Hypersensitivity

What are hypersensitivity reactions?

Exaggerated immune responses to a harmless antigen that can cause inflammation, tissue injury, disease, or death and involve the acquired immune system.

Do hypersensitivity reactions depend on the antigen itself or the host response?

The host response.

What is sensitization in hypersensitivity?

Prior exposure to antigen that leads to development of an immune response.

Can hypersensitivity antigens be exogenous or endogenous?

Yes, they can be exogenous (environmental) or endogenous (cell surface/soluble).

What are allergens?

Antigens that trigger allergic reactions.

Which hypersensitivity types are considered 'allergic' reactions?

Type I (immediate) and Type IV (delayed).

What factors are used to differentiate Types I-IV?

Response time, whether antibody is involved, whether complement is involved, and which cells mediate the response.

What antibody class mediates Type I hypersensitivity?

IgE.

How fast does Type I hypersensitivity occur after exposure?

Typically 2-30 minutes.

Which T-helper subtype is involved early in Type I development?

CD4+ Th2 cells.

What is the key B-cell class switch in Type I hypersensitivity?

Switching to IgE production.

Where does IgE bind after it is produced?

Fc portion binds to mast cells in tissues and basophils in the bloodstream.

Why can mast cells/basophils bind lots of IgE?

They have large numbers of receptors for the Fc portion of IgE.

What is the 'sensitization phase' in Type I?

When IgE becomes bound to mast cells/basophils and remains dormant until re-exposure.

What triggers mast cell/basophil activation in Type I?

A second exposure where allergen binds IgE on these cells.

What is the immediate consequence of mast cell/basophil activation?

Release of mediators that drive clinical symptoms.

What is the overall range of Type I severity?

From mild localized reactions to life-threatening systemic anaphylaxis.

List the main Type I clinical manifestations.

Allergic rhinitis, allergic asthma, atopic dermatitis, urticaria, GI reactions, systemic anaphylaxis.

What are common symptoms of allergic rhinitis?

Runny nose, sneezing, watery eyes.

What kinds of allergens commonly trigger allergic rhinitis?

Pollens, molds, animal dander, dust mites.

What are typical allergic asthma symptoms?

Coughing, wheezing, shortness of breath.

What is atopic dermatitis associated with clinically?

Itchy red rash triggered by irritants/allergens/foods.

What is urticaria described as?

A 'wheal and flare' reaction with widespread itchy pale areas surrounded by erythema.

What symptoms are typical of GI allergic reactions?

Nausea, vomiting, abdominal pain, diarrhea.

What is systemic anaphylaxis?

A potentially life-threatening whole-body allergic reaction.

What are common triggers of systemic anaphylaxis?

Foods (shellfish, peanuts), antibiotics (penicillin), and venom (bees/wasps).

What are key anaphylaxis symptoms listed?

Hypotension, shock, airway obstruction.

What is the urgent treatment for anaphylaxis?

Epinephrine injection.

How does epinephrine help in the lungs?

Binds beta-adrenergic receptors and relaxes smooth muscle to open the airways.

How is Type I allergy testing categorized?

In vivo methods and in vitro methods.

What is the main in vivo test approach?

Direct skin testing.

Why is skin testing emphasized?

It is the least expensive and most specific type of testing.

What do in vitro allergy tests typically evaluate?

Levels of components of the immune response, especially total IgE.

What does RIST measure?

Total IgE and does not identify a specific allergen.

What does RAST measure?

Allergen-specific IgE using panels of inhalants and foods.

Which test has more clinical value for identifying a specific allergy?

RAST.

What is the first basic management step for Type I reactions?

Avoidance of the allergen.

What medication classes are listed to block allergic responses?

Antihistamines, theophylline, epinephrine, cromolyn sodium, corticosteroids.

What is immunotherapy/desensitization?

Giving increasing amounts of allergen over time to induce tolerance.

What antibodies are involved in Type II hypersensitivity?

IgG and IgM.

What is the basic mechanism descriptor for Type II?

Antibody-dependent, complement-mediated cytotoxic reactions.

Name Type II clinical manifestations.

Transfusion reactions, hemolytic disease of the newborn, hemolytic anemias.

What is the classic ABO example given?

A Type B recipient receiving Type A blood leads to hemolysis.

What is the key test for Type II hypersensitivity?

Direct antiglobulin test (DAT).

What does the DAT detect conceptually?

RBCs sensitized in vivo with Ig.

What indicates a positive DAT in the lab?

Agglutination after mixing patient RBCs with anti-human globulin.

What is Type III hypersensitivity?

Immune complex deposition in tissues/blood vessel walls with IgG or IgM.

What kinds of antigens can be involved in Type III?

Foreign proteins, infectious organisms, or self-antigens.

What is the first major step in Type III pathogenesis?

Soluble antigen binds soluble antibody to form immune complexes.

What normally happens to immune complexes?

They are cleared by phagocytic cells.

What happens when the immune system is overwhelmed?

Complexes deposit in tissues.

What drives tissue injury after deposition in Type III?

Complement binding/activation leading to inflammation.

How do you test for Type III hypersensitivity?

Look for immune complex deposition in tissues using immunohistochemistry.

Is antibody involved in Type IV hypersensitivity?

No.

What cells mediate Type IV hypersensitivity?

CD4+ Th1 T cells and phagocytes.

What is the typical timing of Type IV reactions?

Delayed; usually 2-3 days after exposure.

What happens 1-2 weeks after initial antigen contact in Type IV?

Antigen is processed and presented to Th1 cells.

What happens on subsequent exposure in Type IV?

Memory TDTh cells release cytokines that attract monocytes.

What is contact dermatitis?

A Type IV skin reaction to agents like detergents or poison ivy.

How do allergens act in contact dermatitis?

As haptens that bind skin proteins and activate memory T cells.

When does the rash of contact dermatitis usually appear?

Hours to days later, usually 2-3 days.

What is hypersensitivity pneumonitis?

A Type IV reaction from inhaled allergens, often occupational.

What is the Mantoux test used for?

Screening for M. tuberculosis exposure.

What does a positive Mantoux test suggest?

Exposure to TB or prior BCG vaccination.

What is the main test for allergic contact dermatitis?

Allergen patch testing.