DR Medhat MRCP

Tolerance & autoimmunity :
o The immune system attacks the foreign antigens & doesn`t attack self antigens.
o Immune tolerance means lack of reaction to certain antigen ,so the body has
immune tolerance to self antigens and when there is loss of this tolerance
autoimmune disease develops.
Mechanisms that maintain self- immune tolerance of T-cells & B-cells:
a) Central tolerance : early elimination of autoreactive clones of B&T cells
during development (in BM for B-cells & in thymus for T-
cells)
b) Peripheral tolerance : elimination of autoreactive cells escaped to the
peripheral blood by the same mechanisms that makes
CD4 unreactive to self antigens.
Mechanisms of loss of immune tolerance & hence autoimmune disease :
1- Polyclonal B-cell activation : non-specific B-cell activation may contribute to
pathogenesis of SLE.
2- Cross reactivity : exposure to foreign antigen that is similar to self-AG e.g in
reactive arthritis following bacterial or viral infection.
3- Modification of self antigen : new epitopes may be generated on the self
antigen e.g in SLE where antibodies react to
neoepitopes (previously unseen epitopes) on
activated complement C1q.
DR/ MEDHAT SLEAT
2013
69