Allergic Reactions (Meng)

A predictable drug reaction is related to the ___________________ actions of the drug

Pharmacologic

What are the two different types of unpredictable reactions?

-Non-immunological: non-specific, idiosyncratic, intolerance

-Immunological: allergy hypersensitivity

Drug hypersensitivity is termed as "disease following a response by the immune system to an otherwise _______________ _____________."

Innocuous antigen

True or False: There is correlation between drug hypersensitivity and pharmacological actions of the drug

False: there is no correlation with known pharmacologic actions of the drug

-Drug hypersensitivity is an unpredictable reaction

The severity of drug hypersensitivity is __________ and ____________ specific

Drug and patient

True or False: past sensitivity to drugs can predict the intensity of future reactions

False

Types I, II, and III hypersensitivity reactions are ________________-mediated

Antibody

A ________________ is a small molecule that elicits an immune reaction only when attached to a larger carrier

Hapten

Briefly explain how anti-drug antibodies are generated:

An epitope on an allergen is recognized by surface Ig on a B cell. The allergen is then internalized and degraded by the B cell, and presented to CD4 T cells via MHC 2 molecules. The activated CD4 T cell will then help the B cell differentiate into plasma cells. The new formed plasma cells will then release anti-drug antibodies

True or False: in order for anti-drug antibodies to be generated, B cells and helper T cells must recognize the same antigen

True

What are the two major parts to generating anti-drug antibodies?

1. Sensitization

2. Elicitation

Explain what occurs in the elicitation portion of generation anti-drug antibodies:

Memory B cells will capture drug-bound proteins, which will allow for rapid production of new anti-drug antibodies

_______ and _______ bridge drug allergen with unique Fc receptors on leukocytes

IgE and IgG

Does IgG or IgE have a shorter half-life?

IgE has a shorter half life, meaning the duration of the reaction would be shorter than IgG

-Reactions mediated b y IgE (Type 1) would be shorter than those mediated by IgG (Type 2 and Type 3)

IgG and IgE are produced by activated _____ cells, with help from __________ ______ cells

B, CD4 T

Type 1 hypersensitivity reactions are ______-__________________, with immediate hypersensitivity

IgE-mediated

Type 1 hypersensitivity reactions have both an ____________________ response as well as a _________-______________ response

Immediate, Late-phase

In Type 1 hypersensitivity reactions, localized exposure can manifest into ________________ reactions

Systemic

What are the primary effectors of Type 1 hypersensitivity reactions?

Basophils and Mast cells

__________ ___________ mainly reside in mucosal tissue and skin, while ________________ are found circulating in blood

Mast cells, basophils

-These are the primary effectors of Type 1 hypersensitivity reactions

These are the two effectors of Type 1 reactions

Mast cells and Basophils both contain ______________, which will release upon degranulation

Histamine

Mast cells and basophils are activated by the _______-_____________ _______________ via Fc receptors

IgE-allergen complex

Mast cells and basophils express the tetrameric _____ _____________ receptors

Fc Epsilon

True or False: the Fc Epsilon receptor has low affinity for IgE

False: these have high affinity for IgE

Explain what happens when two Fc Epsilon receptors on mast cells/basophils come into close proximity with each other

This will allow for the cross-linking of two IgEs, which can then bind to a multivalent antigen

Each allergen-(IgE)2 complex will bind how many Fc epsilon receptors on mast cells/basophils?

Two Fc Epsilon receptors

_________________ occurs when a huge amount of histamine is dumped into the body in a short amount of time

Anaphylaxis

What is the most severe systemic allergic reaction?

Anaphylaxis

-Type 1 hypersensitiivty reaction

True or False: anaphylaxis normally does not occur for a few hours after exposure to an allergen

False: anaphylaxis can occurs within minutes

True or False: Type 1 hypersensitivity reactions occur in only one phase

False: these are biphasic, meaning there are two different phases that may occur (immediate and late)

True or False: as a Type 1 hypersensitivity reaction progresses (minutes to hours), the concentration of allergen will decrease

True

In anaphylaxis, there is a large amount of __________________ released in a short amount of time

Histamine

In which portion of a Type 1 hypersensitivity reaction would eosinophils and neutrophils have a role?

These would have a role in the late phase (second phase)

-The immediate phase is dominated by histamine

Type II sensitivity reactions are _______-mediated and cytotoxic

IgG

What are the effectors of Type II hypersensitivity reactions?

Natural killer (NK) cells, macrophages, neutrophils, cells that express the FcyR

In Type II hypersensitivity reactions there is destruction of __________ and ________________

RBCs (hemolytic anemia), Platelets (thrombocytopenia)

Type III hypersensitivity reactions are ______-mediated

IgG

In Type III hypersensitivity reactions, there is formation of IgG-drug _______________ in the blood

Aggregates (Immune complexes)

-These immune complexes will then be deposited into tissues

What happens after formation of the immune complexes in Type III hypersensitivity reactions?

There will be deposition of the immune complexes into tissues, which will then activate complement proteins

Type IIII hypersensitivity reactions tend to to occur ______-_____ hours after initial exposure to the allergen

24-72

________________ is inflammation of the vasculature (vascular endothelium)

Vasculitis

-Form of Type 3 hypersensitivity reaction

-Immune complexes deposited into tissues

Type IV hypersensitivity reactions are a ______________-_________ hypersensitivity mediated by __________ cytotoxic T cells

Delayed-type, CD8

Steven-Johnson Syndrome (SJS) & Toxic Epidermal Necrolysis (TEN) are types of Type _______ hypersensitivity reactions

IV (Four)