM) instead of MT, it dies of the infection. However, if the pig is simultaneously injected with both LM and MT, it survives.

• The reaction elicited by antigen occurs relatively slowly (hence the name "delayed hypersensitivity").
• The hypersensitivity is mediated via T-cells and macrophages.
• The hypersensitivity illustrates both antigen-specific (T-cell) and antigen non-specific (macrophage) characteristics.

1. Initial introduction of antigen produces a cell-mediated response. Mycobacterium tuberculosis is an intracellular pathogen and recovery requires induction of specific T-cell clones with subsequent activation of macrophages.
2. Memory T-cells respond upon secondary injection of the specific (i.e. MT) antigen, but not the non-specific (i.e. LM) antigen.
3. Induction of the memory T-cells causes activation of macrophages and destruction of both specific (MT) and non-specific (LM) microorganisms.