Hypersensitivity Type III and IV

Classification of Hypersensitivity TypeMechanismExample I IgE mediatedSystemic anaphylaxis eg peanut allergy Asthma IIAntibody mediatedHaemolytic disease of the newborn IIIImmune complex mediated Arthus reaction Glomerular nephritis IVCell mediated (delayed) Contact dermatitis Anaphylactic hypersensitivity Cytotoxic hypersensitivity Immune complex hypersensitivity Cell-mediated hypersensitivity

Type III Hypersensitivity (Immune complex mediated) Caused by IgM or IgG Abs against soluble antigens. Ab/Ag immune complexes normally removed effectively. In these reactions complexes that persist are deposited in the circulation or tissue and cause inflammation. Frequent complication in autoimmune disease.

3 Basic Categories Cause1) Persistent Infection 2) Autoimmunity3) Inhaled Antigen AntigenMicrobialSelf-antigenMould plant or animal antigen SiteKidney and infected organs Kidney, joints and skin Lung

MECHANISMS IN TYPE III HYPERSENSITIVITY Complexes interact with basophils and platelets to induce release of vasoactive amines. Macrophage stimulation results in cytokine release (TNFα IL-1). Complement activation and inflammation.

MECHANISMS IN TYPE III HYPERSENSITIVITY

Experimentally induced Type III hypersensitivity Immune complex deposition in the skin and resultant pathology is known as the Arthus reaction

TYPE IV Hypersensitivity Delayed type hypersensitivity (DTH) Typically mediated by T H 1 cells and/or macrophages which produce and respond to cytokines including TNFα and IFNγ Can be shown experimentally by transferring T cells between animals.

Delayed type hypersensitivity DTH Kumar et al. Robbins and Cotran Pathologic Basis of Disease. Elsevier 2005

3 BASIC TYPES 1- Contact hypersensitivity48-72 hours 2- Tuberculin reaction48-72 hours 3- Granulomatous reaction 21 days

Contact hypersensitivity Characterised by inflammatory reaction in the skin following contact with an allergen

ANAPHYLAXIS An immediate, severe, systemic hypersensitivity or allergic reaction, sometimes fatal, usually characterised by at least one or other of the following symptoms, respiratory difficulty, hypotension or circulatory failure. Generalised urticaria and tissue swelling also common. Mediated by IgE antibodies and Mast cells Immunologically disease. ‘Type One hypersensitivity’

Common causes of anaphylaxis Foods Serum/vaccines Bee and wasp stings Drugs Latex rubber - gloves

Foods commonly causing anaphylaxis Peanuts Tree nuts (eg. brazil nut, almond, hazlenut) Fish Shellfish Egg Milk Sesame

Drugs causing anaphylaxis Antibiotics (especially penicillin) Intravenous anaesthetic drugs Aspirin Non-steroidal anti-inflammatory drugs

Features of Anaphylaxis Erythema itching Urticaria Asthma Rhinitis Conjunctivitis Nausea, vomiting, abdominal pain Fainting, lightheadedness Collapse Lose of consciousness Hypotension/reduced blood pressure Circulatory/heart failure

Urticaria Raised, erythematous intensely itchy skin eruption caused by IgE-mediated histamine release from mast cells. Causes: DrugsFood allergens penicillinEnvironmental allergens cephalosporinsInsect bites latex

Is this allergy? “Please see this patient who is: obviously allergic to something clearly having allergy-like episodes......presumably to something he/she is eating but can’t tell what he/she is allergic to.”

Case 1 Clinical diagnosis “oral allergy syndrome” allergy to birch pollen causing symptoms on exposure to cross-reacting allergens in a variety of fruits (particularly peach, pear, apple and plum) other plant-derived foods are sometimes involved, as in this case Tests skin prick testing showed a very strong response to birch pollen. Strong responses were also obtained to hazel nut, almond, carrot and celery. Extracts of the relevant fruits gave negative results. IgE results were: –total 52.4 –birch pollen 22.3 –apple 1.01 –carrot 1.3 –celery 0.8(peach, pear and plum were negative)

The End