Theories of

Autoimmunity
Autoimmunity is
Autoimmunity a problem of self/non-self
discrimination.
 Polyclonal
Activation
Signal delivered to B- or T-cells by a
mitogen or superantigen released from a
microorganism  polyclonal activation.
 Cryptic Antigen
Hypothesis
Some self-antigens are sequestered from
immune system. Release of antigens due to injury
or infection stimulates pre-existing anti-self
lymphocytes, (e.g mumps Antibodies
v.spermsterilityrelease of lens crystallin
proteinsympathetic ophthalmia.
 Somatic mutation
Mutation in Ig V-gene could convert anti-
non-self receptor into anti-self receptor, (e.g
mouse myeloma cell line secreting anti-
phophoryl choline converted to anti-DNA as a
result of a point mutation.
 Helper T - cell By - pass
theory
Anti-self B-lymphocytes may be unable to
respond because anti-self helper t-cells
deleted or supressed. Regulation by-passed if
stimulus delivered by helper t-cells which
recognize a foreign epitope associated with a
self epitope on same mol. Or particle.
 Regulatory T - cells
Alpha-self Ls. Suppressed by Tr –Ls; AIR =
defect in Tr?
 Danger Theory
Abandons idea of self-non-self,
discrimination as central tenet of immunology.
Proposes anti-self B and T-cells are always
present.
Summary
• Self reactive B-cells & T-cells are normally present but anergic.
•
• Several factors can induce an AIR:-
•
• Genetic
•
• Tissue damage & release of cryptic ag
•
• Somatic mutation in Ig V-genes
•
• Ag mimicry
•
• Tr defects
•
• Danger signals
•