Hypersensitivity Reactions

Question 1

What immunologic agent mediates Type 1 hypersensitivity reactions?

Answer 1

Type 1 hypersensitivity reactions have an immediate response and are IgE-mediated.

Question 2

What immunologic agent mediates Type 2 hypersensitivity reactions?

Answer 2

Type 2 hypersensitivity reactions are cytotoxic and either IgG or IgM-mediated.

Question 3

What immunologic agent mediates Type 3 hypersensitivity reactions?

Answer 3

Type 3 hypersensitivity reactions are immune complex-mediated.

Question 4

What immunologic agent mediates Type 4 hypersensitivity reactions?

Answer 4

Type 4 hypersensitivity reactions have a delayed response and are cell-mediated.

Question 5

What is the mechanism of an immediate (Type 1) hypersensitivity reaction?

Answer 5

The acute phase of immediate hypersensitivity reactions occurs within one hour after exposure - usually within minutes. Mast cell degranulation releases histamine, which is the main cause of symptoms. The reaction is IgE mediated and antigen specific.

Question 6

Which enzyme may be helpful in differentiating between anaphylaxis and other similar conditions (e.g. shock)?

Answer 6

Tryptase is one of the cellular products released by mast cells when they degranulate and is therefore present in patients in anaphylaxis. Checking a tryptase level may help differentiate anaphylaxis from other conditions.

Question 7

What is the result of H1 receptor activation?

Answer 7

Activation of the H1 receptor causes the wheal and flare reaction, bronchoconstriction, and pruritus.

Question 8

What is the result of H2 receptor activation?

Answer 8

Activation of the H2 receptor causes an increase in gastric acid secretion.

Question 9

What is the result of H3 receptor activation?

Answer 9

Activation of the H3 receptor causes decreased histamine synthesis and release (negative feedback).

Question 10

What is the result of H4 receptor activation?

Answer 10

Activation of the H4 receptor creates a chemotactic pathway for eosinophils.

Question 11

When does the late phase of Type 1 hypersensitivity reactions occur?

Answer 11

The late-phase response occurs 3-12 hours after the immediate reaction. It lasts hours to days and usually has an eosinophilic inflammatory infiltrate.

Question 12

Why does the late phase of Type 1 hypersensitivity reactions occur?

Answer 12

The late-phase response is a result of the initial immediate IgE reaction stimulating the synthesis of cytokines. The probability of a late-phase response increases with the severity of the acute reaction.

Question 13

What is the mechanism of Type 2 hypersensitivity reactions?

Answer 13

Type 2 reactions occur when an IgG or IgM antibody binds to a cell receptor or fixed-tissue antigen (they are autoantibodies). The binding of the antibody results in destruction of the target cell.

Question 14

List three examples of a Type 2 hypersensitivity reaction which targets cell receptors.

Answer 14

Thrombocytopenia, autoimmune hemolytic anemia, and leukopenia.

Question 15

List two examples of a Type 2 hypersensitivity reaction which targets fixed-tissue antigens.

Answer 15

Goodpasture syndrome (targets the basement membrane component in kidneys and lungs) and Myasthenia gravis (targets the ACh receptor on muscle cells).

Question 16

What type of hypersensitivity reaction should come to mind if someone presents with vasculitis?

Answer 16

Any time you see vasculitis, you should think of a Type 3 hypersensitivity reaction.

Question 17

Type 3 hypersensitivity reactions are seen in what three broad categories of disease?

Answer 17

Vasculitis, IgG autoimmune diseases, and drug reactions.

Question 18

What is the mechanism of disease in Type 3 hypersensitivity reactions?

Answer 18

Type 3 hypersensitivity reactions occur when an antibody (usually IgG) reacts with a target antigen to form an immune complex. The immune complex then precipitates and activates complement, leading to small vessel inflammation and necrosis.

Question 19

At what Ag:Ab ratio does most immune-complex precipitation occur in a Type 3 hypersensitivity reaction?

Answer 19

Significant precipitation occurs only when there is slight excess antigen in relation to antibodies because the immune complexes at this stage are bigger and less soluble than at the start of the reaction (when they are quickly cleared), but smaller than at later stages when the immune complexes are even larger and can be quickly removed by the circulating phagocytes (macrophages). Significant precipitation usually occurs 1-2 weeks after the initiation of the antibody response as exceedingly more antibodies are produced.

Question 20

What is the pathologic hallmark skin sign in patients with a Type 3 hypersensitivity reaction?

Answer 20

Leukocytoclastic vasculitis (hemorrhagic indurated lesions.

Question 21

What type of hypersensitivity reaction is serum sickness?

Answer 21

Type 3 (immune complex-mediated).

Question 22

What is the typical clinical course of a patient with serum sickness?

Answer 22

Serum sickness is usually self-limited, and patients typically recover fully. Occasionally, corticosteroids are given.

Question 23

The tuberculin skin test is an example of which type of hypersensitivity reaction?

Answer 23

Type 4 (cell-mediated)

Question 24

What is the mechanism of Type 4 hypersensitivity reactions?

Answer 24

Previously sensitized T cells interact with an antigen, causing an inflammatory reaction. The reaction peaks in 24-72 hours - hence the common name: delayed-type hypersensitivity.