Type IV hypersensitivity

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Type IV hypersensitivity


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USMLE® Step 1 questions

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Type IV hypersensitivity

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USMLE® Step 1 style questions USMLE

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A 32-year-old man presents to the clinic with a pruritic rash on his abdomen for one day. It began as a macular rash that progressed to pruritic papules. This inflammatory process is mediated by which of the following cell types?  

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Chemokines p. 106

delayed hypersensitivity p. 110

Cytokines p. 99, 106

type IV hypersensitivity p. 111


type IV hypersensitivity reaction p. 111

Graft-versus-host disease p. 117

type IV hypersensitivity p. 111

Multiple sclerosis p. 541

as type IV hypersensitivity p. 111

Pernicious anemia p. 381

type IV hypersensitivity p. 111

Type IV hypersensitivity p. 111

graft-versus-host disease p. 117

Type IV hypersensitivity reactions

contact dermatitis p. 489


Content Reviewers

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.

T cells are called T cells because they mature in the thymus.

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.

CD8+ killer T cells do exactly what their name implies - they kill things.

They are like silent assassins of the immune system that go after very specific targets.

In contrast, CD4+ T cells locally release cytokines, which are small proteins that can stimulate or inhibit other cells.

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.


Type IV hypersensitivity is a type of delayed-type immune response, in which the immune system responds to an antigen several hours or days after exposure. It is also known as cell-mediated hypersensitivity because tissue damage involves T cells. This can be via either CD4+ T helper cells, which help coordinate the attack, or CD8+ killer or cytotoxic T cells, which directly destroy host cells. Examples include contact dermatitis, poison ivy, tuberculin skin test, and certain drug reactions, such as allopurinol. Treatment options for Type IV hypersensitivity may include medications like corticosteroids and avoiding exposure to the triggering antigen.


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