--- module: 094-02 language: en chapter: 94 title: "Immune Development, Tolerance, Hypersensitivity, and Immunological Methods" module_title: "Hypersensitivity, autoimmunity, immune-complex disease, and transplantation" source_sha256: f98edaffdf79e334bf67c48ca0835dad59965ef73bef165ff38520d3101eb905 --- # Hypersensitivity, autoimmunity, and transplantation ## Classifying immune injury ### Type I: immediate, IgE-mediated ### Type II: antibody to cells, matrix, receptors ### Type III: soluble immune complexes ### Type IV: T-cell mediated ### Autoimmunity targets self, alloimmunity same species ## Type I hypersensitivity ### Sensitisation: IL-4 and IL-13 switch to IgE #### IgE binds high-affinity Fc epsilon receptors ### Re-exposure crosslinks IgE, degranulation ### Histamine: permeability, vasodilation, itch ### Leukotrienes: sustained bronchoconstriction ### Cytokines recruit eosinophils, late phase ### Anaphylaxis: airway oedema, leak, shock #### Intramuscular adrenaline first-line #### Antihistamines do not reliably reverse it ### Sensitisation does not prove clinical allergy #### Broad panels create false-positive labels ## Type II hypersensitivity ### IgG or IgM bind cells or matrix #### Complement, phagocytosis, cytotoxicity ### Haemolysis, thrombocytopenia, Goodpasture, pemphigus ### Antibodies can stimulate or block receptors #### Graves: TSH receptor activation #### Myasthenia: acetylcholine receptor impaired #### Maternal IgG makes neonatal disease transient ### Direct antiglobulin test: bound to red cells ### Indirect test: serum antibodies ### Binding may occur without active haemolysis ## Type III immune-complex disease ### Small complexes at antigen excess evade clearance ### Complement recruits neutrophils, damages vessels ### Serum sickness systemic, Arthus local ### Deposition: charge, size, permeability, filtration ### Complement consumption may lower C3 and C4 ### Granular deposits versus linear antibody ## Type IV hypersensitivity ### T cells rather than antibody #### Th1 activate macrophages, Th17 neutrophils ### Delayed onset: recruitment and transcription ### Contact allergens act as haptens ### Patch test delayed, prick test immediate ### Irritant dermatitis mimics allergy ### Drug hypersensitivity can use any mechanism #### Rechallenge is not a casual test ## Autoimmune disease ### Organ-specific versus systemic targets ### Autoantibodies: pathogenic, marker, incidental #### Low-titre ANA common in healthy people #### Testing follows pretest probability ### Rheumatoid arthritis #### Rheumatoid factor binds Fc, not specific #### Anti-citrullinated antibodies more specific ### Tissue injury exposes new epitopes ### Lupus sustained by interferon and poor clearance ## Vasculitis and neurological disease ### Large-vessel disease: T cells and macrophages ### Antineutrophil antibodies in some small-vessel disease ### Vessel calibre predicts organs, not cause ### Surface-receptor antibodies respond to removal ### Intracellular antigens mark tumour T-cell injury ### Serum antibody needs specificity and phenotype ## Transplantation ### Direct recognition of intact donor HLA ### Indirect recognition of donor peptides ### High precursor frequency, strong responses ### Hyperacute rejection: preformed antibodies #### Complement, thrombosis, ischaemic necrosis #### Prevented by crossmatching and screening ### Acute rejection: T-cell and antibody-mediated ### Chronic rejection: narrowing and fibrosis #### No single marker captures it ### Graft-versus-host disease: donor T cells attack #### Skin, gut, liver, marrow #### Graft-versus-leukaemia benefit ## Treatment and synthesis ### Avoid triggers, block mediators, restrain cells ### Glucocorticoids alter transcription broadly ### Biologics target cytokines, B cells, complement ### Precision reduces, never eliminates, risk ### Diseases occupy several boxes, a network