AssessmentsType IV hypersensitivity
Type IV hypersensitivity
The type IV hypersensitivity reaction is primarily a (cell/antibody) -mediated response.
USMLE® Step 1 style questions USMLE
A 27-year-old man comes to the office because of weakness in both legs for a day. Two weeks ago he had a 4-day bout of gastroenteritis, and yesterday he developed burning sensations in his toes. Examination shows facial flushing, a systolic blood pressures range of 70-160 mm Hg, profuse diaphoresis, and bilateral facial paralysis. Lumbar puncture shows a normal white cell count and elevated protein. He is treated with plasma exchange and intravenous immunoglobulin and steadily recovers over three months. Which of the following most similarly describes the type of hypersensitivity reaction that caused this patients condition?
Content Reviewers:Rishi Desai, MD, MPH
Contributors:Tanner Marshall, MS
Having a hypersensitivity means that someone’s immune system has reacted to something in such a way that it ends up damaging them, as opposed to protecting them.
There are four different types of hypersensitivities, and in the fourth type or type 4, the reactions are caused by T lymphocytes, or T cells, and so type IV is also sometimes known as T-cell-mediated hypersensitivity.
The two types of T cells that cause damage to tissues in type IV hypersensitivity are CD8+ T cells also known as killer T cells or cytotoxic T cells, as well as CD4+ T cells also known as helper T cells.
They are like silent assassins of the immune system that go after very specific targets.
So CD4+ T cells act like little army generals coordinating immune cells around them.
But both CD8+ and CD4+ cells start off as naive cells because their T cell receptor or TCR has not yet bound to their target antigen - which is that specific molecule it can bind to.
Alright so let’s play out a scenario. Let’s say someone’s skin brushes up against poison ivy, and gets the molecule urushiol all over.
That molecule’s small enough to quickly make it’s way through the epidermis to the dermis, which is where it might combine with small proteins, it then might get picked up by a langerhans cell also known as a dendritic cell, which is a type of antigen-presenting immune cell.
The dendritic cell then takes it to the nearest lymph node - the draining lymph node, where it presents the antigen on its surface using a MHC class II molecule, which is basically a serving platter for CD4+ T cells to come check out.
At this point the CD4+ or helper T cell will also express a CD28 protein which will bind to the B7 protein on the surface of the dendritic cell.
Once it binds to the TCR and the CD28 protein, the dendritic cell releases interleukin 12, a cytokine, or signaling molecule, that tells the naive CD4+ T cell to mature and differentiate into a type 1 helper T cell, or a TH1 cell - a sort of coming of age moment.
At this point, the CD4+ T cell is no longer consider naive, instead it’s an effector cell, that’s able to release the cytokine IL-2, which helps both it and other T cells in the area proliferate, as well as interferon gamma, which activates phagocytes like macrophages and creates more TH1 cells.
Those activated macrophages release proinflammatory cytokines like tumor necrosis factor, IL-1, and IL-6, which cause leakiness in the endothelial barriers and allows more immune cells into the area, all of which leads to local swelling or edema, redness, and warmth as well as systemic symptoms like a fever.
Activated macrophages will also secrete lysosomal enzymes, complement components, and reactive oxygen species into the exposed area, which damages tissue.