Immunotoxicology

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Immunotoxicology is a field of toxicology that studies the effects of chemical substances, which are usually of low molecular weight, on the immune system . The type of toxic effect of a certain substance is closely related to the special properties of the immune system, in particular the large number of possible cell types and their functions.

Immunotoxic effects

Immunotoxic chemical substances can either impair the immune system, one speaks of immunosuppression , or lead to a misdirected immune response, such as allergy or autoimmunity . The respective underlying molecular processes are very different and depend on the substance.

Substances with an immunosuppressive effect

Some substances impair the ability of immune cells to survive or divide, change their development ("differentiation"), or lead to decreased function of immune cells, such as decreased production of cytokines . All immune cells, i.e. H. Granulocytes , natural killer cells , T and B lymphocytes , stem cells, etc. can be affected. The exact molecular or cellular mechanism of action for most substances is not known. The induction of immunosuppression may be therapeutically necessary and desirable, e.g. B. in connection with the prevention of the immune system caused transplant rejection, or for the treatment of allergies. A number of drugs exist for this purpose.

Immunotoxic substances causing allergies

Chemical substances can form compounds with the cell's own protein structures. When these compounds get on the surface of cells, they can trigger a specific T cell response. Depending on the type of T-cell reaction, different allergic reactions (the immediate type I or the delayed type IV) can develop. Examples of this type of immunotoxic substances are urushiols , ingredients from American poison ivy , penicillin , or nickel salts. The allergic contact dermatitis in humans based on this mechanism.

Autoimmune immunotoxic substances

In principle, the immune system can also be directed against proteins of the own body, in this case one speaks of autoimmunity. A number of immunological mechanisms ensure that autoimmunity is normally prevented. T cells, whose specific receptors are directed against the body's own proteins, are eliminated immediately after their formation in the thymus . In addition, there are regulatory T cells in the immune system that can suppress immune responses. Another mechanism of immunological tolerance is the inaccessibility of autoantigens. So T cells are z. B. prevented from reaching the brain or eye, and therefore cannot drive any tissue-destructive inflammatory processes there. Chemical substances can disrupt or cancel these protective mechanisms (immunologists also call this breaking of tolerance towards self), so that an immune response develops. A number of drugs can cause allergic or autoimmune, unwanted immune reactions. The drug-induced systemic lupus erythematosus is known .

Known substances with immunotoxic effects

Testing of immunotoxic effects

The World Health Organization ( WHO) estimates that there are currently around 100,000 chemicals on the market. The majority have not been tested for their immunotoxic potential. National and transnational (e.g. the European Union) regulations stipulate immunotoxicological tests of chemicals that are sold commercially, especially in the cosmetic and medical sectors. The so-called REACH regulation of the EU has banned animal testing for cosmetic products REACH regulation since 2007.

The testing of chemicals for their immunotoxic potential takes place step by step, based on theoretical considerations and a "Weight of Evidence" analysis, in a first step tests such as changes in the blood count, pathological organ changes, clinical chemistry are recorded. Further immune tests such as impairment of cell functions in vitro or immune defects in vivo (animal experiments) can follow. For the approval of drugs and for z. B. cosmetic products exist corresponding test regulations.

Relevant guidelines

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  • Comprehensive Medicinal Chemistry II. Elsevier Verlag, 2006, ISBN 0-08-044513-6 .
  • HW Vohr (Ed.): Encyclopedia of Immunotoxicology. Springer Verlag, Heidelberg 2016, ISBN 978-3-642-54596-2 .
  • C. Esser (Ed.): Environmental Influences on the Immune System. Springer Verlag, Heidelberg 2016, ISBN 978-3-7091-1888-7 .
  • ICH S8 guideline for immunotoxicological testing of medicinal products ich.org
  • A. Widera: Highlight report: diagnostic systems for the analysis of immune functions in humans. In: Arch Toxicol. 90 (12), Dec 2016, pp. 3147-3148.
  • C. Rovida et al .: Integrated Testing Strategies (ITS) for safety assessment. In: ALTEX. 32 (1), 2015, pp. 25-40. doi: 10.14573 / oldx.1411011 .
  • T. Hartung, E. Corsini: Immunotoxicology: Challenges in the 21st century and in vitro opportunities. In: ALTEX. 30 (4), 2013, pp. 411-426.

Web links

Individual evidence

  1. ↑ ema.europa.eu
  2. ↑ ema.europa.eu
  3. ↑ ema.europa.eu
  4. ↑ ema.europa.eu
  5. ↑ Guide of the US Food and Drug Administration on immunotoxic testing of new drugs here ( Immunotoxicology Evaluation of Investigational New Drugs )