Themes > Science > Life Sciences > General Biology > Immunology > The Immune System & Disease > Autoimmunity > Mechanisms of autoimmune pathology

Although in many cases the precise combination of pathogenetic mechanisms is not understood, there are three general types of mechanism which it is important to distinguish.
  • Direct antibody mediated effects
  • T cell mediated effects (cellular immune)
  • Immune complex mediated effects

Direct antibody mediated pathology

We have already seen one example in Graves' disease where stimulatory antibodies dysregulate thyroid function. A counter effect can also be seen as in Myasthenia Gravis. In this disease, autoantibodies to the Acetylcholine receptor block neuromuscular transmission from cholinergic neurons by blocking the binding of acetylcholine and by causing downregulation (degradation) of its' receptor. Rheumatic fever is an example of direct tissue pathology following antibody binding.

Click here to see a diagram showing the mechanism of pathology in Myasthenia Gravis


T cell mediated damage

This term implies that the recognition of autoantigen by T cells leads to tissue destruction without requiring the production of autoantibody. There are a number of ways this can come about:

  1. Direct T cell cytotoxicity via CD8+ CTL
  2. Self-destruction of tissue cells induced by cytokines, eg, TNFa
  3. Recruitment and activation of macrophages leading to bystander tissue destruction
  4. Induction of target tissue apoptosis by the T cell membrane protein FasL
In most cases we do not know what the relative contribution of these factors is, though mechanism 4 would have to be confined to those tissues which constitutively express the 'death' protein Fas or which express it as a consequence of inflammation. See 'Animal model's of autoimmunity' (below) for further discussion.

Immune-complex mediated pathology

Immune-complexes are frequently implicated in autoimmune pathology. Systemic diseases such as SLE and vasculitis almost certainly result from autoantibody-antigen complexes and their consequences. Certain organs are especially sensitive to immune complex deposition particularly the kidney. SLE patients possess a wide variety of autoantibodies to both cytoplasmic and nuclear antigens. The presence of IgG anti double- stranded DNA is characteristic of this condition (Note: IgM anti-ds DNA is NOT pathogenic). Two significant facts point to the role of immune complexes in SLE. First, patients demonstrate significant depletion of complement (C3) and neutrophils resulting from activation by the complexes. Second, complement deficiencies which impair IC clearance (C1,C2 or C4, see lecture 10) are very strong predisposing factors for SLE.


Information provided by: http://www-immuno.path.cam.ac.uk