Type I. „immediate” Type II.Type III.Type IV. „late” Antibody mediatedT cell mediated AN OVERVIEW OF HYPERSENSITIVITY REACTIONS

TYPES OF ANTIBODY MEDIATED HYPERSENSITIVITY REACTIONS Fc  RIα)

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

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

EXAMPLES - TYPE II HYPERSENSITIVITY Newborn haemolytic anaemia Transfusion reaction Hyperacut allograft rejection Drug-derived Haemolitic anaemia Thrombocytopenia Agranulocytosis Penicillin-based antibiotics Anti-arithmic quinidine Goodpasture syndrome (kidney, basal membrane - collagen type IV) Pemphigus vulgaris (mucosal bubbles)  against desmosomal antigens, interruption of epidermal and mucosal connections, acantolysis (desintegration into single cells) Myasthaenia gravis (anti-acetyl-choline receptor antibodies) Graves-Basedow-Flajani disease (anti-TSH-receptor antibodies)

DEVELOPMENT OF DRUG SENSITIVITY I.

DEVELOPMENT OF DRUG SENSITIVITY II.

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 ‘Farmers lung’ and ‘piegeon-breeder’s lung’

Facial, malar "butterfly" rash with characteristic shape across the cheeks. Discoid lupus erythematosus (DLE) involves mainly the skin, it is relatively benign compared to systemic lupus erythematosus (SLE). In either case, sunlight exposure accentuates this erythematous rash. A small number (5 to 10%) of DLE patients go on to develop SLE (usually the DLE patients with a positive ANA). Here is a more severe inflammatory skin infiltrate in the upper dermis of a patient with SLE in which the basal layer is undergoing vacuolization and dissolution, and there is purpura with RBC's in the upper dermis (which are the reason for the rash). MANIFESTATION OF TYPE III HYPERSENSITIVITY IN LUPUS ERYTHEMATOSUS

One of the feared complications of the systemic autoimmune diseases is renal failure. This is most likely to occur in SLE. Here is a glomerulus in which the capillary loops are markedly pink and thickened such that capillary lumens are hard to see. This is lupus nephritis. RENAL FAILURE IN IMMUNECOMPLEX DISEASES Glomerulus of a healthy individual. Relatively wide spaces between capillary loops.

TYPE IV HYPERSENSITIVITY REACTION T CELL MEDIATED PROCESS

TYPE IV HYPERSENSITIVITY REACTION

DELAYED-TYPE (TYPE IV) HYPERSENSITIVITY

T H 1 from a previous immunization (memory) DELAYED-TYPE HYPERSENSITIVITY (DTH) DELAYED-TYPE HYPERSENSITIVITY (DTH) (e.g. tuberculin skin test)

Tuberculin skin test Ag = antigen Purified protein derivate (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 DTH as a result of a contact-sensitizing agent* CONTACT DERMATITIS

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

CELIAC DISEASE

Delayed-type hypersensitivity is mediated by T cells