Immunology Unit 4- Hypersensitivities

Hypersensitivity:

Immune response which harms the host.

May occur when:

Responses to foreign antigens become deregulated or uncontrolled.

Responses are directed against self antigens (autoimmunity).

Type I Immediate Hypersensitivity:

Cell bound antibodies react with antigen to release active substances.

Type II Antibody-Mediated Diseases:

Free antibodies react with antigens on cell surface.

Type III Immune Complex-Mediated Diseases:

Antibody reacts with soluble antigen complexes precipitate in tissues.

Type IV T-Cell Mediated (Delayed) Diseases:

Sensitized T cells responsible for symptoms.

Immediate Type Hypersensitivity:

Antibody mediated = Types I, II and III.

Symptoms develop within minutes to hours.

Delayed Type Hypersensitivity:

Cell-mediated = Type IV.

Symptoms occur 24 to 48 hours after contact with antigen.

Type I Immediate (Anaphylactic):

Symptoms appear shortly after exposure to antigen.

Examples: Hay fever, asthma, hives, food allergies, anaphylactic shock.

Atopic Antigens:

Atopic antigens (AKA allergens) trigger the formation of IgE.

Atopy: Inherited tendency to response to naturally occurring allergens with continued production of IgE.

Evidence for HLA DR2, DR4, DR7.

30% have some type of allergic symptoms.

What are key participants of Type I?

Atopic individual- Person that usually can make increased amounts of IgE in spite of small amount of antigen.

IgE (old name reagin)- Th2 regulate IgE production.

Mast cell/basophil.

What are primary mediators?

Stored in granules and released at mast-cell activation.

Histamine.

Skin manifestations, smooth muscles contractions, increased vascular permeability.

Other factors also released.

Wheal:

Forms at the site as fluid leaks under the skin.

Is Asthma a Type I Hypersensitivity?

Yes.

Secondary mediators:

Formed after the mast cell undergoes degranulation.

Prostaglandins: Mimics effects of histamine.

Leukotrienes: Some act like histamine, but more potent.

Cytokines: Induce local inflammation (leukocyte recruitment).

Platelet-Activating Factor: Acts on platelets, PMNs, eosinophils, smooth muscles, and vasculature.

Systemic Reactions:

Anaphylaxis

Anaphylaxis:

Systemic reaction. Most severe type of response.

Clinical Signs: Bronchospasms, swelling, urticaria, diarrhea and or vomiting and shock.

Local Reactions:

Rhinitis: Sneezing, nasal congestion, itching of eyes and nose.

Asthma: Recurrent airway obstruction; breathlessness.

Food allergies: Dye to various foods (cow’s milk, peanuts, eggs)

Symptoms vary.

What are the treatments for systemic reactions?

Epinephrine, Hyposensitization: Allergy shots to build up to IgG/T cell mediated suppression.

Recombinant anti-IgE- Omalizumab.

RIST (Radioimmunosorbent test):

For Total IgE. Competitive test. Sandwich EIA. Interpretation depends on patient and family history.

Elevated IgE may indicate allergy or other conditions such as parasite, genetic disease.

RAST (Radioallergosorbent test):

For level of specific IgE. An ELISA test, Microarray test, approaching sensitive of skin testing.

Type I Overview:

Mechanism of Action: IgE stimulated by antigen; binds to mast; release of chemicals.

Recognize Mediator’s Name:

Primary- histamine;

Secondary- Prostaglandins, leukotrienes, platelet activating factor and cytokines.

Symptom/diseases: Wheal and flare, asthma, anaphylaxis, skin eruptions.

Testing: Skin, RIST (total IgE) and RAST (specific IgE)

Type II Antibody-Mediated Hypersensitivity:

Disease caused by: Antibodies (IgG or IgM) binding to cell antigens or tissue antigens and inducing inflammation.

What are some examples of Type II Hypersensitivity?

Transfusion reaction, hemolytic disease of the newborn, Autoimmune hemolytic anemia.

Hemolytic Disease of Newborn:

Mother exposed to baby blood group antigens.

Mother makes IgG antibodies- cross placenta and destroy fetal red blood cells.

Autoimmune Hemolytic Anemia:

Antibodies to self antigens.

Cold auto agglutinins.

Warm autoimmune hemolytic anemia.

Idiopathic autoimmune hemolytic anemia.

Autoimmune or idiopathic thrombocytopenic purpura (ITP).

Cold Autoagglutinins:

Usually IgM against I/i blood group.

May be seen in certain infections, cancers and autoimmune diseases. Adverse reactions seen when person exposed to cold.

Autoimmune Hemolytic Anemia:

IgG responsible. Associated with certain infections, leukemia and drugs.

Idiopathic autoimmune hemolytic anemia: Underlying cause is unknown.

Autoimmune or idiopathic thrombocytopenic purpura (ITP):

Mechanism: Antibodies formed to platelets which are destroyed. May occur after certain infections and drug treatment- occurs mainly in children following respiratory viral illness.

Goodpasture’s Syndrome:

Antibody to antigens in kidney- causes glomerulonephritis.

Hasimoto’s Disease:

Antibody to thyroid.

Myasthenia Gravis:

Antibody to acetylcholine receptors. No muscle contraction.

Insulin-dependent diabetes mellitus:

Antibody to beta cells of pancreas.