Hypersensitivity Reactions Gell and Coombs classification: Type I - - PowerPoint PPT Presentation

Hypersensitivity Reactions

• Gell and Coombs classification:

– Type I – IgE mediated (allergy) – Type II – Antibody-mediated cytotoxic – Type III – Immune Complex mediated – Type IV – Delayed-Type Hypersensitivity (DTH)

• Types I, II and III are “immediate”
• Type IV is delayed

Type I Hypersensitivity

• Antigens are called “allergens”
• Unknown why people get allergies, but there is a

strong genetic predisposition (called atopy)

• Hallmark is inappropriate production of IgE

against allergens that cause mast cell degranulation (see fig 15-2)

• Normally IgE/mast cell activity should be

directed against parasitic infections

Type I Hypersensitivity

• Mediators of Type I hypersensitivites

– Mast cell granule contents (early effects)

• Histamine and Heparin - ↑ vascular permeability, smooth

muscle contraction (intestines, bronchi), mucus secretion

• Chemotactic factors – attract eosinophils and neutrophils
• Proteases – mucus secretion, complement activation,

degradation of blood vessel basement membrane

– Later Effects

• Leukotrienes and prostaglandins – secreted after tissue

disruption caused by mast cell degranulation, effects are similar to histamine

• Arrival of proinflammatory eosinophils and neutrophils

Clinical Manifestations of Type I

• Systemic anaphylaxis

– Allergen gets into the blood stream – Dyspnea, ↓BP, bronchole constriction, GI and bladder smooth muscle contration, shock, death within minutes if untreated – Treatment - epinephrine

• Allergic rhinitis (hay fever)

– Inhaled allergen triggers reaction in nasal mucosa – Watery exudate from nose, eyes, upper respiratory tract, sneeezing and coughing

Clinical Manifestations of Type I

• Asthma

– Allergic asthma – due to inhaled airborne allergens (pollens, dust, fumes, etc) – Intrinsic asthma – triggered by cold, exercise – Reaction develops in lower respiratory tract – Bronchoconstriction, airway edema, mucus secretion, inflammation

• Food allergies

– Ingestion of allergen – Vomiting and diarrhea – If allergens are absorbed into bloodstream, reactions can occur where allergen deposits

• asthma-like symptoms
• Urticaria (hives, wheal & flare response)

Clinical Manifestations of Type I

• Atopic Dermatitis (allergic eczema)

– Often occurs in young children – Red skin rash – Strong hereditary predisposition

Type I Hypersensitivity

• Skin testing

– Potential allergens are injected or scratched into the skin – If the patient is allergic a wheal & flare response

• ccurs
• RIST –

radioimmunosorbent test – similar to RIA, non- invasive way to identify allergies

Type I Hypersensitivity

• Treatment

– Avoid allergen if possible – Antihistamines, or anti-prostaglandins – Hyposensitization – injections of low doses of allergen may cause a shift from IgE to IgG as the dominant antibody formed.

Type II Hypersensitivity

• Antibody-mediated Cytotoxic HS

– Antibodies (IgM or IgG) bind to cell surface

• antigens. Antigen/antibody complex may lead

to:

• Complement activation  lysis
• ADCC
• Opsonization  phagocytosis

– These are normal reactions, but when they cause unwarranted tissue damage, they are considered a hypersensitivity.

Type II Hypersensitivity

• Examples of Type II HS:

– Transfusion reactions

• To ABO blood groups
• To other RBC blood groups

– Hemolytic disease of the newborn (erythroblastosis fetalis) – Drug-induced hemolytic anemia (penicillin)

Type III Hypersensitivity

• Immune Complex Disease

– Antibody (IgG) / attaching to soluble antigen leads to complex formation – Immune complexes may deposit in:

• Blood vessel walls (vasculitis)
• Synovial joints (arthritis)
• Glomerular basement membrane

(glomerulonephritis)

• Choroid plexus

Type III Hypersensitivity

• Damage occurs due to:

– Anaphylatoxin release due to complement activation (C3a, C5a) which then attracts neutrophils, and causes mast cell degranulation – Neutrophils have trouble phagocytosing “stuck” immune complexes so they release their granule contents leading to more inflammation – Platelet aggregation also results from complement activation

• These effects are also known as the Arthus

reaction

Type III Hypersensitivity

• Localized reactions

– edema and redness (erythema) and tissue necrosis of the affected tissue – Can occur in the skin following insect bites – Can occur in the lungs

• E.g. “farmer’s lung” from inhaling particles from

moldy hay

Type III Hypersenstivity

• Generalized reactions:

– Serum sickness (following treatment with antiserum to a toxin) – Autoimmune diseases

• SLE
• Rheumatoid arthritis

– Drug reactions (penicillin) – Infectious diseases

• Meningitis, hepatitis, malaria, mono etc.

Type IV Hypersensitivity

• Delayed type hypersensitivity (DTH)

– TH cells that have been “sensitized” by an antigen develop a TH1 and (sometimes a TC response) leading to macrophage recruitment and activation. – First noticed with reaction to tuberculosis bacteria (tuberculin reaction) – Hallmarks of type IV is the large number of macrophages at the reaction site, and that it takes an average of 24 hrs to manifest after repeat exposure.