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.

مواضيع ذات صلة

Pathophysiology of Autoimmune disease

فقر الدم المناعي بالراصات الباردة Autoimmune hemolytic anemia due to Cold agglutinin

فقر الدم الانحلالي المناعي الذاتيAutoimmune hemolytic anemia

Hypersensitivity Reactions

Autoimmune Diseases

Classification of autoimmune diseases

Immunodeficiency Diseases

Acquired Immunodeficiency Syndrome