Immunologic Tolerance

Immunologic tolerance is a state in which an individual is incapable of developing an immune response to specific antigens. Self-tolerance refers to lack of responsiveness to an individual’s antigens. Tolerance can be broadly classified into two groups: central and peripheral tolerance.

i) Central tolerance

-  This refers to clonal deletion where immature clones of T and B-lymphocytes that bear receptors for self-antigens are eliminated from the immune system during development in central lymphoid organs. T cells that bear receptors from self-antigens undergo apoptosis within/ during the process of T-cell maturation.   

ii) Peripheral tolerance 

1. Clonal deletion by activation–induced cell death. The engagement  of Fas by Fas ligand co-expressed on activated T-cells dampens the immune response by inducing apotosis of activated T-cells ( Fas mediated apoptosis)

2. Clonal anergy: Activaton of Ag specific T-cell requires two signals

a). Recognition of peptide Ag  wtih  self-MHC molecules

b). Co-stimulatory signals such as CD 28 must bind to their ligand called B7-1 and B7-2 on antigen presenting cells (APC) and if the Ag is presented by cell that do not

bear CD 28 ligand /i.e B7-1 or B7-2/ a negative signal is delivered and the cell becomes anergic. 

iii). Peripheral suppression by T- cell suppressor. 

•  There are some evidence that peripheral suppression of autoreactivity may be mediated in part by the regulated secretion of cytokines. 

•  The CD+ T cells of the TH2 type have been implicated in mediating self-tolerance by regulating the functions of pathogenic TH1 type cells. Cytokines produced by TH2 T cell can down regulate autoreactive CD+Th1 by elaborating IL-4, IL-10 and TGF-B. 

When normal tolerance of the self antigens by the immune system fails, autoimmune diseases result.

References

Bezabeh ,M. ; Tesfaye,A.; Ergicho, B.; Erke, M.; Mengistu, S. and Bedane,A.; Desta, A.(2004). General Pathology. Jimma University, Gondar University Haramaya University, Dedub University.