Autoimmunity occurs when the immune system fails to distinguish self from non-self and attacks the body's own tissues. There are several proposed mechanisms for how immune tolerance is broken, including immunological, genetic, and microbial factors. Common autoimmune diseases are either organ-specific, where antibodies form against a specific organ like the thyroid, or systemic, where multiple antibodies attack various tissues throughout the body.

1. AUTOIMMUNITY
• Autoimmunity is a state in which the body’s immune system fails to distinguish
between ‘self’ and ‘non-self’ and reacts by formation of autoantibodies against
one’s own tissue antigens.
• In other words, there is loss of tolerance to one’s own tissues; autoimmunity is
the opposite of immune tolerance.
PATHOGENESIS (THEORIES/ MECHANISMS) OF AUTOIMMUNITY
• The mechanisms by which the immune tolerance of the body is broken causes
autoimmunity. These mechanisms or theories of autoimmunity may be
immunological, genetic, and microbial, all of which may be interacting.
1. Immunological factors
• Failure of immunological mechanisms of tolerance initiates autoimmunity.
These mechanisms are as follows:
i) Polyclonal activation of B cells. B cells may be directly activated by stimuli such as
infection with microorganisms and their products leading to bypassing of T cell
tolerance.

2. ii) Generation of self-reacting B cell clones may also lead to bypassing of T cell
tolerance.
iii) Decreased T suppressor and increased T helper cell activity. Loss of T
suppressor cell and increase in T helper cell activities may lead to high
levels of auto-antibody production by B cells contributing to auto-
immunity.
iv) Fluctuation of anti-idiotype network control may cause failure of
mechanisms of immune tolerance.
v) Sequestered antigen released from tissues. ‘Self-antigen’ which is
completely sequestered may act as ‘foreign-antigen’ if introduced into the
circulation later. For example, in trauma to the testis, there is formation of
anti-sperm antibodies against spermatozoa; similar is the formation of
autoantibodies against lens crystallin.

3. 2. Genetic factors.
• There is evidence in support of genetic factors in the pathogenesis of
autoimmunity as under:
i) There is increased expression of Class II HLA antigens on tissues involved in
autoimmunity.
ii) There is increased familial incidence of some of the autoimmune disorders.
3. Microbial factors.
• Infection with microorganisms, particularly viruses (e.g. EBV infection),
and less often bacteria (e.g. treptococci, Klebsiella) and mycoplasma, has
been implicated in the pathogenesis of autoimmune diseases.

4. TYPES AND EXAMPLES OF AUTOIMMUNE DISEASES
• Depending upon the type of autoantibody formation, the autoimmune diseases
are broadly classified into 2 groups:
1. Organ specific diseases.
• In these, the autoantibodies formed react specifically against an organ or
target tissue component and cause its chronic inflammatory destruction.
• The tissues affected are endocrine glands (e.g. thyroid, pancreatic islets of
Langerhans, adrenal cortex), alimentary tract, blood cells and various other
tissues and organs.
2. Organ non-specific (Systemic) diseases.
• These are diseases in which a number of autoantibodies are formed which
react with antigens in many tissues and thus cause systemic lesions.