HYPERSENSITIVITY REACTIONS

Innocous materials can cause hypersensitivity in certain individuals leading to unwanted inflammation damaged cells and tissues Non-proper reaction of the immune system to foreign substances Mainly harmless substances – after second or multiple exposure

An overview of hypersensitivity reactions Type I. „immediate” Type II.Type III.Type IV. „late” Antibody mediatedT cell mediated

TYPES OF ANTIBODY MEDIATED HYPERSENSITIVITY REACTIONS Fc  RIα)

TYPE I HYPERSENSITIVITY REACTION ALLERGY

SENSITISATION PROCESS

MAST CELL RESPONSE TO SURFACE FcRεI CROSSLINKING EARLY MEDIATORS Biogenic amins – histamin Enzymes – triptase, chymase, carboxypeptidase LATE MEDIATORS

The effect of mast cell degranulation varies with the tissue exposed to allergen

Systemic anaphylaxis is caused by allergens that reach the blood stream

Types of IgE-derived allergic responses SYNDROME ALLERGENSROUTE OF ENTRYRESPONSE systemic anaphylaxis drugs anti-serum peanuts intravenous (either directly or after rapid absorption) edema, increased vascular permeability tracheal occlusion circulatory collapse, death acute urticaria bug bite allergy test subcutanlocal increase in blood flow and vascular permeability allergic rhinitis pollen dust mite drops inhaledirritation and edema of nasal mucosa airway inflammation asthmaanimal fur pollen dust mite drops inhaledbronchial constriction, increased mucus production food allergynut, peanuts, fish, shellfish milk, eggs oralvomiting, diarrhea pruritis (itching) urticaria (hives) anaphylaxia (rare)

Mast cell degranulation, allergic reaction in the skin of a sensibilized individual Prick test

ImmunoCAP Specific IgE Blood Test

TYPE II HYPERSENSITIVITY IgG type antibodies bound to cell surface or tissue antigens cells expressing the antigen become sensitive to complement mediated lysis or to opsonized phagocytosis frustrated phagocytosis  tissue damage the antibody inhibits or stimulates target cell function no tissue damage (e.g. M. gravis – receptor-blocking antibodies)

MECHANISMS OF TYPE II HYPERSENSITIVITY REACTIONS

DEVELOPMENT OF DRUG SENSITIVITY I.

DEVELOPMENT OF DRUG SENSITIVITY II.

The tissue, which can not be phagocytosed, is damaged Absorbed antigen (drug) FRUSTRATED PHAGOCYTOSIS MEDIATED BY IgG TYPE ANTIBODIES Binding Opsonization Internalization Enzyme release Opsonized surface Binding Frustrated Enzyme release phagocytosis

Examples - Type II hypersensitivity Newborn haemolytic anaemia Transfusion reaction Drug-derived Haemolitic anaemia Thrombocytopenia Agranulocytosis Penicillin-based antibiotics Anti-arithmic quinidine

TYPE III HYPERSENSITIVITY Antibodies binding to soluble antigens forming small circulating immune complexes which are deposited in various tissues Depends on: Size of immune complexes Antigen-antibody ratio Affinity of antibody Isotype of antibody

THE PROCESS OF TISSUE DAMAGE CAUSED BY IMMUNE COMPLEXES Immune complexes activate the complement system, neutrophils, basophils and thrombocytes Blood vessel wall permeability Frustrated phagocytosis

Sypmptpomes caused by type III hypersensitivity reactions depend on the site of immunecomplex deposition

Arthus-reaction Localized Type III hypersensitivity Local vasculitis develops as a result of immune complex deposition Inhaled antigens (fungi, animal feces) may induce similar reaction in the lung IgG type antibody ‘Farmer lung’ and ‘piegeon breeder lung’

TYPE IV HYPERSENSITIVITY REACTION T CELL MEDIATED PROCESS MACROPHAGES ARE INVOLVED

Type IV hypersensitivity reaction Chemokines, cytokines, cytotoxins

Delayed-type (TYPE IV) Hypersensitivity

Delayed-type (Type IV) Hypersensitivity

Delayed-type hypersensitivity (DTH) (e.g., tuberculin skin test) T H 1 from a previous immunization (memory)

Tuberculin skin test Ag = antigen Mycobacterium protein (PPD) Introduction of Ag

Chemical Mediators of DTH

*a contact-sensitizing agent is usually a small molecule that penetrates the skin then binds to self-proteins, making them “look” foreign Contact Dermatitis DTH as a result of a contact-sensitizing agent*

Poison ivy Anacardiaceae (family), Toxicodendron (genus) Toxicodendron radicans or Rhus toxicodendron