Hypersentivity, Type 4
Type 4 hypersensitivity reactions are mediated by antigen-specific activated T-cells.
When the antigen enters the body, it is processed by antigen-presenting cells and presented together with the MHC II to a Th1 cell.
If the T-helper cell has already been primed to that specific antigen, it will become activated and release chemokines to recruit macrophages and cytokines such as interferon-γ to activate them.
Activated macrophages release pro-inflammatory factors, leading to local swelling, oedema, warmth, and redness. They also secrete lysosomal elements and reactive oxygen species, again leading to local tissue damage. CD8+ T cells may be involved in type 4 reactions where a foreign antigen is detected on a cell, such as in organ rejection: this is known as cell mediated cytotoxicity, and also results in recruitment and activation of macrophages.
This reaction is also known as delayed-type hypersensitivity due to its characteristic longer time period to appear following antigen exposure. The reaction takes longer than all other types because of the length of time required to recruit cells to the site of exposure – around 24 to 72 hours.
Clinical Relevance - Contact Dermatitis
Contact dermatitis can result from a wide variety of innocuous substances, such as nickel, poison ivy, or household cleaning products. Because of the delay in transporting Th1 cells to the site of infiltration, symptoms can develop several days after initial exposure to the substance, but redness, itching, swelling, and heat are all common.
Dr.khatmando [CC BY-SA (https://creativecommons.org/licenses/by-sa/4.0)]
Fig 3.0 – Image showing contact dermatitis resulting from a buprenorphine transdermal patch
Summary Table
Type Type 1 Type 2 Type 3 Type 4 Reactant IgE IgG IgG T effector cells Mechanism Mast-cell activation releases histamines and other mediators Antigens embedded in host cells cause complement activation and destruction by MAC. Antibody binds to soluble antigen, forming a circulating immune complex lodges in a vessel wall and causes a local inflammatory response. APC activates Th1/CTL. T cells activation macrophages and cause an inflammatory response. Time course Minutes Days Example Anaphylaxis Acute Transfusion Reaction Rheumatoid Arthritis, Vasculitis, Glomerulonephritis Contact Dermatitis, Mantoux tuberculin test