Answer
Events can result in autoimmune disease:
1- Release of hidden or sequestrated antigens
2- escape of tolerance at cell level
3- altered antigen
4- diminished suppressor T cells
5- genetic predisposing
Work Step by Step
Possible Mechanisms Involved in the development
of Autoimmunity
I- Release of hidden or sequestered antigens
- the best examples of these are sperm antigens & lens
antigen of the eye.
- Sperm can be shown to aquire an antigen during
maturation which is absent from the immature germ
cells, when such antigens enter the circulation, they
elicit immune reactions.
- Orchitis in man is a rare complication of mumps
infection in which it is assumed that the virus
damages the basement membrane barrier of the
seminefrous tubules & the cells of the immune
system are thus allowed entry to initiate an immune
response.
- as for the lens antigen, it was found that somtimes
the extraction of a lens for cataract is followed by
inflammatory changes in the retained lens.
II- Escape of Tolerance at Cell Level
- unresponsiveness to a " self " antigen may be
maintained by tolerance at the T cell level.
- such tolerance may be terminated by cross reaction
i.e. when the host responds to antigens against the
cross-react with tolerated " self " antigen.
- in the colon an antigen exists, extractable from even
sterile fetal colon, which is similar to apolysaccharide
antigen present in Escherichia coli 014.
- it is conceivable that the inflammatory condition
of the colon known as Ulcerative Colitis , in which
anti-colon antibodies are found is due to an immune
reaction initiated by the cross-reacting bacterial
antigen .
- similarly group A beta hemolytic streptococci , which
are closely associated with rheumatic fever, have
an antigen in common with a human heart antigen ,
anti-heart antibody is found in just over 50% of
patients with rheumatic heart lesions.
- again nephritogenic strains of type 12 group A
streptococci carry surface antigens similar to those
found in human glomeruli & infection by these
organisms has been associated with the
development of acute glomerulo-nephritis.
III- Altered Antigen
- drugs can act as haptens, which bind to tissue proteins
- the resulting complex may be antigenic & result in
an immune reaction which damages cells coated
with the drug.
- Examples of this are a metabolic breakdown product
of the drug Methyldopa used in treatment of
hypertension & a breakdown product of penicillin,
each of which can bind to the surface of cells.
- the immune response generated by these
drug-altered cells can result in hemolysis of the
affected cells.
IV- Diminished Suppressor T Cell Function
- in normal immune regulation, suppressor T cells
may limit an immune response to " self " antigens.
- if suppressor T cell function decreases, antibodies
to " self " antigens may be formed ( e.g. an antibody
to normal IgG ).
- such antibody occurs in complex forms in joints.
V- Genetic Predisposition
- there is a familial incidence of autoimmune diseases
.
- most of them appear to be associated with certain
major histocompatibility complexes.
- for example
rheumatoid arthritis is associated with DR4
thyroiditis with DR5
multiple sclerosis with DR2
& systemic lupus ( SLE ) with DR3.
