Clonal anergy
Anergy, within the realm of
Mechanism
This phenomenon was first described in B lymphocytes by
At the cellular level, "anergy" is the inability of an
However, a small number of the body's army of lymphocytes are able to react with proteins that are normally present in a healthy body. The clonal expansion of those cells can lead to
Molecular mechanism of anergy induction in T lymphocytes
Stimulation of the
Additionally, during full
On the contrary,
Thus when an antigen is properly presented to the T lymphocytes by an antigen presenting cell (APC), which displays the antigen on its MHC II complex and which activates T cell´s costimulatory receptors, T lymphocytes undergo productive response. However, when T cells interacts with an antigen not presented by the APCs, that is very probably not the antigen that an immune response should be held against, the T cell undergoes anergy. It has also been shown that certain antigens properly presented by the APCs induce the T cell activation only weakly. This weak stimuli still activates NFAT sufficiently, however AP-1 is not, thereby the anergistic response takes place even with the costimulation.[6] Strong stimulation of
Clinical significance
Anergy may be taken advantage of for therapeutic uses. The immune response to grafting of transplanted organs and tissues could be minimized without weakening the entire immune system— a side effect of immunosuppressive drugs like
Dominant tolerance
Dominant and recessive tolerance are forms of a peripheral tolerance (the other tolerance beside peripheral is a central tolerance). Where so called recessive tolerance is associated with anergized lymphocytes as described above, in the dominant form of tolerance, specialized T-reg cells which actively ablate the immune response are developed from the naive T lymphocyte. Similarly to recessive tolerance, unopposed NFAT signalling is also important for T-reg induction. In this case, the NFAT pathway activates another transcription factor – FOXP3[9] that is a marker of T-regs and participates in their genetic program.[5][10]
Testing
The "Multitest Mérieux" or "CMI Multitest" system (Multitest IMC, Istituto Merieux Italia, Rome, Italy) has been used as a general test of the level of
Experimental approaches to study anergy
Various chemicals inducing/inhibiting described T cell signalling pathways can be used to study the anergy. The anergy in T cells can be induced by Ionomycin, the ionophore capable of raising intracellular concentration of calcium ions artificially.[citation needed]
Conversely,
References
- ^ PMID 8351512.
- ^ ISBN 0-8153-4101-6.
- ^ Burnett, D. L., Reed, J. H., Christ, D., & Goodnow, C. C. (2019). Clonal redemption and clonal anergy as mechanisms to balance b cell tolerance and immunity. Immunological Reviews, 292(1), 61–75. https://doi.org/10.1111/imr.12808
- ^ PMID 12086671.
- ^ PMID 16873058.
- ^ PMID 19307325.
- PMID 17949964.
- PMID 9914222.
- S2CID 7005085.
- PMID 20103781.
- S2CID 30195122.
- S2CID 29214452. Archived from the original(PDF) on 2011-06-11.
- PMID 9230243.
Further reading
- Jenkins MK (February 1992). "The role of cell division in the induction of clonal anergy". Immunology Today. 13 (2): 69–73. PMID 1349483.
External links
- Clonal+anergy at the U.S. National Library of Medicine Medical Subject Headings (MeSH)