ACEM Primary
Hypersensitivity Reactions
- Excessive reaction on second exposure to antigen in sensitized individual
- Reflects imbalance between effector mechanisms of immune response and control mechanisms which usually limit these
- Both endogenous and exogenous antigens
- Associated with inheritance of susceptibility genes (HLA)
| Type of reaction | Prototypic disorder | Immune mechanism | Pathologic lesion |
| Immediate (I) = IgE mediated triggering of mast cells and subsequent accumulation of inflammatory cells at sites of Ag deposition. | Anaphylaxis Asthma | Production IgE Ab -> release vasoactive amines and other mediators from mast cells + recruitment of inflammatory cells -> vessels and smooth muscle. Mast cells: – Cytoplasmic granules containing biologically active substances Activated by cross linking of IgE Fc R, complement components – TH2 cells: Dendritic cells present antigen to TH2 -> IL-4 stimulates B cells to produce IgE -> binds FC R of mast cells On repeat exposure to allergen, mast cells release mediators: Vasoactive amines (histamine, proteases, heparin) = initial reaction in 5-30 mins Lipid mediators – Leukotrienes – vasoactive + chemotactic – Prostaglandin D2 – bronchospasm, increased mucous secretion – PAF – platelet aggregation, chemotactic, bronchospasm, histamine release, vasodilation and increased permeability Cytokines (TNF, IL-1, chemokines) = late phase reaction 2-24 hours: infiltration of eosinophils, neutrophils, basophils, monocytes and CD4+ T cells -> mucosal epithelial damage | Vasodilation Oedema Smooth muscle contraction Mucous production Inflammation |
| Antibody mediated (II) | AIHA Goodpasture syndrome | Production of IgG and IgM -> binds to normal or altered Ag on target cell or tissue -> 3 mechanisms: – Phagocytosis/lysis: cells coated with Ab attract phagocyte or cell lysis Eg. Transfusion reaction = cells from incompatible donor are opsonised by host Ab – Inflammation: deposited Ab activate complement (C3a/ C5a) which attracts leukocytes, increased vascular permeability and release pro-inflammatory substances -> N make lysosomal enzymes + ROS Eg. Glomerulonephritis – Cellular dysfunction: Ab directed at cell surface R impair or dysregulate function Does not always result in inflammation or cell damage. – Myasthenia gravis = Ab to Ach R prevent Ach binding, decreased neurotransmission and weakness – Graves disease = Ab to TSH R, hyperthyroidism | Phagocytosis/lysis of cells Inflammation |
| Immune complex mediated (III) | SLE Serum sickness | Deposition of Ag-Ab complexes -> damage at site of deposition or can circulate. Systemic – Serum sickness (horse serum for diphtheria acts at antigen causing arthritis, vasculitis and glomerulonephritis) – SLE Local – Arthus reaction whereby localised area of tissue necrosis due to acute immune complex vasculitis 3 phases: – Immune complex formation – Deposition – Medium sized complexes, Ag > Ab = most damaging – Sites of high blood filtration or fluid formation (glomerulus, synovium) – Inflammation – Complexes bind leukocytes Fc R + complement 3a – 10 days post antigen administration – Fever, urticaria, arthralgia, proteinuria | Inflammation Necrotising vasculitis (fibrinoid necrosis) |
| Cell mediated (IV) | Contact dermatitis MS T1DM RA IBD TB | Sensitised T cells 2 mechanisms: – Delayed type hypersensitivity: APC presents antigen to sensitised TH1 and TH17 cells -> release INF y/ TNF/ IL-17 and IL-22 -> macrophage activation and inflammation – Tuberculin skin test Injection of tuberculin protein (containing Ag of tubercle bacillus) in previously sensitised person -> 8-12 hours, red indurated site -> peaks 24-72 hours then subsides – GRANULOMATOUS INFLAMMATION = Persistent antigen (TB) -> perivascular infiltrate dominated by macrophages for 2-3 weeks -> form epithelioid cells -> aggregation = granuloma – Eg. Contact dermatitis – T-cell mediated cytolysis Cells display antigen on MHC I, recognised by CD8+ cells -> cell killing via perforins/ granzymes or Fas ligand inducing apoptosis – Eg. Type I diabetes (Ag on beta islet cells), MS (protein in CNS myelin) | Perivascular cellular infiltrates Oedema Granuloma formation |
Last Updated on August 20, 2021 by Andrew Crofton
Andrew Crofton
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