Type II Hypersensitivity

Overview
  • Type II Hypersensitivity is one of the basic mechanisms by which immune-mediated injury to host tissues can occur. The reaction occurs due to direct binding of antibody to host tissues resulting in either functional derangement of the tissue or inflammatory damage.
Pathogenesis
  • Overview
    • Binding of antibody to host tissues can be due to a number of etiologies. Once binding does occur, the antibody can cause a number of pathogenic outcomes.
  • Antibody Binding
    • Antibodies which bind self-antigens, also known as auto-antibodies, may be produced by auto-reactive B-cells which escaped normal processes of negative selection during B-cell Development as mentioned in Autoimmune Disease. Alternatively, administration of certain drugs may adsorb onto host proteins, generating novel antigenic epitopes that are recognized by normally selected B-cells which subsequently become activated and produce antibodies that bind drug-host protein complex.
  • Complement Activation
    • Recall that cross-linked antibodies normally activate the Classical Pathway of the Complement Cascade. This results in the generation of the membrane-disrupting "Membrane Attack Complex" or causes opsonization of the material with C3 which recruits other immune cells to phagocytose the opsonized material. When antibodies target host cells, complement activation can cause direct injury to the host cells as well as induce potent inflammation and phagocytic destruction of host tissue
  • Antibody-mediated Cell-mediated Cytotoxicity (ADCC)
    • Once cross-linked onto antigen, the Fc Region of antibody normally recruits a number of phagocytic immune cells such as macrophages and neutrophils which are then activated to phagocytose the opsonized material. When antibodies target host membranes this can result in substantial inflammation and phagocytic destruction of host tissues.
  • Antibody-mediated Cellular Dysfunction
    • Binding of antibodies can frequently disrupt the normal functioning of the bound protein. If the host protein which the antibody targets has an important regulatory or enzymatic function, the protein's function can become substantially deranged, resulting in dysregulation of the host tissue.
Clinical Consequences
  • Overview
    • The clinical consequences of Type II Hypersensitivity largely depend on which host tissue or protein is targeted and how the antibody causes damage. A few examples are given below and organized by the primary mechanism of immune damage although please refer to interlinks as well.
  • Complement Activation and ADCC
  • Antibody-mediated Cellular Dysfunction